Mental Health Challenges and Psychosocial Impact of Rare Diseases in Children and Adolescents -A Systematic Review

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New This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9253757/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Aim This systematic review aims to explore the psychosocial impact and mental health challenges of childeren and adoloscents with rare diseases (RDs) and their families. It examines their daily challenges, emotional distress, coping mechanisms, and resilience strategies while identifying systemic gaps in care and support. Methods The review adhered to PRISMA guidelines, employing a comprehensive search of databases; Google Scholar, PubMed and PsycINFO. Studies were selected based on predefined criteria and appraised for quality using the Mixed Methods Appraisal Tool (MMAT). Both qualitative and quantitative studies were included, focusing on mental health challenges, caregiver stress, coping mechanisms, and resilience strategies. Results Children and adolescents with RDs face significant emotional distress, including anxiety, depression, and a diminished quality of life, which are exacerbated by physical limitations, frequent hospitalizations, and social exclusion. Meanwhile, their primary caregivers endure profound emotional and financial burdens, compounded by the demands of advocacy roles and navigating fragmented care systems. Although families adopt various coping mechanisms, such as peer support and creative outlets like art therapy, systemic gaps in psychosocial support and access to interdisciplinary care remain prevalent. Conclusion The findings underscore the need for integrated, family-centred care models that address the multifaceted challenges of living with RDs. By fostering holistic medical, psychological, and social support systems, these models can enhance resilience, reduce the psychosocial burden, and improve the overall quality of life for children with RDs and their care Rare Diseases Child Adolescent Mental Health Caregiver Burden Quality of Life Figures Figure 1 Figure 2 Introduction Rare Diseases (RDs) are defined differently globally; in the European Union, a disease is considered rare if it affects fewer than 1 in 2,000 individuals, whereas in the United States, one RD affects fewer than 200,000 people nationwide Kole and Faurisson (2009). Collectively, RDs impact an estimated 300 million individuals worldwide, spanning over 6,000 distinct conditions that encompass genetic, infectious, degenerative, and proliferative disorders (Nguengang Wakap et al. 2019). Approximately 80% of RDs are genetic, and roughly 70% manifest in early childhood, requiring lifelong, multidisciplinary care (European Commission, 2024). The heterogeneous nature and rarity of these conditions frequently result in limited awareness among healthcare providers, leading to prolonged diagnostic delays, often described as the "diagnostic odyssey" (Witt et al. 2023). Such delays significantly impact patients and families emotionally, often involving consultations with multiple specialists before receiving accurate diagnoses (Ferreira 2019). Children and adolescents with RDs commonly experience significant mental health symptoms and psychosocial challenges, including anxiety and depressive symptoms, which are closely linked to chronic physical symptoms, frequent hospitalisations, and physical restrictions imposed by their conditions (Belzer et al. 2022). These physical limitations combined with social stigma, intensify feelings of isolation, negatively impacting self-esteem and increasing social withdrawal (Nevin et al. 2023). This psychological burden is compounded by the limited availability of specialised mental health services, despite evidence that early psychosocial interventions significantly improve mental health outcomes (Richardson et al. 2024). The profound psychosocial impact extends beyond the affected individuals to their caregivers, who experience elevated levels of stress, anxiety, and depressive symptoms due to the intense demands of caregiving responsibilities (Kayaalp et al. 2021). Caregivers must manage complex medical regimens, advocate for adequate care, balance personal and professional obligations, and face substantial financial burdens associated with medical treatments, adaptive equipment, and specialist consultations (Somanadhan et al. 2025) These pressures often lead to caregiver burnout, which negatively affects family dynamics, caregiving effectiveness, and ultimately, the mental health and wellbeing of children with RDs (Rihm et al. 2022). Families affected by RDs employ diverse coping mechanisms to navigate the significant challenges posed by these conditions, such as seeking emotional support from social networks, engaging in mindfulness practices, and participating in creative or recreational activities to alleviate stress and build resilience (Walkowiak et al. 2024; Kenny et al. 2022). Caregivers often actively educate themselves about their child’s condition, treatments, and resources, typically using online support groups and patient advocacy organisations (Szlamka et al. 2022). However, such coping strategies alone often prove insufficient without systemic support. Structured interventions, including family-centred counselling, psychosocial education, and resilience-building workshops, significantly enhance coping effectiveness (Anderson et al. 2013). Effective resilience involves a combination of individual traits such as optimism and emotional regulation, strong family cohesion, effective communication, and systemic support like accessible healthcare, financial assistance, and educational accommodations (Schafer 2022; Nevin et al. 2023) Innovative interventions such as art therapy and mindfulness-based stress reduction have also shown promise in fostering resilience and emotional well-being (Buckle et al. 2024). Furthermore, effective communication between healthcare providers and families is essential yet frequently inadequate. Parents often report feeling unheard or insufficiently informed during clinical interactions, increasing stress and mistrust in healthcare systems (Witt et al. 2023; Navein et al. 2022). Fragmented care involving multiple specialists frequently results in inconsistent or contradictory information, complicating coordination and treatment management (Joo 2023). To address these issues, interdisciplinary, family-centred care models that integrate medical, emotional, and social support have proven effective. These holistic approaches enhance communication, foster caregiver involvement in decision-making, improve coping strategies, and significantly increase satisfaction with care, thereby addressing the comprehensive psychosocial needs of RD families (Kuo et al. 2011; Witt et al. 2023; Carrington et al. 2021; Cassidy et al. 2023). This systematic review critically evaluates the psychosocial and mental health challenges experienced by children and adolescents with RDs and their primary caregivers. Specifically, it explores the daily emotional distress and practical challenges faced by affected young individuals, examines the psychological impacts and caregiving burdens experienced by their primary caregivers, identifies coping mechanisms and resilience strategies adopted by families, and evaluates systemic gaps in existing care frameworks. Ultimately, this review proposes integrated, family-centred care approaches aimed at improving quality of life and mental health outcomes for families dealing with RDs. Materials and Methods This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines (Page et al. 2021) to ensure transparency and rigour. The PICOS framework (Population, Interventions, Comparators, Outcomes, and Study Designs) was used to define the eligibility criteria for the studies included in this review. Search Strategy Two researchers (GM and DVF) independently searched for quantitative and qualitative studies reporting the mental health challenges, psychosocial impact, caregiver burden, coping mechanisms, and resilience strategies of children and adolescents with RDs (ages 3-17 years). The search for relevant studies was conducted in October 2024 across several electronic databases: PubMed, PsycINFO and Google Scholar. Boolean operators (AND, OR) were used to combine keywords. The search strategy was: (“rare diseases” OR “genetic disorders” OR “chronic illness” OR “inherited diseases” OR “metabolic disorders”) AND (“children” OR “adolescents” OR “youth” OR “minors” OR “young people”) AND (“mental health” OR “psychological distress” OR “anxiety” OR “depression” OR “emotional distress” OR “behavioural issues” OR “peer relationships”) AND (“caregiver burden” OR “family stress” OR “caregiver experiences” OR “parental perspective”) AND (“coping strategies” OR “resilience” OR “psychosocial interventions” OR “stress management”). Articles published in the English language were included. Studies included in this review were selected based on their alignment with the PICOS criteria, focusing on the experiences of children with rare diseases, their caregivers, and the psychosocial challenges they face. No temporal restrictions were applied to the search. References from the selected articles were inspected for potential additional studies. Any disagreements between the two assessors were resolved by consensual agreement. Eligibility Criteria Articles were selected based on clearly defined eligibility criteria, which included the target population (participants), the methodological approaches or interventions applied, the comparative elements between studies, the outcomes evaluated, and the study designs, all of which are detailed in the PICOS framework outlined in Table 1. This systematic review explored interventions which were directly linked to the mental health challenges and psycho-social impact of children and adolescents, and their caregivers, with RDs comprising of family-focused interventions (including the complex interaction between the family and healthcare systems), psycho-educational interventions (including the impact of effective coping mechanisms and empathic communication), interdisciplinary care, psychosocial interventions (including social support and financial support), and surgical/medical treatment for RDs (such as surgical reconstruction of oesophageal atresia). The assessed outcome was the mental health and psycho-social impact of RDs in children/adolescents and their caregivers, including mental health symptoms, emotional distress, resilience strategies, caregiver stress, social integration, and quality of life. Table 1 PICOS Framework PICOS Description Population - Children and adolescents (3–17 years) with RDs - Caregivers of children with RDs Intervention - Family-focused interventions - Psycho-educational interventions - Interdisciplinary care - Psycho-social interventions - Surgical and medical treatment for RDs Comparator - Children without RDs and their caregivers Outcome - Mental health and psycho-social impact of RDs in children/adolescents and their caregivers) Study Design Inclusive of all study designs due to lack of research on the topic. Study Selection and Data Extraction Duplicates identified during the search process were manually removed. Following this, the titles and abstracts of the remaining articles were independently reviewed by the two researchers (GM and DVF) to assess their relevance according to the predefined PICOS criteria. Articles that appeared relevant based on the title and abstract screening were then assessed in full by the same researchers. In cases where there was uncertainty regarding the potential inclusion of an article, the main researcher (GM) discussed with the second researcher (DVF), a consultant psychiatrist working in Child and Adolescent Mental Health Services in Malta, to establish a consensus. Studies that were deemed irrelevant, such as editorials and special editions were excluded from further review. Additionally, articles published in languages other than English were not considered for the final stage of analysis. Quality Assessment and Risk of Bias The Mixed Methods Appraisal Tool (MMAT; (Hong et al. 2018) was used to assess the quality of the chosen manuscripts (Table 2). This tool was chosen as it is validated to assess both qualitative and quantitative methods included in the review. The MMAT is made of the following components: S1: Are there clear research questions? S2: Do the collected data allow to address the research questions? 1.1: Is the qualitative approach appropriate to answer the research question? 1.2: Are the qualitative data collection methods adequate to address the research question? 1.3: Are the findings adequately derived from the data? 1.4: Is the interpretation of results sufficiently substantiated by data? 1.5: Is there coherence between qualitative data sources, collection, analysis and interpretation? 5.1. Is there an adequate rationale for using a mixed methods design to address the research question? 5.2. Are the different components of the study effectively integrated to answer the research question? 5.3. Are the outputs of the integration of qualitative and quantitative components adequately interpreted? 5.4. Are divergences and inconsistencies between quantitative and qualitative results adequately addressed? 