Case report: Bipolar disorder in Phelan-McDermid syndrome

Case report: Bipolar disorder in Phelan-McDermid syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Case report: Bipolar disorder in Phelan-McDermid syndrome Yuyong Sun, Yong Xia, Qianna Zhi, Pengfei Guo, Wenjing Cui, Xiaoyan Liu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4611416/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Phelan-McDermid syndrome (PMS) is a rare genetic disorder. It involves intellectual disability, delayed language, autism spectrum disorders, motor tone abnormalities, and a high risk of psychiatric symptoms like bipolar disorder. Case presentation We present an 18-year case of a 36-year-old woman with PMS, exhibiting intellectual disabilities, social withdrawal, and stereotyped behavior. Diagnosed with bipolar disorder at 18, she faced treatment challenges, including severe reactions to antipsychotics in 2022, leading to speech and functional regression. Subsequent rehabilitation and comprehensive therapy improved her condition. By 2024, following additional treatment, her symptoms stabilized. Conclusions PMS requires detailed history, genetic testing, and long-term supportive care for effective management. Phelan-McDermid syndrome Bipolar disorder diagnosis Treatment Malignant syndrome Figures Figure 1 Background Phelan-McDermid syndrome (PMS), also known as 22q13.3 deletion syndrome, is a rare neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene on chromosome 22 [1] . Genetic variations in PMS include terminal or interstitial deletions, translocations, mutations, or ring chromosomes [2] . This syndrome is characterized by intellectual disabilities, delayed language development, autism spectrum disorders, and motor tone abnormalities [3] . SHANK3 gene abnormalities increase the risk of mental disorders [4] . Studies indicate that infections, hormonal changes, and life stress can trigger psychiatric symptoms in PMS patients, with psychiatric disorders typically appearing during adolescence or early adulthood [5] . Approximately 54% of PMS patients may meet the criteria for bipolar disorder, and about half may experience behavioral regression [3] .We report a 36-year-old female PMS patient with delayed mental development from childhood and recurrent manic episodes from age 18. Her treatment was complicated by severe reactions, including neuroleptic malignant syndrome, leading to regression in speech and daily living skills. After a year of treatment, some improvement was noted, but manic symptoms recurred, necessitating further treatment. Case Presentation The patient is a 36-year-old female. Her family reported that she could only point at objects and make sounds at the age of 2, called her mother at age 3, and began walking at that time. In early childhood, she was often silent, seldom speaking, and had no active social interactions with those around her. When she started elementary school, her academic performance was poor; she could not perform addition and subtraction within 100 and could not leave the house alone. Her daily life required family assistance. The family did not take her to the hospital for an examination, and due to her inability to cope with studies, she dropped out after the sixth grade. Living under the family's care, she could dress herself, eat, and follow simple instructions. At age 18, she first exhibited noticeable emotional instability: she became talkative, spoke grandiosely, she was excessively excited and screamed frequently, sleeping only 2-3 hours per day yet appeared very energetic, and demanded her family to buy many things for her. These episodes recurred several times, each lasting about a month, followed by periods of reclusive and sparse speech. In the same year, she was hospitalized for one month, with a Wechsler Intelligence Scale score of 54, diagnosed with "1. Mental retardation with significant behavioral defects requiring attention or treatment; 2. Bipolar disorder, currently in a manic episode without psychotic symptoms." Treatment included Clozapine and Oxcarbazepine, though the family could not provide specific dosages; she discontinued medication after about six months. When her condition was stable, her mood and behavior were stable, her speech remained simple, and she lived independently with family assistance. At 23 years old, she got married and gave birth to a daughter at 24 years old. After childbirth, her condition relapsed once: she became hyper-excited, talkative, scattered in speech, spent excessively, and demanded that the family buy large amounts of toilet paper. After another hospitalization and two months of treatment, her condition improved, and she continued treatment with Clozapine (25-75 mg/day) until June 2021, when she relapsed again, displaying irritability, excessive talking with simple words, shouting, walking around the house, and sleeplessness at night. In August 2021, she was hospitalized again locally and treated with Lurasidone (40-80 mg/day), Clozapine (25-100 mg/day), Oxcarbazepine (1.2 g/day), and Lorazepam (2 mg/day), but her condition remained poorly