5.5. Do the different components of the study adhere to the quality criteria of each tradition of the methods involved? Results Study Selection Following screening, six studies were included from a total of 2156 studies (Figure 1); these related to the psychosocial and mental health challenges of children and adolescents with RDs and their caregivers. Figure 1 Prisma Flow Diagram (Page M. J et al 2021) Study Characteristics The included studies (carried out in five countries) highlighted emotional, social, systemic, and financial burdens, as well as coping and communication needs. Most were qualitative with small sample sizes, consistent with qualitative research principles, while one used a quantitatively driven mixed-methods design (Braun and Clarke 2006). Figure 2 Summary of the Key Findings of Each Study, Including the Main Author, Demographics, Year of Publication, Study Type, Tools Used, and the Rare Diseases Addressed. Author (Year) Country Type Participants Sampling method Tools Rare Diseases Quality Assessment (Siddiq et al. 2016) Canada Qualitative Parents / Caregivers (n = 21) Purposive Semi-structured interviews Inherited metabolic diseases 5 (Pierre-Louis et al. 2017) USA Qualitative Parents (n = 30) Purposive Focus Groups Neurofibromatosis type 1 and type 2 5 (Dellenmark-Blom et al. 2023) Sweden Mixed-Method Prognosis study, Level II Families (n = 26) No sampling: full cohort recruited Strengths & Difficulties Questionnaire (SDQ); Generic Health Related Quality of Life (PedsQL 4.0); Condition Specific Health related Quality of Life (EA-QOL) Long-Gap Oesophageal atresia 5 (Buckle et al. 2024) Ireland Qualitative Children and Young People (n = 11) Purposive Semi-structured interviews Phenylketonuria, Gaucher Disease, dystonia, homocystinuria, haemolytic uremic syndrome, cystinosis, kidney transplant (unknown diagnosis) 5 (Smits et al. 2022) Netherlands Qualitative Parents (n = 12) Purposive Semi-structured interviews Genetic or complex condition 5 (Buckle et al. 2024) Ireland Qualitative Children (n = 7) Purposive Single art session facilitated by an art therapist, followed by semi-structured interviews Craniofacial condition, Gaucher, dystonia, phenylketonuria, homocystinuria 5 These studies reviewed offer complementary yet diverse perspective on the psychosocial impact of RDs. Two studies (Siddiq et al. 2016; Smits et al. 2022) underscored the emotional toll on caregivers, highlighting advocacy roles and the strain of navigating complex healthcare systems. Siddiq et al. focused specifically on inherited metabolic disorders, whereas Smits et al. examined a wider spectrum of genetic and complex conditions, stressing the importance of interdisciplinary care and empathic communication (Pierre-Louis et al. 2017) explored parental experiences in neurofibromatosis, identifying compounded stress from stigma and body symptomatology. Dellenmark-Blom et al. (2023) employed a mixed-methods approach, combining validated quantitative tools (SDQ, PedsQL 4.0) with qualitative results to generate robust evidence on the psychosocial consequences of long-gap oesophageal atresia. Buckle et al. (2024) synthesised children’s perspectives across two studies, showing how social exclusion and creative outlets such as art therapy shape emotional expression, resilience, and identity. In tandem, these studies reveal overlapping themes of emotional distress, caregiver burden, and systemic gaps in support, while their methodological and population-specific variations enrich the understanding of RD experiences. Emotional Distress and Mental Health Challenges Children and adolescents with RDs faced heightened emotional distress compared to their peers, driven by the chronic, unpredictable, and often debilitating nature of their conditions. Across all studies, common themes included anxiety, depression, social isolation, and low self-esteem, underscoring the broad psychosocial impact of RDs. Dellenmark-Blom et al. (2023) reported that 46% of with long-gap oesophageal atresia (LGEA) experienced significant mental health difficulties, including hyperactivity, inattention, and challenges forming peer relationships, all of which reduced health-related quality of life (HRQoL). Physical comorbidities, such as asthma and sleep disturbances, further compounded psychological struggles. Social exclusion was consistently described, with children excluded from sports, school events, and peer activities due to physical limitations, frequent hospitalisations, or lack of understanding from peers and educators (Buckle et al. 2024). The tension between wanting to “fit in” while “feeling different” created significant emotional strain, fuelling anxiety and diminished self-worth. Stigma, particularly for those with visible symptoms or medical equipment, intensified these difficulties, leading to bullying, shame, and barriers to forming meaningful relationships (Pierre-Louis et al. 2017; Buckle et al. 2024). Adolescents were identified as particularly vulnerable, struggling to balance the dual demands of managing their condition while striving for independence and social integration (Buckle et al. 2024). Gender-based differences were also noted, with boys showing higher rates of emotional and social difficulties (Dellenmark-Blom et al. 2023). Academic challenges further compounded these pressures, as repeated absences disrupted learning and peer connections, perpetuating cycles of underachievement and isolation (Siddiq et al. 2016). While these findings revealed significant psychological vulnerabilities, several reviewed studies also emphasised the lack of specialised mental health resources tailored to the needs of children with RDs (Smits et al . 2022; Pierre-Louis et al . 2017). The absence of early psychosocial interventions left many children without adequate support, highlighting a critical gap in care. Caregiver Insights and Stress Caregivers of children with RDs face profound physical, emotional, and financial burdens that shape their well-being and caregiving capacity. Across all included studies, caregiving was described as an all-encompassing role requiring constant advocacy, care coordination, and management of complex medical needs, often at the expense of caregivers’ health, careers, and social lives. Pierre-Louis et al. (2017) documented the heightened stress levels experienced by parents of children with neurofibromatosis, emphasising the emotional toll of stigma linked to visible symptoms. Caregivers reported isolation, helplessness, and fatigue, noting that their distress directly affected their ability to provide consistent care and influenced broader family dynamics. Smits et al. (2022) highlighted similar challenges, including navigating fragmented healthcare systems, coping with uncertainty, and balancing caregiving with work and family responsibilities. Caregivers expressed frustration at the lack of interdisciplinary support and empathic communication, identifying the need for family-focused models of care that address both medical and psychosocial needs. Siddiq et al. (2016) explored the distinctive challenges of caring for children with inherited metabolic diseases, where parents not only managed strict dietary and treatment regimens but also ffound themsleves requently educated healthcare professionals unfamiliar with their child’s condition. This parental sense of advocacy extended to ensuring that their children received appropriate accommodations in educational and social settings, further straining caregivers’ mental and emotional resources Financial pressures were reported across all studies, including costs for treatments, travel, adaptive equipment, and lost income due to caregiving demands. Smits et al. (2022) and Siddiq et al. (2016) highlighted how financial strain compounded emotional distress and restricted access to support services. Caregivers also prioritised their child’s needs over their own, leading to strained family relationships (Pierre-Louis et al. 2017; Smits et al. 2022). The absence of structured support systems often meant that caregivers bore the brunt of these challenges alone, further deepening their sense of fatigue and emotional exhaustion. Coping Mechanisms and Resilience Strategies Despite the abovementioned challenges, families demonstrated remarkable resilience, employing various coping strategies to navigate their circumstances. Siddiq et al. (2016) reported that caregivers frequently engaged in proactive information-seeking behaviours, turning to online resources, support groups, and advocacy organisations. These efforts fostered empowerment and emotional resilience, while planning and problem-solving strategies helped caregivers maintain a sense of control in managing uncertainty. For children, creative outlets such as art therapy provided powerful means of coping. Buckle et al. (2024) highlighted the therapeutic value of artistic expression, which not only facilitated emotional processing but also enabled children to articulate their experiences and strengthen identity formation. Such activities often enhanced communication within families, promoting stronger emotional bonds. Structured interventions, including family-centred counselling and resilience training, were also shown to equip families with practical tools to manage stress, improve communication, and enhance psychological flexibility (Buckle et al. 2024). Social support networks emerged as another protective factor. Smits et al. (2022) emphasised the importance of connections with other parents through formal groups or informal community networks, which provided practical advice, validation, and solidarity. Similarly, Pierre-Louis et al. (2017) noted the potential of resilience-based interventions, particularly when delivered in accessible formats tailored to family needs. Collectively, these studies underline that while individual coping strategies and peer networks are essential, they remain insufficient in isolation. Sustained resilience requires systemic support through integrated care models that combine medical, psychological, and social interventions to address the multifaceted challenges of RD families. Communication and Support Needs Effective communication between healthcare providers and families emerged as a critical theme across all studies. Caregivers frequently reported feeling unheard or dismissed in clinical encounters, which exacerbated stress and hindered their ability to advocate for their children (Pierre-Louis et al. 2017; Smits et al. 2022). These difficulties were often compounded by fragmented care systems requiring families to coordinate across multiple providers. Both studies emphasised the importance of clear, empathic, and transparent communication to build trust and improve care satisfaction. Siddiq et al. (2016) further highlighted caregiver dissatisfaction with non-specialist providers unfamiliar with the complexities of RDs. This lack of expertise contributed to delays and inconsistent care, intensifying emotional and logistical burdens. Siddiq et al . (2016) underscored the need for enhanced training in RD management, particularly in general healthcare settings where caregivers often encounter the greatest frustrations. Interdisciplinary care models were consistently identified as best practice for bridging communication gaps. Smits et al. (2022) and Pierre-Louis et al. (2017) both highlighted the value of integrated models that combine medical, psychological, and social support. Such approaches ensure consistent messaging, streamline care delivery, and reduce the strain of navigating fragmented systems. interdisciplinary care teams that include geneticists, psychologists, social workers, and educators, were shown to foster a more holistic approach to care, addressing both the medical and psychosocial dimensions of RD management. Educational contexts also shaped communication experiences. Buckle et al. (2024) identified significant gaps in awareness among educators and peers, which contributed to inadequate accommodations and social exclusion for children with RDs. Parents often assumed the role of mediators, explaining their child’s condition to secure basic support. Tailored educational programs, peer-awareness initiatives, and teacher training were highlighted as essential for reducing stigma and fostering inclusivity, helping children feel recognised and valued within their school communities. Beyond clinical and educational contexts, communication was also linked to access to reliable information. Smits et al. (2022) stressed the importance of providing families with access to reliable information about their child’s condition, treatment options, and available resources. The integration of digital tools, such as telehealth platforms and online educational materials, were identified as a promising avenue for enhancing communication and providing families with the information they need to navigate complex care systems. Pierre-Louis et al. (2017) further suggested that resilience-based interventions delivered via live video formats could help bridge geographical and logistical gaps, making support services more accessible to a wider range of families. Synthesis of Key Findings The results from the individual studies were synthesised by juxtaposing results in a table (Table 2) and being reviewed independently by two researchers (GF and DVF) until a consensus was reached. Due to the highly qualitative nature of the included studies, meta-analysis or other types of quantitative syntheses were not possible. Table 2 Synthesises the Key Findings from the Studies, Highlighting the Overarching Themes and Insights Gained from the Analysis. Study Synthesis of Key Findings (Siddiq et al. 2016) “New normal”: Adapting to the daily complexities of parents/caregivers managing their children's conditions. These findings highlight the need for improved coordination of care and support systems to address both the social and healthcare needs of families navigating the complexities of IMD management. (Pierre-Louis et al. 2017) Parents experienced significant emotional and physical health challenges due to the demands of caregiving, with existing interventions for parents of children with chronic illnesses proving ineffective in alleviating such burdens. Findings emphasised the need for accessible delivery methods like live video formats to enhance participation and support among geographically dispersed families. (Dellenmark-Blom et al. 2023) This study indicates that nearly half (46%) of children with LGEA experience mental health challenges, as reported by parents. Common concerns include difficulties in forming peer relationships and symptoms related to hyperactivity and inattention. Boys appeared to be more vulnerable, with contributing factors such as asthma and sleep issues playing a significant role. These mental health challenges were associated with a decline in health-related quality of life, underscoring the need for comprehensive follow-up care. (Buckle et al. 2024) Identified two primary themes related to the lived experiences of children with RDs: Knowledge and understanding of their conditions and the tension between “fitting in” versus “feeling different”. Overall, while hospital experiences were often viewed positively, social life was significantly impacted, highlighting a need for greater awareness and support in school settings to foster inclusivity and understanding among peers. (Smits et al. 2022) The study investigated the common needs of parents caring for children with RDs, identifying eight primary themes: Family-focused care, coping with uncertainty, empathic communication, practical support, information, psychological support, interdisciplinary care, and social support. Findings highlight the necessity for a holistic, interdisciplinary approach in paediatric care, addressing both the medical and psychosocial needs of families. (Buckle et al. 2024) This study elucidated that children with RDs encounter significant psychosocial challenges, including feelings of isolation and concerns regarding their identity. These aspects are notably influenced by the presence of supportive relationships with peers and family members. Furthermore, the findings underscore the necessity for holistic and child-centred research approaches (e.g., art) that honour and actively engage children as experts in their own lived experiences. Risk of Bias Two researchers (GF and DVF) independently reviewed the included studies, ensuring that each study met the inclusion criteria. After evaluating the methodological rigour and addressing potential biases, it was determined that all six studies fit the established criteria, and none were excluded from the analysis. The MMAT provided a comprehensive framework for evaluating the quality of the studies, and all studies were considered to have met the required standards for inclusion in the review. Table 1 Mixed Method Appraisal Tool (MMAT) Assessment of Study Quality (“Y” = 1; “N” = 0) First Author, Publication Date All Studies Qualitative studies Mixed Methods S1 S2 1.1 1.2 1.3 1.4 1.5 2.1 – 4.5 5.1 5.2 5.3 5.4 5.5 Siddiq (2016) Y Y Y Y Y Y Y / / / / / Pierre-Louis (2017) Y Y Y Y Y Y Y / / / / / Dellenmark-Blom (2023) Y Y / / / / / Y Y Y Y Y Buckle (2024) Y Y Y Y Y Y Y / / / / / Smits (2022) Y Y Y Y Y Y Y / / / / / Buckle (2024) Art Method Y Y Y Y Y Y Y / / / / / Y Yes, N No, C Can't determine Discussion This systematic review provides a detailed examination of the psychosocial and mental health challenges encountered by children and adolescents with RDs and their caregivers. The findings reveal recurring themes, including emotional distress, caregiver burden, coping strategies, and the significance of effective communication. These insights not only reinforce but also expand upon existing literature, presenting a nuanced understanding of the multifaceted challenges faced by RD families. By comparing the reviewed studies with prior research, this discussion elucidates consistencies, discrepancies, and evolving perspectives in the field. This systematic review revealed that children and adolescents with RDs endure heightened levels of anxiety, depression, and social isolation. These psychological challenges are often attributed to the chronic and debilitating nature of their conditions, which impose frequent hospitalisations, physical limitations, and barriers to participating in typical childhood activities. Furthermore, it also indicated that these children and adolescents with RDs experience a potentially complex symptomatology associated with hyperactivity, social development, identity formation, struggles in forming peer relationships, the desire to “fit in” and the experience of “feeling different” (Buckle et al. 2024; Dellenmark-Blom et al . 2023). These observations align with earlier findings (Uhlenbusch et al. 2019 which emphasise the prevalence of psychological distress in RD populations, and the relationship between stigmatisation and its detrimental impact on self-esteem. However, in addition to existing literature, this systematic review highlights the distinct ways in which these challenges manifest across different contexts. This study further emphasised the impact of RDs on caregivers, who shoulder immense emotional, physical, and financial burdens, and taking on an invaluable advocacy role especially when navigating within non-specialised healthcare systems with already overstretched budgets. This further necessitates efficient access to psychological support, family-focused care, and empathic communication from healthcare providers, highlighting the importance of peer support networks for caregivers to prevent social isolation (Smits et al. 2022; Siddiq et al. 2016). These findings corroborate earlier research by Dellve et al. (2006) which underscored the significant stress and fatigue experienced by caregivers. Furthermore, previous research has also highlighted the financial strain of managing medical expenses and specialised treatments (Anderson et al. 2013) During the systematic process of reviewing included studies, the authors identified a consistent pattern of helplessness experiences by caregivers. However, Chung et al. (2022) reported that RDs are an emerging public health priority. This contrasts with the findings elucidated from our results, which might imply a lack of specific resources for specialised services working with RD patients. This might inform the development of innovative services for RD families given the potential stigma associated with RDs (Baynam et al. 2024). As outlined in this systematic review, providing temporary relief, and fostering resilience is imperative for caregivers of children and adolescents with RDs, and emphasised the importance of proactive information-seeking behaviours and advocacy (Buckle et al. 2024; Siddiq et al. 2016). This aligned with previous findings in the literature describing coping strategies as integral to how families navigate the challenges associated with RDs, and the importance of emotional support from social networks, creative outlets, family-centred counselling, resilience training, and mindfulness practices to manage stress (Dellve et al. 2006; Anderson et al. 2013). In keeping with the notion of caregiver support, research has also emphasised the benefits of online communities to reduce isolation and foster a sense of belonging (Ashtari and Taylor, 2022). This systematic review, in conjunction with previous research, delineates how integrating the aforementioned approaches may allow healthcare systems to better address the holistic needs of RD families. It is understandable that RDs may pose as a potentially traumatic factor in one’s life (Zhang 2023). Previous research has also identified that such traumatic factors may foster an emotional connection between loved ones (Raz et al. 2024). Therefore, this may serve as a protective factor for RD families, notwithstanding the need for further resources to avoid parental burnout and excessive burden of care. Communication has been highlighted as a crucial theme especially between healthcare providers and families, which serves to minimise caregiver burnout and bilaterally ameliorate the professional-caregiver alliance (Smits et al. 2022; Pierre-Louis et al. 2017). Inconsistencies in information provision and a lack of transparency were also reported as perpetuating the subjective dissatisfaction among caregivers, especially towards non-specialised healthcare services (Siddiq et al. 2016). This mirrors previous reports describing the limitations associated with fragmented care pathways, and the importance to develop the necessary frameworks for integrating medical, emotional, and social support, thereby improving care coordination and outcomes (Richardson et al. 2024). The frequently encounter stigma by children and adolescents in educational and social settings has been heavily implicated in this systematic review, including the importance of fostering inclusivity within schools to mitigate these challenges. This further highlighted the central role of stigma in shaping the psychosocial experiences of RD patients and caregivers (Buckle et al. 2024). These findings align with previous research identifying a lack of understanding among educators as a key barrier to social integration (García-Perales et al. 2022) and the importance of utilising systematic efforts (and not solely individual interventions) to promote awareness and inclusivity (Belzer et al. 2022). Furthermore, Currie and Szabo (2018) documented the academic and social disruptions caused by frequent absences and limited support in schools. A gradual transition towards a holistic educational environment has been frequently reported (Sankar, 2025). However, from the results generated in this systematic review, this does not seem to be the case for students with RDs. The lack of educational institutions supporting children and adolescents with RDs has been frequently mentioned, with an emphasis on the lack of tailored support systems within schools, contributing to feelings of exclusion and academic underachievement (Buckle et al. 2024). School environments can act as a microcosm of societal attitudes toward individuals with RDs, and the findings in this review here reaffirm that perspective. Efforts to train educators in understanding the unique challenges faced by RD patients, coupled with peer-awareness programs, can foster a more inclusive environment that enhances both educational and social outcomes (Röjvik et al. 2023). Financial strain in RD families was also a recurring theme in this review, particularly for caregivers tasked with managing costly medical treatments and adaptive equipment (Siddiq et al. 2016). Domaradzki et al. (2025) has also reported such financial challenges associated with RD care, which not only exacerbate emotional stress but also impact the caregivers’ ability to provide consistent and effective support. This underscores the need for policy interventions that address these economic disparities, including subsidies for medical expenses and expanded access to respite care, which may help alleviate caregiver strain and improve the struggling family dynamic (Somanadhan et al. 2025) All the studies included in this systematic review highlighted the importance of addressing disparities in access to care. While previous research (Forman et al. 2012) had acknowledged gaps in RD healthcare services, this systematic review further explores how these disparities manifest in day-to-day challenges for families, highlighting the fragmentation of healthcare systems secondary to the lack of coordinated care and specialised pathways (Smits et al. 2022). Healthcare models supporting integration of care are crucial in such situations (Taruscio et al. 2015). One study in this systematic review (Pierre-Louis et al. 2017) greatly focused on how telemedicine and digital platforms could help bridge gaps in the access of care, particularly for geographically isolated families. This underscores the potential for innovative technologies to address long-standing barriers in RD management. Overall, there was a consensual agreement in this systematic review that the psychosocial difficulties of caregivers accentuate the urgent need for mental health interventions tailored to their needs. This might mitigate the physical and logistical challenges, including emotional turbulence, that families experience by introducing more logistically friendly digital measures of healthcare. To the authors’ knowledge, this represents the first systematic review to specifically examine the psychosocial impact and mental health challenges of RDs families, including the need for a paradigm shift in the way healthcare systems, educational institutions, and social policies address the challenges faced by these families. The review highlights the critical role of interdisciplinary and family-centred care in bridging the gaps between medical, psychological, and social support services. It also emphasises that systemic barriers, such as fragmented healthcare delivery, inadequate educational support, and financial strain, not only exacerbate the emotional and psychological burdens of RD families but also hinder their overall quality of life. The resilience displayed by RD families presents valuable insights into strategies that work, such as peer support, creative therapies, and advocacy. However, the current reliance on individual coping mechanisms reflects the absence of robust systematic frameworks. These findings should serve as a call to action for healthcare providers, educators, and policymakers to prioritise equitable access to comprehensive, coordinated care models that address the multifaceted needs of RD families. This systematic review contributes to the growing recognition that addressing the psychosocial dimensions of RDs is not only a healthcare challenge but also a critical step toward achieving broader social justice and inclusion. Limitations Despite the insights provided by this