controlled, with persistent emotional instability and shouting. By December 2021, she became very sluggish and had a stiff walking posture. Doctors gradually discontinued Clozapine and Lurasidone, switching her to Olanzapine (5-20 mg/day) over two weeks. However, her condition worsened, sleep deteriorated, she screamed continuously at night, her limbs became rigid, she held her hands up, and swallowing became difficult. On January 13, 2022, her condition suddenly worsened: she became rigid, continuously screamed, sweated profusely, her body temperature rose to 38.8°C, blood pressure spiked to 170/110 mmHg, heart rate increased to 100-130 bpm, and she experienced incontinence. Her right hand became claw-like, muscle tone significantly increased, and she was in a state of rigid flexion spasms with a creatine kinase level of 11154 U/L. On January 17, 2022, she was admitted to our hospital. Upon admission, she was unconscious, disoriented, rigid, unable to speak, with tense facial expressions, unable to eat independently, had difficulty swallowing, and continuously screamed "ah, ah." Detailed lab results are in the attached table 1. She was diagnosed as "1. Neuroleptic malignant syndrome; 2. Mental retardation with significant behavioral defects requiring attention or treatment." Since she was unconscious and not exhibiting mania, a bipolar disorder diagnosis was not made at this time. During hospitalization, she was unable to eat and was incontinent, so a nasogastric tube and urinary catheter were placed. Olanzapine was gradually discontinued and Diazepam mainline (10 mg/day) was administered to alleviate tension, combined with 10 sessions of MECT (modified electroconvulsive therapy). Lung infection was detected at admission, treated with Cefoperazone-Sulbactam (3.0 g Q12h), administer fluid rehydration therapy. After the first week, the patient had no fever, her heart rate, blood pressure, but she remained shouting. By the 14th day, she was still unaware and in a state of rigid flexion spasms, we performed a lumbar puncture on the patient, including routine, biochemical, and autoimmune encephalitis panel, all of which were negative. By the 20th day, her lung infection had mostly resolved. On the 24th day, her consciousness began to clear, she responded to a video of her daughter Diazepam was replaced with Lorazepam (2 mg/day). Although she's a little more emotionally stable, the most severe problems were her inability to perform daily self-care, feed herself, void independently, and the presence of increased muscle tone with sustained rigid flexion spasms. The family members transferred her to a general hospital for continued rehabilitation for an additional five months. Table 1 Laboratory examination Test time test project name test result January 17, 2022 Blood routine examination WBC 4.37×10 9 /L RBC 3.91×10 9 /L HGB 106g/L PLT 26710 9 /L↑ January 17, 2022 blood biochemistry ALT 62.5U/L↑ AST 136.3U/L↑ CK 11154U/L↑ CK-MB 218.21U/L↑ January 18, 2022 Blood gas analysis, female tumor markers, normal thyroid function。 normal January 19, 2022 Head MRI: Slight vascular origin white matter high signal may be seen in both lateral ventricles, Fazekas grade 1. EEG: Increase in fast waves. February 1, 2022 Routine cerebrospinal fluid examination, cerebrospinal fluid biochemistry, autoimmune encephalitis antibodies. normal February 12, 2022 Blood routine examination WBC5.08×10 9 /L RBC3.95×10 9 /L HGB134g/L PLT192/L February 12, 2022 blood biochemistry ALT 16.3U/L AST 19.3U/L CK 413U/L↑ CK-MB 15.9U/L February 21, 2022 Blood routine examination WBC5.92×10 9 /L RBC3.95×10 9 /L HGB 124g/L PLT 212/L February 21, 2022 blood biochemistry ALT 17.1U/L AST 22.1U/L CK 263U/L↑ CK-MB 17.74U/L During the patient's hospitalization at the rehabilitation hospital, considering her developmental delay and recurrent manic episodes, along with a deterioration in life skills and persistent high muscle tone in her limbs, whole-exome sequencing was performed in April 2022, identifying a SHANK3 gene mutation c.3865dup associated with her phenotype，See details in Figure 1. The diagnosis was Phelan-McDermid syndrome. She was treated with Lithium carbonate sustained-release tablets (0.3-0.6g/day) in combination with rehabilitation therapy and was discharged home for continued treatment in July 2022. At discharge, her mood was more stable than before, and she could urinate and defecate independently, allowing the removal of the urinary catheter. However, she still had slow swallowing and required a nasogastric tube, could not speak a complete sentence, occasionally said "daughter" or "mom," and sometimes screamed "ah ah." She lay in bed all day, and community healthcare workers regularly visited to care for her nasogastric tube. By November 2022, there was a significant improvement in her condition: her mood gradually stabilized, she could again speak simple words to her family, slowly eat independently, and her nasogastric tube was removed. However, she still had elevated muscle tone, walked unsteadily, and easily fell when walking. Her nutritional status improved, and she gained 