systematic review, several limitations must be acknowledged. Only six studies met the inclusion criteria, reflecting the scarcity of research on the psychosocial experiences of RD families. While this highlights the importance of the review in addressing a gap in the literature, the small number of studies limits the generalisability of the findings. As most included studies were qualitative, the review followed an interpretivist epistemological paradigm. Although this reduces generalisability, it allowed for a deeper exploration of lived experiences. The inclusion of one mixed-methods study introduced a post-positivist perspective, partially enhancing generalisability and compensating for methodological limitations. The predominance of qualitative approaches is appropriate given the complexity of psychosocial experiences. However, the absence of longitudinal studies limits understanding of how emotional distress and coping strategies evolve over time and restricts causal inference. Despite these limitations, this review offers important strengths. It synthesises evidence that provides meaningful insights into the psychosocial burden experienced by children with RDs and their caregivers, emphasising the need for improved support systems. Key themes, including emotional distress, caregiver burden, and communication challenges, were identified, offering a foundation to inform future research, interventions, and policy development. Future Implications Healthcare systems must prioritise the development of integrated, family-centred care models that provide medical, psychological, and social support within a unified framework. Telehealth and digital tools should be utilised to enhance accessibility, particularly for families in remote or underserved areas, and to improve communication and care coordination across healthcare teams. Subsidies for medical treatments, adaptive equipment, and travel for specialist care can significantly reduce the financial burden on families. Expanding insurance coverage and increasing access to respite care programmes for caregivers are further measures that may mitigate stress and improve overall well-being. Policymakers should also advocate for increased funding for RD research and caregiver support programmes, recognising the long-term benefits of these investments for families and healthcare systems. Resilience-building interventions are essential to enhance the emotional and psychological well-being of families affected by RDs. Expanding access to family counselling, peer support networks, and mindfulness-based interventions may help caregivers and children manage stress and strengthen coping mechanisms. Non-traditional therapeutic approaches, such as art therapy, offer valuable opportunities for emotional expression and can support family relationships. Digital platforms may also be leveraged to provide online peer support and educational resources, fostering community connection and empowerment. Training healthcare professionals is imperative to improve understanding of the unique challenges associated with RDs and to promote empathetic communication, thereby strengthening trust and caregiver experiences. Educational systems also play a critical role in supporting children and adolescents with RDs. Tailored training programmes for educators are recommended to address individual needs and ensure appropriate accommodations that support academic progress and social integration. Peer-awareness initiatives and anti-stigma programmes within schools are equally important in fostering inclusive environments and reducing isolation. Public education campaigns and community-based initiatives can extend these efforts to address societal stigma. Conclusion This systematic review highlights the substantial psychosocial and mental health challenges experienced by RD families, underscoring the urgent need for targeted interventions across research, clinical practice, and policy. Children with RDs face significant emotional distress, including anxiety and depression, driven by physical limitations, frequent hospitalisations, stigma, and social exclusion. Adolescents appear particularly vulnerable as these challenges intersect with identity formation and social integration, resulting in reduced quality of life. Caregivers experience multifaceted burdens, including emotional exhaustion, financial strain, and disruption to personal and professional lives. Many adopt advocacy roles to navigate fragmented healthcare systems, increasing stress and burnout, while the rarity of conditions often leads to social isolation and limited peer support. Despite these challenges, families demonstrate notable resilience through proactive coping strategies such as information-seeking, mindfulness, peer support, and creative interventions like art therapy. However, these strategies remain insufficient without robust systemic support. The findings reveal critical gaps in healthcare communication, interdisciplinary coordination, educational accommodations, and financial support. By synthesising limited but meaningful evidence, this review contributes to an under-researched field and provides a foundation for future research and service development. Further longitudinal and quantitative studies are needed to better understand evolving psychosocial needs and to inform equitable, inclusive interventions for RD families. Abbreviations Rare Disease RD Quality of Life QOL Health Related Quality of Life HQoL Strengths and Difficulties Questionnaire SDQ Generic Health Related Quality of Life PedsQL 4.0 Condition Specific Health related Quality of Life Long gap oesophageal atresia EA-QOL LGEA Declarations Consent to Participate Declaration Consent was not required due to nature of this study Ethics Approval declaration Ethics Approval by Learna/University of South Wales Funding Declaration None Human Ethics and Consent to Participate Not Applicable due to nature of this study Statements and Declarations No competing interests Acknowledgments University of South Wales Author Contribution GF- Main ResearcherDVF- Second ResearcherKN- Supervisor References Kole A, Faurisson F. (2009). The voice of 12,000 patients: Experiences and expectations of rare disease patients on diagnosis and care in Europe: A report based on the EurordisCare3 surveys. 2009; (C. Nourissier, Ed.). Paris: Eurordis. Page, M. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9253757","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":623136029,"identity":"a61dc5dd-94be-4b97-b19a-d41ba180548c","order_by":0,"name":"Gertrude Fenech","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYPACZiBmbGBgKLBgYG9vIKgcpBSmxUCCgefMAbCwBBFaQACk5UYCfi3y7r3PH1e2WcsxiB1u/PDDQEKOR/L5xcc8DNvqcGkxPHPcsPFsW7oxg3Ris2SPgYQxj3ROsTEPw22cthjOSGNsbGw7nNggndjGwGMgkbhfOidNcgY+LfOfgbXUg7Qw/jGQqO+RPINfi7wEG1hLAtBhbcxAWxJ4JNiPSXzAo8WAJ41xZsO5dMM2oF+kZQwkDHt4cpgNPhjclmzAZUv7MYaPDWXW8vzS6Q8/vqmwkedhP/7wQULFbX6cthyAMtgQYjwGQHFcGoC2YLGe/QFu9aNgFIyCUTASAQCzP1BAAuohUAAAAABJRU5ErkJggg==","orcid":"","institution":"University of Malta","correspondingAuthor":true,"prefix":"","firstName":"Gertrude","middleName":"","lastName":"Fenech","suffix":""},{"id":623136030,"identity":"8828d339-8cf4-4bd7-b160-c0a19acf12fe","order_by":1,"name":"Daniel Vella Fondacaro","email":"","orcid":"","institution":"University of Malta","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"Vella","lastName":"Fondacaro","suffix":""},{"id":623136031,"identity":"323b99bd-824b-4217-b129-9f862a85e187","order_by":2,"name":"Karl J. New","email":"","orcid":"","institution":"University of South Wales","correspondingAuthor":false,"prefix":"","firstName":"Karl","middleName":"J.","lastName":"New","suffix":""}],"badges":[],"createdAt":"2026-03-28 15:09:35","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9253757/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9253757/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107243556,"identity":"93fa1a5b-f82c-4ca3-bdae-ebf3ad892262","added_by":"auto","created_at":"2026-04-19 07:52:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":599258,"visible":true,"origin":"","legend":"\u003cp\u003ePrisma Flow Diagram (Page M. J et al 2021)\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9253757/v1/b35f7ac7dabf4c3e3135e4c5.png"},{"id":107482531,"identity":"136a937c-35e4-4e09-885c-b6d8a48e6d7b","added_by":"auto","created_at":"2026-04-22 02:23:54","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":226380,"visible":true,"origin":"","legend":"\u003cp\u003eSummary of the Key Findings of Each Study, Including the Main Author, Demographics, Year of Publication, Study Type, Tools Used, and the Rare Diseases Addressed.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9253757/v1/99c46ad989ae879f1975dcdc.jpg"},{"id":107704945,"identity":"c41cab59-791c-4da8-b774-bde5060bdcf3","added_by":"auto","created_at":"2026-04-24 09:04:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1070893,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9253757/v1/43ce27c7-f1a9-4b48-ae36-c6f8136b2702.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mental Health Challenges and Psychosocial Impact of Rare Diseases in Children and Adolescents -A Systematic Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRare Diseases (RDs) are defined differently globally; in the European Union, a disease is considered rare if it affects fewer than 1 in 2,000 individuals, whereas in the United States, one RD affects fewer than 200,000 people nationwide Kole and Faurisson (2009).\u0026nbsp;Collectively, RDs impact an estimated 300 million individuals worldwide, spanning over 6,000 distinct conditions that encompass genetic, infectious, degenerative, and proliferative disorders (Nguengang Wakap et al. 2019). Approximately 80% of RDs are genetic, and roughly 70% manifest in early childhood, requiring lifelong, multidisciplinary care (European Commission, 2024). The heterogeneous nature and rarity of these conditions frequently result in limited awareness among healthcare providers, leading to prolonged diagnostic delays, often described as the \"diagnostic odyssey\" (Witt et al. 2023). Such delays significantly impact patients and families emotionally, often involving consultations with multiple specialists before receiving accurate diagnoses (Ferreira 2019).\u003c/p\u003e\n\u003cp\u003eChildren and adolescents with RDs commonly experience significant mental health symptoms and psychosocial challenges, including anxiety and depressive symptoms, which are closely linked to chronic physical symptoms, frequent hospitalisations, and physical restrictions imposed by their conditions (Belzer et al. 2022). These physical limitations combined with social stigma, intensify feelings of isolation, negatively impacting self-esteem and increasing social withdrawal (Nevin et al. 2023). This psychological burden is compounded by the limited availability of specialised mental health services, despite evidence that early psychosocial interventions significantly improve mental health outcomes (Richardson et al. 2024).\u003c/p\u003e\n\u003cp\u003eThe profound psychosocial impact extends beyond the affected individuals to their caregivers, who experience elevated levels of stress, anxiety, and depressive symptoms due to the intense demands of caregiving responsibilities (Kayaalp et al. 2021). Caregivers must manage complex medical regimens, advocate for adequate care, balance personal and professional obligations, and face substantial financial burdens associated with medical treatments, adaptive equipment, and specialist consultations (Somanadhan et al. 2025) These pressures often lead to caregiver burnout, which negatively affects family dynamics, caregiving effectiveness, and ultimately, the mental health and wellbeing of children with RDs (Rihm et al. 2022).\u003c/p\u003e\n\u003cp\u003eFamilies affected by RDs employ diverse coping mechanisms to navigate the significant challenges posed by these conditions, such as seeking emotional support from social networks, engaging in mindfulness practices, and participating in creative or recreational activities to alleviate stress and build resilience (Walkowiak et al. 2024; Kenny et al. 2022). Caregivers often actively educate themselves about their child’s condition, treatments, and resources, typically using online support groups and patient advocacy organisations (Szlamka et al. \u0026nbsp;2022). However, such coping strategies alone often prove insufficient without systemic support. Structured interventions, including family-centred counselling, psychosocial education, and resilience-building workshops, significantly enhance coping effectiveness (Anderson et al. 2013). Effective resilience involves a combination of individual traits such as optimism and emotional regulation, strong family cohesion, effective communication, and systemic support like accessible healthcare, financial assistance, and educational accommodations (Schafer 2022; Nevin et al. \u0026nbsp;2023) Innovative interventions such as art therapy and mindfulness-based stress reduction have also shown promise in fostering resilience and emotional well-being (Buckle et al. \u0026nbsp;2024).\u003c/p\u003e\n\u003cp\u003eFurthermore, effective communication between healthcare providers and families is essential yet frequently inadequate. Parents often report feeling unheard or insufficiently informed during clinical interactions, increasing stress and mistrust in healthcare systems (Witt et al. \u0026nbsp;2023; Navein et al. \u0026nbsp;2022). Fragmented care involving multiple specialists frequently results in inconsistent or contradictory information, complicating coordination and treatment management (Joo 2023). To address these issues, interdisciplinary, family-centred care models that integrate medical, emotional, and social support have proven effective. These holistic approaches enhance communication, foster caregiver involvement in decision-making, improve coping strategies, and significantly increase satisfaction with care, thereby addressing the comprehensive psychosocial needs of RD families (Kuo et al. \u0026nbsp;2011; Witt et al. 2023; Carrington et al. \u0026nbsp;2021; Cassidy et al. 2023).\u003c/p\u003e\n\u003cp\u003eThis systematic review critically evaluates the psychosocial and mental health challenges experienced by children and adolescents with RDs and their primary caregivers. Specifically, it explores the daily emotional distress and practical challenges faced by affected young individuals, examines the psychological impacts and caregiving burdens experienced by their primary caregivers, identifies coping mechanisms and resilience strategies adopted by families, and evaluates systemic gaps in existing care frameworks. Ultimately, this review proposes integrated, family-centred care approaches aimed at improving quality of life and mental health outcomes for families dealing with RDs.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines (Page et al. 2021) to ensure transparency and rigour. The PICOS framework (Population, Interventions, Comparators, Outcomes, and Study Designs) was used to define the eligibility criteria for the studies included in this review.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eSearch Strategy\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eTwo researchers (GM and DVF) independently searched for quantitative and qualitative studies reporting the mental health challenges, psychosocial impact, caregiver burden, coping mechanisms, and resilience strategies of children and adolescents with RDs (ages 3-17 years). The search for relevant studies was conducted in October 2024 across several electronic databases: PubMed, PsycINFO and Google Scholar. Boolean operators (AND, OR) were used to combine keywords. The search strategy was: (“rare diseases” OR “genetic disorders” OR “chronic illness” OR “inherited diseases” OR “metabolic disorders”) AND (“children” OR “adolescents” OR “youth” OR “minors” OR “young people”) AND (“mental health” OR “psychological distress” OR “anxiety” OR “depression” OR “emotional distress” OR “behavioural issues” OR “peer relationships”) AND (“caregiver burden” OR “family stress” OR “caregiver experiences” OR “parental perspective”) AND (“coping strategies” OR “resilience” OR “psychosocial interventions” OR “stress management”).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eArticles published in the English language were included. Studies included in this review were selected based on their alignment with the PICOS criteria, focusing on the experiences of children with rare diseases, their caregivers, and the psychosocial challenges they face. No temporal restrictions were applied to the search. References from the selected articles were inspected for potential additional studies. Any disagreements between the two assessors were resolved by consensual agreement.\u003c/p\u003e\n\u003ch3 id=\"_Toc187009276\"\u003e\u003cstrong\u003eEligibility Criteria\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eArticles were selected based on clearly defined eligibility criteria, which included the target population (participants), the methodological approaches or interventions applied, the comparative elements between studies, the outcomes evaluated, and the study designs, all of which are detailed in the PICOS framework outlined in Table 1. This systematic review explored interventions which were directly linked to the mental health challenges and psycho-social impact of children and adolescents, and their caregivers, with RDs \u0026nbsp; comprising of family-focused interventions (including the complex interaction between the family and healthcare systems), psycho-educational interventions (including the impact of effective coping mechanisms and empathic communication), interdisciplinary care, psychosocial interventions (including social support and financial support), and surgical/medical treatment for RDs (such as surgical reconstruction of oesophageal atresia). The assessed outcome was the mental health and psycho-social impact of RDs in children/adolescents and their caregivers, including mental health symptoms, emotional distress, resilience strategies, caregiver stress, social integration, and quality of life.\u003c/p\u003e\n\u003cp id=\"_Toc185709627\"\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePICOS Framework\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"600\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ePICOS\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eDescription\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ePopulation\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e- Children and adolescents (3–17 years) with RDs\u003c/p\u003e\n \u003cp\u003e- Caregivers of children with RDs\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eIntervention\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e- Family-focused interventions\u003c/p\u003e\n \u003cp\u003e- Psycho-educational interventions\u003c/p\u003e\n \u003cp\u003e- Interdisciplinary care\u003c/p\u003e\n \u003cp\u003e- Psycho-social interventions\u003c/p\u003e\n \u003cp\u003e- Surgical and medical treatment for RDs\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eComparator\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e- Children without RDs and their caregivers\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eOutcome\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e- Mental health and psycho-social impact of RDs in children/adolescents and their caregivers)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy Design\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eInclusive of all study designs due to lack of research on the topic.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch3 id=\"_Toc187009277\"\u003e\u003cstrong\u003eStudy Selection and Data Extraction\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eDuplicates identified during the search process were manually removed. Following this, the titles and abstracts of the remaining articles were independently reviewed by the two researchers (GM and DVF) to assess their relevance according to the predefined PICOS criteria. Articles that appeared relevant based on the title and abstract screening were then assessed in full by the same researchers.\u003c/p\u003e\n\u003cp\u003eIn cases where there was uncertainty regarding the potential inclusion of an article, the main researcher (GM) discussed with the second researcher (DVF), a consultant psychiatrist working in Child and Adolescent Mental Health Services in Malta, to establish a consensus. Studies that were deemed irrelevant, such as editorials and special editions were excluded from further review. Additionally, articles published in languages other than English were not considered for the final stage of analysis.\u003c/p\u003e\n\u003ch3 id=\"_Toc187009278\"\u003e\u003cstrong\u003eQuality Assessment and Risk of Bias\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe Mixed Methods Appraisal Tool (MMAT; (Hong et al. 2018) was used to assess the quality of the chosen manuscripts (Table 2). This tool was chosen as it is validated to assess both qualitative and quantitative methods included in the review. The MMAT is made of the following components: S1: Are there clear research questions? S2: Do the collected data allow to address the research questions? 1.1: Is the qualitative approach appropriate to answer the research question? 1.2: Are the qualitative data collection methods adequate to address the research question? 1.3: Are the findings adequately derived from the data? 1.4: Is the interpretation of results sufficiently substantiated by data? 1.5: Is there coherence between qualitative data sources, collection, analysis and interpretation? 5.1. Is there an adequate rationale for using a mixed methods design to address the research question? 5.2. Are the different components of the study effectively integrated to answer the research question? 5.3. Are the outputs of the integration of qualitative and quantitative components adequately interpreted? 5.4. Are divergences and inconsistencies between quantitative and qualitative results adequately addressed? 5.5. Do the different components of the study adhere to the quality criteria of each tradition of the methods involved?\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eStudy Selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFollowing screening, six studies were included from a total of 2156 studies (Figure 1); these related to the psychosocial and mental health challenges of children and adolescents with RDs and their caregivers.\u003c/p\u003e\n\u003cp id=\"_Toc185709604\"\u003e\u003cstrong\u003eFigure\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePrisma Flow Diagram (Page M. J et al 2021)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe included studies (carried out in five countries) highlighted emotional, social, systemic, and financial burdens, as well as coping and communication needs. Most were qualitative with small sample sizes, consistent with qualitative research principles, while one used a quantitatively driven mixed-methods design (Braun and Clarke 2006).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSummary of the Key Findings of Each Study, Including the Main Author, Demographics, Year of Publication, Study Type, Tools Used, and the Rare Diseases Addressed.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAuthor (Year)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCountry\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSampling method\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTools\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 207px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRare Diseases\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQuality Assessment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e(Siddiq et al. 2016)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eCanada\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eQualitative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eParents / Caregivers (n = 21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003ePurposive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eSemi-structured interviews\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 207px;\"\u003e\n \u003cp\u003eInherited metabolic diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e(Pierre-Louis et al. 2017)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eQualitative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eParents (n = 30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003ePurposive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eFocus Groups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 207px;\"\u003e\n \u003cp\u003eNeurofibromatosis type 1 and type 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e(Dellenmark-Blom et al. \u0026nbsp;2023)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eSweden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eMixed-Method Prognosis study, Level II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eFamilies (n = 26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eNo sampling: full cohort recruited\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eStrengths \u0026amp; Difficulties Questionnaire (SDQ); Generic Health Related Quality of Life (PedsQL 4.0); Condition Specific Health related Quality of Life (EA-QOL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 207px;\"\u003e\n \u003cp\u003eLong-Gap Oesophageal atresia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e(Buckle et al. 2024)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eIreland\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eQualitative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eChildren and Young People (n = 11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003ePurposive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eSemi-structured interviews\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 207px;\"\u003e\n \u003cp\u003ePhenylketonuria, Gaucher Disease, dystonia, homocystinuria, haemolytic uremic syndrome, cystinosis, kidney transplant (unknown diagnosis)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e(Smits et al. 2022)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eNetherlands\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eQualitative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eParents (n = 12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003ePurposive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eSemi-structured interviews\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 207px;\"\u003e\n \u003cp\u003eGenetic or complex condition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e(Buckle et al. 2024)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eIreland\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eQualitative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eChildren (n = 7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003ePurposive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eSingle art session facilitated by an art therapist, followed by semi-structured interviews\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 207px;\"\u003e\n \u003cp\u003eCraniofacial condition, Gaucher, dystonia, phenylketonuria, homocystinuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThese studies reviewed offer complementary yet diverse perspective on the psychosocial impact of RDs. \u0026nbsp; Two studies (Siddiq et al. \u0026nbsp;2016; Smits et al. 2022) underscored the emotional toll on caregivers, highlighting advocacy roles and the strain of navigating complex healthcare systems. Siddiq et al. focused specifically on inherited metabolic disorders, whereas Smits et al. examined a wider spectrum of genetic and complex conditions, stressing the importance of interdisciplinary care and empathic communication (Pierre-Louis et al. 2017) explored parental experiences in neurofibromatosis, identifying compounded stress from stigma and body symptomatology. Dellenmark-Blom et al. (2023) employed a mixed-methods approach, combining validated quantitative tools (SDQ, PedsQL 4.0) with qualitative results to generate robust evidence on the psychosocial consequences of long-gap oesophageal atresia. Buckle et al. (2024) synthesised children\u0026rsquo;s perspectives across two studies, showing how social exclusion and creative outlets such as art therapy shape emotional expression, resilience, and identity. In tandem, these studies reveal overlapping themes of emotional distress, caregiver burden, and systemic gaps in support, while their methodological and population-specific variations enrich the understanding of RD experiences.