20 pounds eleven months after discharge. It took 13 months for her walking instability symptoms to improve significantly. During this period, she continued to receive Lithium carbonate (0.6g/day) treatment and could manage her personal hygiene with family assistance. Her condition remained basically stable. In January 2024, She had a relapse. For about a week, she suddenly became very excited, talked loudly and continuously, yelled, cursed her family, and smashed objects. She often made sexually suggestive remarks, slept only 2-3 hours at night, and was still very energetic during the day, running around the house non-stop. She was admitted to our hospital for the second time in February 2024. The physical examination showed no obvious abnormalities, and she showed signs of manic syndrome. All laboratory tests were normal.The Bech-Rafaelsen Mania Rating Scale (BRMS) score was 26. Based on her complex medical history, psychiatric examination, and lab results, the diagnoses upon this admission were: 1. Intellectual disability with significant behavioral defects requiring attention or treatment; 2. Bipolar disorder, currently manic without psychotic symptoms; 3. Phelan-McDermid syndrome. For treatment, considering her history of multiple manic episodes, the occurrence of neuroleptic malignant syndrome during treatment two years ago, the subsequent deterioration in speech and motor skills, and the difficulty in regaining these skills over nearly 11 months of rehabilitation, we reviewed the literature and held multiple discussions. It was concluded that patients with Phelan-McDermid syndrome are very sensitive to antipsychotics, necessitating low doses [6] . In this treatment, we used Olanzapine 1.25-5mg /day + Lithium carbonate sustained-release tablets 0.6-0.9g/day to help stabilize her mood. For severe agitation, temporary intramuscular injections of Eszopiclone 2-4mg were administered. Simultaneously, with pharmacological treatment, we provided psychological counseling and comfort therapy, communicating with the patient 2-3 times daily for about 15 minutes, teaching her repeatedly not to shout or behave aggressively. Her condition significantly improved about two weeks into hospitalization. The day before discharge, her BRMS score was 6. No severe side effects like neuroleptic malignant syndrome occurred during this treatment. Follow-up two months later showed her mood was stable. The medication combination of Olanzapine(5mg/day) and Lithium carbonate sustained-release tablets (0.9g/day)was effective. Detailed diagnosis and treatment processes are documented in Table 2. Figure 1 insert here Table 2 Patient disease course diagnosis and treatment timeline table. 2-3 years old Late speech development, late walking development, will not actively contact the people around 8-13 years old Learning difficulties, poor grades, need family assistance in personal life such as tying shoelaces, sixth grade elementary school suspension due to learning difficulties 18 years old For the first time, there are hyperactive screaming, more words, less sleep, like to buy things, energy and other behaviors Merriam-webster Intelligence score 54 Inpatient diagnosis: 1, mental retardation, significant behavioral deficits requiring attention or treatment; 2. Bipolar disorder, currently a manic episode without psychotic symptoms, has received "clozapine, oxcarbazepine" and other treatments Improved after treatment, normal mood stable. But repeated manic episodes. Usually, personal life and speech are simple, and personal life needs the assistance of family members 23 years old get married emotionormal 24 years old Give birth to a daughter, postpartum 1 month when the disease attack 1 time, hyper language, spend more money, buy a lot of toilet paper He was treated with clozapine After 2 months, the patient's mood gradually stabilized, and long-term treatment with clozapine tablets 25-75mg/day. 33 years old (June 2021) Patients with recurrent disease, hyperactivity, excessive speech, screaming, sleep loss, high energy Hospitalized for treatment of "Lurasidone 40-80mg/ day, clozapine tablet 25-100mg/ day, oxazepine 1.2/ day, Lorazepam 2mg/ day" The patient's condition did not improve well, emotional excitement, frequent high-pitched screaming 33 years old (December 2021) The patient's movements become sluggish and postural behavior becomes rigid Doctors stop "clozapine lurasidone" and replace it with "Olanzapine 5-20mg/ day" within 2 weeks. Sleep becomes worse, stiffness becomes more severe, and swallowing becomes difficult 34 years old (January 2022) The patient's body rigidity was more obvious, the body temperature was 38.8℃, sweating, increased blood pressure, increased heart rate, urinary and bowel incontinence, body rigidity and distortion, and the right hand was rigid and bent like chicken feet 34 years old (January 17, 2022) The patient has confusion, disorientation, rigidity, difficulty swallowing, and occasional screaming The patient came to our hospital for emergency treatment. After hospitalization, the treatment of olanzapine was discontinued, fluid replenishing support, diazepam needle 10mg/ day intravenous drip treatment, combined with MECT treatment The symptoms of fever and sweating were relieved after 1 week of hospitalization, and the symptoms of tension and rigidity were relieved after 2 weeks of hospitalization. But he still screams a lot 34 years old (End of February 2022 - end of April 2023) The screaming behavior gradually decreases, but the patient becomes unable to speak, swallow, walk, and relieve himself or herself Family members took the patient to an outside hospital for rehabilitation. Nasal feeding tube for food administration, has been adhering to the use of "lithium carbonate sustained release tablets 0.3-0.6/ day" and other treatment. May 2023 Some recovery in swallowing movements, but still no speech. In September 2023, the patient can slowly eat autonomously, defecate autonomously, and simply communicate with his family. But walking gait is still unstable, easy to fall. By April 2023, speech and life skills had basically returned to their previous state. 36 years old (January 2024) Patients with recurrence of disease, excited multilingual, reduced sleep, energetic, easy to lose temper, throwing things After hospitalization, the patients were treated with "Olanzapine 1.25-5mg/ day, lithium carbonate sustained-release tablets 0.6-0.9/ day", combined with dextrose-potassium chlorine-insulin liquid drip therapy, physical and psychological therapy. About 2 weeks after the patient's mood was significantly relieved, quiet cooperation, sleep improved 36 years old (March 2024) The patient showed stable mood, no disordered behavior, simple speech and good sleep The outpatient treatment was "Olanzapine 5mg/ day, lithium carbonate sustained-release tablet 0.9g/ day" 36 years old (April 2024) The patient had stable mood, no disordered behavior, simple speech and good sleep The outpatient treatment was "Olanzapine 5mg/ day, lithium carbonate sustained-release tablet 0.9g/ day" Discussion This 36-year-old woman had delayed mental development since childhood and multiple manic episodes in early adulthood. In 2022, her life skills regressed for over a year, followed by another manic episode. To review her diagnosis and treatment, we must address three questions: What was her diagnosis? What treatment should she receive? How can we better screen similar patients for early intervention? This patient had whole-exome sequencing in April 2022, revealing a SHANK3 gene variant c.3865dup (a loss-of-function frameshift mutation). She had speech, motor, and social developmental disorders since childhood and significant psychiatric issues from age 18, including mood swings, irritability, and erratic behavior. Her symptoms align with PMS-related psychiatric features. Studies show that about 54% of PMS patients with psychiatric symptoms may meet the criteria for bipolar disorder. They often display frequent screaming, sudden bursts of activity, or an inability to stay still due to intellectual disabilities [7] . Previous studies on PMS with comorbid mental disorders have mostly been case reports. A study of 38 adolescents and adults with PMS found common psychiatric symptoms like emotional instability, catatonia, and significant skill loss, often triggered by infections, hormonal changes, or stress [4] . A recent review found that various studies have diagnosed bipolar disorder in PMS patients, observing symptoms such as behavioral instability, mood cycling, irritability, aggression, screaming, disinhibition, hypersexuality, and sleep disturbances，Neuropsychiatric symptoms are common in PMS patients. It appears in adolescence or early adulthood. [3] . While there's a possible link between PMS and bipolar disorder, more research is needed to understand their unique symptoms [8] . Intellectual disability can obscure bipolar symptoms, complicating diagnosis and treatment. Detailed assessments using multiple tools and methods, including clinical observation and patient history, are recommended. PMS can cause neurological and psychiatric deterioration affecting cognition, speech, motor, and daily living skills, often with speech regression first. The study on PMS patients shows that 43% of the patients experienced regression [9] .This is a recognized characteristic of PMS. Triggers can be biological (fever, infection, hormones, and malignant syndromes) or environmental [10] . In early 2022, this patient experienced a decline in speech and daily living skills following antipsychotic treatment and a lung infection, but improved over the year. By early 2023, the patient's speech and behavioral abilities returned to normal, allowing her to communicate, eat, use the restroom, and walk outside. PMS regression can happen at any age, often starting in middle childhood and impacting cognition, speech, motor skills, and daily living [9] . Persistent issues may be due to SHANK3 gene haploinsufficiency, affecting recovery from psychiatric and physical events [11] . About half partially recovered some social functions within three years, though psychiatric issues persisted [12] . PMS management guidelines