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eEmotional Distress and Mental Health Challenges\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eChildren and adolescents with RDs faced heightened emotional distress compared to their peers, driven by the chronic, unpredictable, and often debilitating nature of their conditions. Across all studies, common themes included anxiety, depression, social isolation, and low self-esteem, underscoring the broad psychosocial impact of RDs. Dellenmark-Blom et al. (2023) reported that 46% of with long-gap oesophageal atresia (LGEA) experienced significant mental health difficulties, including hyperactivity, inattention, and challenges forming peer relationships, all of which reduced health-related quality of life (HRQoL). Physical comorbidities, such as asthma and sleep disturbances, further compounded psychological struggles.\u003c/p\u003e\n\u003cp\u003eSocial exclusion was consistently described, with children excluded from sports, school events, and peer activities due to physical limitations, frequent hospitalisations, or lack of understanding from peers and educators (Buckle et al. 2024). The tension between wanting to \u0026ldquo;fit in\u0026rdquo; while \u0026ldquo;feeling different\u0026rdquo; created significant emotional strain, fuelling anxiety and diminished self-worth. Stigma, particularly for those with visible symptoms or medical equipment, intensified these difficulties, leading to bullying, shame, and barriers to forming meaningful relationships (Pierre-Louis et al. 2017; Buckle et al. 2024).\u003c/p\u003e\n\u003cp\u003eAdolescents were identified as particularly vulnerable, struggling to balance the dual demands of managing their condition while striving for independence and social integration (Buckle et al. 2024). Gender-based differences were also noted, with boys showing higher rates of emotional and social difficulties \u0026nbsp;(Dellenmark-Blom et al. 2023). Academic challenges further compounded these pressures, as repeated absences disrupted learning and peer connections, perpetuating cycles of underachievement and isolation (Siddiq et al. 2016).\u003c/p\u003e\n\u003cp\u003eWhile these findings revealed significant psychological vulnerabilities, several reviewed studies also emphasised the lack of specialised mental health resources tailored to the needs of children with RDs (Smits \u003cem\u003eet al\u003c/em\u003e. \u0026nbsp;2022; Pierre-Louis \u003cem\u003eet al\u003c/em\u003e. 2017). The absence of early psychosocial interventions left many children without adequate support, highlighting a critical gap in care.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCaregiver Insights and Stress\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCaregivers of children with RDs face profound physical, emotional, and financial burdens that shape their well-being and caregiving capacity. Across all included studies, caregiving was described as an all-encompassing role requiring constant advocacy, care coordination, and management of complex medical needs, often at the expense of caregivers\u0026rsquo; health, careers, and social lives.\u003c/p\u003e\n\u003cp\u003ePierre-Louis et al. (2017) documented the heightened stress levels experienced by parents of children with neurofibromatosis, emphasising the emotional toll of stigma linked to visible symptoms. Caregivers reported isolation, helplessness, and fatigue, noting that their distress directly affected their ability to provide consistent care and influenced broader family dynamics. Smits et al. (2022) highlighted similar challenges, including navigating fragmented healthcare systems, coping with uncertainty, and balancing caregiving with work and family responsibilities. Caregivers expressed frustration at the lack of interdisciplinary support and empathic communication, identifying the need for family-focused models of care that address both medical and psychosocial needs.\u003c/p\u003e\n\u003cp\u003eSiddiq et al. (2016) explored the distinctive challenges of caring for children with inherited metabolic diseases, where parents not only managed strict dietary and treatment regimens but also ffound themsleves requently educated healthcare professionals unfamiliar with their child\u0026rsquo;s condition.\u0026nbsp;This parental sense of advocacy extended to ensuring that their children received appropriate accommodations in educational and social settings, further straining caregivers\u0026rsquo; mental and emotional resources\u003c/p\u003e\n\u003cp\u003eFinancial pressures were reported across all studies, including costs for treatments, travel, adaptive equipment, and lost income due to caregiving demands. Smits et al. (2022) and Siddiq et al. (2016) highlighted how financial strain compounded emotional distress and restricted access to support services. Caregivers also prioritised their child\u0026rsquo;s needs over their own, leading to strained family relationships (Pierre-Louis et al. 2017; Smits et al. 2022).\u0026nbsp;The absence of structured support systems often meant that caregivers bore the brunt of these challenges alone, further deepening their sense of fatigue and emotional exhaustion.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eCoping Mechanisms and Resilience Strategies\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eDespite the abovementioned challenges, families demonstrated remarkable resilience, employing various coping strategies to navigate their circumstances. Siddiq et al. (2016) reported that caregivers frequently engaged in proactive information-seeking behaviours, turning to online resources, support groups, and advocacy organisations. These efforts fostered empowerment and emotional resilience, while planning and problem-solving strategies helped caregivers maintain a sense of control in managing uncertainty.\u003c/p\u003e\n\u003cp\u003eFor children, creative outlets such as art therapy provided powerful means of coping. Buckle et al. (2024) highlighted the therapeutic value of artistic expression, which not only facilitated emotional processing but also enabled children to articulate their experiences and strengthen identity formation. Such activities often enhanced communication within families, promoting stronger emotional bonds. Structured interventions, including family-centred counselling and resilience training, were also shown to equip families with practical tools to manage stress, improve communication, and enhance psychological flexibility (Buckle et al. 2024).\u003c/p\u003e\n\u003cp\u003eSocial support networks emerged as another protective factor. Smits et al. (2022) emphasised the importance of connections with other parents through formal groups or informal community networks, which provided practical advice, validation, and solidarity. Similarly, Pierre-Louis et al. (2017) noted the potential of resilience-based interventions, particularly when delivered in accessible formats tailored to family needs.\u003c/p\u003e\n\u003cp\u003eCollectively, these studies underline that while individual coping strategies and peer networks are essential, they remain insufficient in isolation. Sustained resilience requires systemic support through integrated care models that combine medical, psychological, and social interventions to address the multifaceted challenges of RD families.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCommunication and Support Needs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEffective communication between healthcare providers and families emerged as a critical theme across all studies. Caregivers frequently reported feeling unheard or dismissed in clinical encounters, which exacerbated stress and hindered their ability to advocate for their children (Pierre-Louis et al. 2017; Smits et al. 2022). These difficulties were often compounded by fragmented care systems requiring families to coordinate across multiple providers. Both studies emphasised the importance of clear, empathic, and transparent communication to build trust and improve care satisfaction.\u003c/p\u003e\n\u003cp\u003eSiddiq et al. (2016) further highlighted caregiver dissatisfaction with non-specialist providers unfamiliar with the complexities of RDs. This lack of expertise contributed to delays and inconsistent care, intensifying emotional and logistical burdens.\u0026nbsp;Siddiq \u003cem\u003eet al\u003c/em\u003e. (2016) underscored the need for enhanced training in RD management, particularly in general healthcare settings where caregivers often encounter the greatest frustrations.\u003c/p\u003e\n\u003cp\u003eInterdisciplinary care models were consistently identified as best practice for bridging communication gaps. Smits et al. (2022) and Pierre-Louis et al. (2017) both highlighted the value of integrated models that combine medical, psychological, and social support. Such approaches ensure consistent messaging, streamline care delivery, and reduce the strain of navigating fragmented systems.\u0026nbsp;interdisciplinary care teams that include geneticists, psychologists, social workers, and educators, were shown to foster a more holistic approach to care, addressing both the medical and psychosocial dimensions of RD management.\u003c/p\u003e\n\u003cp\u003eEducational contexts also shaped communication experiences. Buckle et al. (2024) identified significant gaps in awareness among educators and peers, which contributed to inadequate accommodations and social exclusion for children with RDs. Parents often assumed the role of mediators, explaining their child\u0026rsquo;s condition to secure basic support. Tailored educational programs, peer-awareness initiatives, and teacher training were highlighted as essential for reducing stigma and fostering inclusivity, helping children feel recognised and valued within their school communities.\u003c/p\u003e\n\u003cp\u003eBeyond clinical and educational contexts, communication was also linked to access to reliable information. Smits et al. (2022) stressed the importance of providing families with access to reliable information about their child\u0026rsquo;s condition, treatment options, and available resources. The integration of digital tools, such as telehealth platforms and online educational materials, were identified as a promising avenue for enhancing communication and providing families with the information they need to navigate complex care systems. Pierre-Louis et al. (2017) further suggested that resilience-based interventions delivered via live video formats could help bridge geographical and logistical gaps, making support services more accessible to a wider range of families.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eSynthesis of Key Findings\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe results from the individual studies were synthesised by juxtaposing results in a table (Table 2) and being reviewed independently by two researchers (GF and DVF) until a consensus was reached. Due to the highly qualitative nature of the included studies, meta-analysis or other types of quantitative syntheses were not possible.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSynthesises the Key Findings from the Studies, Highlighting the Overarching Themes and Insights Gained from the Analysis.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"606\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 522px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSynthesis of Key Findings\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e(Siddiq et al. 2016)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 522px;\"\u003e\n \u003cp\u003e\u0026ldquo;New normal\u0026rdquo;: Adapting to the daily complexities of parents/caregivers managing their children\u0026apos;s conditions. \u003cstrong\u003eThese findings highlight the need for improved coordination of care and support systems to address both the social and healthcare needs of families navigating the complexities of IMD management.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e(Pierre-Louis et al. 2017)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 522px;\"\u003e\n \u003cp\u003eParents experienced significant emotional and physical health challenges due to the demands of caregiving, with existing interventions for parents of children with chronic illnesses proving ineffective in alleviating such burdens. \u003cstrong\u003eFindings emphasised\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;the need for accessible delivery methods like live video formats to enhance participation and support among geographically dispersed families.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e(Dellenmark-Blom et al. 2023)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 522px;\"\u003e\n \u003cp\u003eThis study indicates that nearly half (46%) of children with LGEA experience mental health challenges, as reported by parents. Common concerns include difficulties in forming peer relationships and symptoms related to hyperactivity and inattention. Boys appeared to be more vulnerable, with contributing factors such as asthma and sleep issues playing a significant role. \u003cstrong\u003eThese mental health challenges were associated with a decline in health-related quality of life, underscoring the need for comprehensive follow-up care.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e(Buckle et al. 2024)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 522px;\"\u003e\n \u003cp\u003eIdentified two primary themes related to the lived experiences of children with RDs: Knowledge and understanding of their conditions and the tension between \u0026ldquo;fitting in\u0026rdquo; versus \u0026ldquo;feeling different\u0026rdquo;. Overall, while hospital experiences were often viewed positively, social life was significantly impacted, \u003cstrong\u003ehighlighting a need for greater awareness and support in school settings to foster inclusivity and understanding among peers.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e(Smits et al. 2022)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 522px;\"\u003e\n \u003cp\u003eThe study investigated the common needs of parents caring for children with RDs, identifying eight primary themes: Family-focused care, coping with uncertainty, empathic communication, practical support, information, psychological support, interdisciplinary care, and social support. \u003cstrong\u003eFindings highlight the necessity for a holistic, interdisciplinary approach in paediatric care, addressing both the medical and psychosocial needs of families.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 84px;\"\u003e\n \u003cp\u003e(Buckle et al. 2024)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 522px;\"\u003e\n \u003cp\u003eThis study elucidated that children with RDs encounter significant psychosocial challenges, including feelings of isolation and concerns regarding their identity. These aspects are notably influenced by the presence of supportive relationships with peers and family members. \u003cstrong\u003eFurthermore, the findings underscore the necessity for holistic and child-centred research approaches (e.g., art) that honour and actively engage children as experts in their own lived experiences.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eRisk of Bias\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo researchers (GF and DVF) independently reviewed the included studies, ensuring that each study met the inclusion criteria. After evaluating the methodological rigour and addressing potential biases, it was determined that all six studies fit the established criteria, and none were excluded from the analysis. The MMAT provided a comprehensive framework for evaluating the quality of the studies, and all studies were considered to have met the required standards for inclusion in the review.\u003c/p\u003e\n\u003cp id=\"_Toc185709628\"\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMixed Method Appraisal Tool (MMAT) Assessment of Study Quality\u0026nbsp;(\u0026ldquo;Y\u0026rdquo; = 1; \u0026ldquo;N\u0026rdquo; = 0)\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003eFirst Author, Publication Date\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003eAll \u0026nbsp; \u0026nbsp; Studies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003eQualitative studies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003eMixed Methods\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eS1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eS2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e2.1\u0026nbsp;\u0026ndash; 4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003eSiddiq (2016)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"6\" valign=\"top\" style=\"width: 56px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003ePierre-Louis (2017)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003eDellenmark-Blom (2023)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003eBuckle (2024)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003eSmits (2022)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003eBuckle (2024) Art Method\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eY\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eY Yes, N No, C Can\u0026apos;t determine\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis systematic review provides a detailed examination of the psychosocial and mental health challenges encountered by children and adolescents with RDs and their caregivers. The findings reveal recurring themes, including emotional distress, caregiver burden, coping strategies, and the significance of effective communication. These insights not only reinforce but also expand upon existing literature, presenting a nuanced understanding of the multifaceted challenges faced by RD families. By comparing the reviewed studies with prior research, this discussion elucidates consistencies, discrepancies, and evolving perspectives in the field.\u003c/p\u003e\n\u003cp\u003eThis systematic review revealed that children and adolescents with RDs endure heightened levels of anxiety, depression, and social isolation. These psychological challenges are often attributed to the chronic and debilitating nature of their conditions, which impose frequent hospitalisations, physical limitations, and barriers to participating in typical childhood activities. Furthermore, it also indicated that these children and adolescents with RDs experience a potentially complex symptomatology associated with hyperactivity, social development, identity formation, struggles in forming peer relationships, the desire to “fit in” and the experience of “feeling different” (Buckle et al. 2024; Dellenmark-Blom et al\u003cem\u003e.\u003c/em\u003e2023). These observations align with earlier findings (Uhlenbusch et al. 2019 which emphasise the prevalence of psychological distress in RD populations, and the relationship between stigmatisation and its detrimental impact on self-esteem. However, in addition to existing literature, this systematic review highlights the distinct ways in which these challenges manifest across different contexts.\u003c/p\u003e\n\u003cp\u003eThis study further emphasised the impact of RDs on caregivers, who shoulder immense emotional, physical, and financial burdens, and taking on an invaluable advocacy role especially when navigating within non-specialised healthcare systems with already overstretched budgets. This further necessitates efficient access to psychological support, family-focused care, and empathic communication from healthcare providers, highlighting the importance of peer support networks for caregivers to prevent social isolation (Smits et al. 2022; Siddiq et al. 2016). These findings corroborate earlier research by Dellve et al. (2006) which underscored the significant stress and fatigue experienced by caregivers. Furthermore, previous research has also highlighted the financial strain of managing medical expenses and specialised treatments (Anderson et al. 2013) During the systematic process of reviewing included studies, the authors identified a consistent pattern of helplessness experiences by caregivers. However, Chung et al. (2022) reported that RDs are an emerging public health priority. This contrasts with the findings elucidated from our results, which might imply a lack of specific resources for specialised services working with RD patients. This might inform the development of innovative services for RD families given the potential stigma associated with RDs (Baynam et al. 2024).\u003c/p\u003e\n\u003cp\u003eAs outlined in this systematic review, providing temporary relief, and fostering resilience is imperative for caregivers of children and adolescents with RDs, and emphasised the importance of proactive information-seeking behaviours and advocacy (Buckle et al. 2024; Siddiq et al. 2016). This aligned with previous findings in the literature describing coping strategies as integral to how families navigate the challenges associated with RDs, and the importance of emotional support from social networks, creative outlets, family-centred counselling, resilience training, and mindfulness practices to manage stress (Dellve et al. 2006; Anderson et al. 2013). In keeping with the notion of caregiver support, research has also emphasised the benefits of online communities to reduce isolation and foster a sense of belonging (Ashtari and Taylor, 2022). This systematic review, in conjunction with previous research, delineates how integrating the aforementioned approaches may allow healthcare systems to better address the holistic needs of RD families. It is understandable that RDs may pose as a potentially traumatic factor in one’s life (Zhang\u0026nbsp;2023). Previous research has also identified that such traumatic factors may foster an emotional connection between loved ones (Raz et al. 2024). Therefore, this may serve as a protective factor for RD families, notwithstanding the need for further resources to avoid parental burnout and excessive burden of care.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCommunication has been highlighted as a crucial theme especially between healthcare providers and families, which serves to minimise caregiver burnout and bilaterally ameliorate the professional-caregiver alliance (Smits et al. 2022; Pierre-Louis et al. 2017). Inconsistencies in information provision and a lack of transparency were also reported as perpetuating the subjective dissatisfaction among caregivers, especially towards non-specialised healthcare services (Siddiq et al. 2016). This mirrors previous reports describing the limitations associated with fragmented care pathways, and the importance to develop the necessary frameworks for integrating medical, emotional, and social support, thereby improving care coordination and outcomes (Richardson et al. 2024).\u003c/p\u003e\n\u003cp\u003eThe frequently encounter stigma by children and adolescents in educational and social settings has been heavily implicated in this systematic review, including the importance of fostering inclusivity within schools to mitigate these challenges. This further highlighted the central role of stigma in shaping the psychosocial experiences of RD patients and caregivers (Buckle et al. 2024). These findings align with previous research identifying a lack of understanding among educators as a key barrier to social integration (García-Perales et al. 2022) and the importance of utilising systematic efforts (and not solely individual interventions) to promote awareness and inclusivity (Belzer et al. 2022). Furthermore, Currie and Szabo (2018) documented the academic and social disruptions caused by frequent absences and limited support in schools. A gradual transition towards a holistic educational environment has been frequently reported (Sankar, 2025).\u0026nbsp;However, from the results generated in this systematic review, this does not seem to be the case for students with RDs. The lack of educational institutions supporting children and adolescents with RDs has been frequently mentioned, with an emphasis on the lack of tailored support systems within schools, contributing to feelings of exclusion and academic underachievement (Buckle et al. 2024). School environments can act as a microcosm of societal attitudes toward individuals with RDs, and the findings in this review here reaffirm that perspective. Efforts to train educators in understanding the unique challenges faced by RD patients, coupled with peer-awareness programs, can foster a more inclusive environment that enhances both educational and social outcomes (Röjvik et al. 2023).\u003c/p\u003e\n\u003cp\u003eFinancial strain in RD families was also a recurring theme in this review, particularly for caregivers tasked with managing costly medical treatments and adaptive equipment (Siddiq et al. \u0026nbsp;2016). Domaradzki et al. (2025)\u0026nbsp;has also reported such financial challenges associated with RD care, which not only exacerbate emotional stress but also impact the caregivers’ ability to provide consistent and effective support. This underscores the need for policy interventions that address these economic disparities, including subsidies for medical expenses and expanded access to respite care, which may help alleviate caregiver strain and improve the struggling family dynamic (Somanadhan et al. 2025)\u003c/p\u003e\n\u003cp\u003eAll the studies included in this systematic review highlighted the importance of addressing disparities in access to care. While previous research (Forman et al. 2012) had acknowledged gaps in RD healthcare services, this systematic review further explores how these disparities manifest in day-to-day challenges for families, highlighting the fragmentation of healthcare systems secondary to the lack of coordinated care and specialised pathways (Smits et al. 2022). Healthcare models supporting integration of care are crucial in such situations (Taruscio et al. 2015). One study in this systematic review (Pierre-Louis et al. 2017) greatly focused on how telemedicine and digital platforms could help bridge gaps in the access of care, particularly for geographically isolated families. This underscores the potential for innovative technologies to address long-standing barriers in RD management. Overall, there was a consensual agreement in this systematic review that the psychosocial difficulties of caregivers accentuate the urgent need for mental health interventions tailored to their needs. This might mitigate the physical and logistical challenges, including emotional turbulence, that families experience by introducing more logistically friendly digital measures of healthcare.\u003c/p\u003e\n\u003cp\u003eTo the authors’ knowledge, this represents the first systematic review to specifically examine the psychosocial impact and mental health challenges of RDs families, including the need for a paradigm shift in the way healthcare systems, educational institutions, and social policies address the challenges faced by these families. The review highlights the critical role of interdisciplinary and family-centred care in bridging the gaps between medical, psychological, and social support services. It also emphasises that systemic barriers, such as fragmented healthcare delivery, inadequate educational support, and financial strain, not only exacerbate the emotional and psychological burdens of RD families but also hinder their overall quality of life. The resilience displayed by RD families presents valuable insights into strategies that work, such as peer support, creative therapies, and advocacy. However, the current reliance on individual coping mechanisms reflects the absence of robust systematic frameworks. These findings should serve as a call to action for healthcare providers, educators, and policymakers to prioritise equitable access to comprehensive, coordinated care models that address the multifaceted needs of RD families. This systematic review contributes to the growing recognition that addressing the psychosocial dimensions of RDs is not only a healthcare challenge but also a critical step toward achieving broader social justice and inclusion.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eDespite the insights provided by this systematic review, several limitations must be acknowledged. Only six studies met the inclusion criteria, reflecting the scarcity of research on the psychosocial experiences of RD families. While this highlights the importance of the review in addressing a gap in the literature, the small number of studies limits the generalisability of the findings.\u003c/p\u003e\n\u003cp\u003eAs most included studies were qualitative, the review followed an interpretivist epistemological paradigm. Although this reduces generalisability, it allowed for a deeper exploration of lived experiences. The inclusion of one mixed-methods study introduced a post-positivist perspective, partially enhancing generalisability and compensating for methodological limitations. The predominance of qualitative approaches is appropriate given the complexity of psychosocial experiences. However, the absence of longitudinal studies limits understanding of how emotional distress and coping strategies evolve over time and restricts causal inference.\u003c/p\u003e\n\u003cp\u003eDespite these limitations, this review offers important strengths. It synthesises evidence that provides meaningful insights into the psychosocial burden experienced by children with RDs and their caregivers, emphasising the need for improved support systems. Key themes, including emotional distress, caregiver burden, and communication challenges, were identified, offering a foundation to inform future research, interventions, and policy development.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eFuture Implications\u0026nbsp;\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eHealthcare systems must prioritise the development of integrated, family-centred care models that provide medical, psychological, and social support within a unified framework. Telehealth and digital tools should be utilised to enhance accessibility, particularly for families in remote or underserved areas, and to improve communication and care coordination across healthcare teams. Subsidies for medical treatments, adaptive equipment, and travel for specialist care can significantly reduce the financial burden on families. Expanding insurance coverage and increasing access to respite care programmes for caregivers are further measures that may mitigate stress and improve overall well-being. Policymakers should also advocate for increased funding for RD research and caregiver support programmes, recognising the long-term benefits of these investments for families and healthcare systems.\u003c/p\u003e\n\u003cp\u003eResilience-building interventions are essential to enhance the emotional and psychological well-being of families affected by RDs. Expanding access to family counselling, peer support networks, and mindfulness-based interventions may help caregivers and children manage stress and strengthen coping mechanisms. Non-traditional therapeutic approaches, such as art therapy, offer valuable opportunities for emotional expression and can support family relationships. Digital platforms may also be leveraged to provide online peer support and educational resources, fostering community connection and empowerment.\u003c/p\u003e\n\u003cp\u003eTraining healthcare professionals is imperative to improve understanding of the unique challenges associated with RDs and to promote empathetic communication, thereby strengthening trust and caregiver experiences. Educational systems also play a critical role in supporting children and adolescents with RDs. Tailored training programmes for educators are recommended to address individual needs and ensure appropriate accommodations that support academic progress and social integration. Peer-awareness initiatives and anti-stigma programmes within schools are equally important in fostering inclusive environments and reducing isolation. Public education campaigns and community-based initiatives can extend these efforts to address societal stigma.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis systematic review highlights the substantial psychosocial and mental health challenges experienced by RD families, underscoring the urgent need for targeted interventions across research, clinical practice, and policy. Children with RDs face significant emotional distress, including anxiety and depression, driven by physical limitations, frequent hospitalisations, stigma, and social exclusion. Adolescents appear particularly vulnerable as these challenges intersect with identity formation and social integration, resulting in reduced quality of life.\u003c/p\u003e\n\u003cp\u003eCaregivers experience multifaceted burdens, including emotional exhaustion, financial strain, and disruption to personal and professional lives. Many adopt advocacy roles to navigate fragmented healthcare systems, increasing stress and burnout, while the rarity of conditions often leads to social isolation and limited peer support. Despite these challenges, families demonstrate notable resilience through proactive coping strategies such as information-seeking, mindfulness, peer support, and creative interventions like art therapy. However, these strategies remain insufficient without robust systemic support.\u003c/p\u003e\n\u003cp\u003eThe findings reveal critical gaps in healthcare communication, interdisciplinary coordination, educational accommodations, and financial support. By synthesising limited but meaningful evidence, this review contributes to an under-researched field and provides a foundation for future research and service development. Further longitudinal and quantitative studies are needed to better understand evolving psychosocial needs and to inform equitable, inclusive interventions for RD families.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRare Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eQuality of Life\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eQOL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHealth Related Quality of Life\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHQoL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStrengths and Difficulties Questionnaire\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSDQ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGeneric Health Related Quality of Life\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePedsQL 4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCondition Specific Health related Quality of Life\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eLong gap oesophageal atresia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEA-QOL\u003c/p\u003e\n \u003cp\u003eLGEA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConsent to Participate Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent was not required due to nature of this study\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics Approval by Learna/University of South Wales\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable due to nature of this study\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003e\u003cstrong\u003eStatements and Declarations\u003c/strong\u003e\u003c/h4\u003e\n\u003cp\u003eNo competing interests\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/h4\u003e\n\u003cp\u003eUniversity of South Wales\u0026nbsp;\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eGF- Main ResearcherDVF- Second ResearcherKN- Supervisor\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKole A, Faurisson F. 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Public Health Genomics. 2014;18(1):20\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1159/000365897\u003c/span\u003e\u003cspan address=\"10.1159/000365897\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Rare Diseases](https://link.springer.com/journal/44162)","snPcode":"44162","submissionUrl":"https://submission.nature.com/new-submission/44162/3","title":"Journal of Rare Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Rare Diseases, Child, Adolescent, Mental Health, Caregiver Burden, Quality of Life ","lastPublishedDoi":"10.21203/rs.3.rs-9253757/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9253757/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAim\u003c/p\u003e\n\u003cp\u003eThis systematic review aims to explore the psychosocial impact and mental health challenges of childeren and adoloscents with rare diseases (RDs) and their families. It examines their daily challenges, emotional distress, coping mechanisms, and resilience strategies while identifying systemic gaps in care and support.\u003c/p\u003e\n\u003cp\u003eMethods\u003c/p\u003e\n\u003cp\u003eThe review adhered to PRISMA guidelines, employing a comprehensive search of databases; Google Scholar, PubMed and PsycINFO. Studies were selected based on predefined criteria and appraised for quality using the Mixed Methods Appraisal Tool (MMAT). Both qualitative and quantitative studies were included, focusing on mental health challenges, caregiver stress, coping mechanisms, and resilience strategies.\u003c/p\u003e\n\u003cp\u003eResults\u003c/p\u003e\n\u003cp\u003eChildren and adolescents with RDs face significant emotional distress, including anxiety, depression, and a diminished quality of life, which are exacerbated by physical limitations, frequent hospitalizations, and social exclusion. Meanwhile, their primary caregivers endure profound emotional and financial burdens, compounded by the demands of advocacy roles and navigating fragmented care systems. Although families adopt various coping mechanisms, such as peer\u003c/p\u003e\n\u003cp\u003esupport and creative outlets like art therapy, systemic gaps in psychosocial support and access to interdisciplinary care remain prevalent.\u003c/p\u003e\n\u003cp\u003eConclusion\u003c/p\u003e\n\u003cp\u003eThe findings underscore the need for integrated, family-centred care models that address the multifaceted challenges of living with RDs. By fostering holistic medical, psychological, and social support systems, these models can enhance resilience, reduce the psychosocial burden, and improve the overall quality of life for children with RDs and their care\u003c/p\u003e","manuscriptTitle":"Mental Health Challenges and Psychosocial Impact of Rare Diseases in Children and Adolescents -A Systematic Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-19 07:52:48","doi":"10.21203/rs.3.rs-9253757/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-29T16:20:06+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-18T11:54:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-10T16:27:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"253491267563925320447589974474559009774","date":"2026-04-09T09:46:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"13161871024687658385293794105253777455","date":"2026-04-08T12:39:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-08T10:59:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-06T15:28:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-06T15:28:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Rare Diseases","date":"2026-03-28T15:00:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Rare Diseases](https://link.springer.com/journal/44162)","snPcode":"44162","submissionUrl":"https://submission.nature.com/new-submission/44162/3","title":"Journal of Rare Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"544181b4-0d44-4343-8fe2-4ecf236f877b","owner":[],"postedDate":"April 19th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-04-29T16:20:06+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T09:39:41+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-19 07:52:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9253757","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9253757","identity":"rs-9253757","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}