recommend mood stabilizers and atypical antipsychotics for mood disorders. Mood stabilizers alone or with antipsychotics can stabilize mood and behavior in bipolar disorder, while antipsychotic monotherapy is less effective and poorly tolerated [6] . There is also a case report that lithium salt reversed the degenerative symptoms and stabilized the patient's behavior. Two patients respectively took 1.5g/d and 1.0g/d of lithium salt. Two years later, one of the patients even recovered to the level before the degeneration occurred. [13] . Other PMS patients with emotional instability, hyperactivity, and sleep issues improved on lithium 0.4g/day and 0.7g/day, lithium is reported to reverse regression symptoms [14, 15] . In 2022, our patient experienced neuroleptic malignant syndrome (NMS) during antipsychotic medication changes. Treatment involved discontinuing olanzapine, hydration, and modified electroconvulsive therapy (MECT), stabilizing the mood and clearing consciousness. Lithium sustained-release tablets were added later during rehabilitation. During the 2024 hospitalization, the patient received olanzapine1.25-5 mg/day + lithium sustained-release tablets 0.3-0.9 g/day using a cautious incremental dosing strategy to minimize extrapyramidal side effects. Preventing infections is crucial for PMS patients, as infections can trigger regression. Behavioral interventions are the primary treatment for aggression, repetitive actions, and self-injurious behavior, using Applied Behavior Analysis principles for reinforced behavioral plans when necessary [16] .Patients with regression experience significant life skill deterioration, often requiring long-term rehabilitation and regular nasogastric tube care from community hospitals. Comprehensive management helps maintain their quality of life, providing ongoing medical support and supervision during rehabilitation. Conclusion PMS is a rare neurodevelopmental syndrome, and some studies suggest atypical bipolar disorder may be part of its psychopathological profile. Clinically, if a patient has intellectual disability and autism-like behaviors in childhood, and later shows hyperexcited screaming, irritability, destructive behavior, reduced sleep, and high energy during adolescence and early adulthood, along with speech and daily function regression indicating atypical bipolar disorder, PMS should be considered. Detailed history and genetic testing are needed to avoid misdiagnosis and mistreatment. Long-term rehabilitation and regular nasogastric tube care from community hospitals may be necessary to maintain patients' quality of life and provide ongoing medical support. Declarations Funding The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Zhejiang Province Medicine and Health Science and Technology Program (No.2023KY980); Hangzhou Municipal Health and Family Planning Commission. (No.A20220133) Data availability Not applicable as this is a case report. Author's contribution YS. XL and PG.YX wrote the main manuscript text and QZ.WC prepared tables 1-2. All authors reviewed the manuscript. Acknowledgments. We thank NZ and all the medical staff who provided care to the patient. Ethics approval and consent to participate This study was approved by the Ethics Committee of the Hangzhou Seventh People's Hospital (019 (2022)). Consent for publication Written informed consent was obtained from the patient and his legally authorized representative for the publication of this case report in accordance with the journal’s patient consent policy. Competing interest The authors declare that there is no conflict of interest regarding the publication of this article. References Cammarata-Scalisi F, Callea M, Martinelli D, et al. Clinical and Genetic Aspects of Phelan-McDermid Syndrome: An Interdisciplinary Approach to Management. Genes (Basel). 2022. 13(3): 504. Bonaglia MC, Giorda R, Beri S, et al. Molecular mechanisms generating and stabilizing terminal 22q13 deletions in 44 subjects with Phelan/McDermid syndrome. PLoS Genet. 2011. 7(7): e1002173. Kolevzon A, Delaby E, Berry-Kravis E, Buxbaum JD, Betancur C. Neuropsychiatric decompensation in adolescents and adults with Phelan-McDermid syndrome: a systematic review of the literature. Mol Autism. 2019. 10: 50. Kohlenberg TM, Trelles MP, McLarney B, Betancur C, Thurm A, Kolevzon A. Psychiatric illness and regression in individuals with Phelan-McDermid syndrome. J Neurodev Disord. 2020. 12(1): 7. Frank Y. The Neurological Manifestations of Phelan-McDermid Syndrome. Pediatr Neurol. 2021. 122: 59-64. Dhossche DM, Wachtel LE. Catatonia is hidden in plain sight among different pediatric disorders: a review article. Pediatr Neurol. 2010. 43(5): 307-15. Denayer A, Van Esch H, de Ravel T, et al. Neuropsychopathology in 7 Patients with the 22q13 Deletion Syndrome: Presence of Bipolar Disorder and Progressive Loss of Skills. Mol Syndromol. 2012. 3(1): 14-20. Jungová P, Čumová A, Kramarová V, et al. Phelan-McDermid syndrome in adult patient with atypical bipolar psychosis repeatedly triggered by febrility. Neurocase. 2018. 24(4): 227-230. Reierson G, Bernstein J, Froehlich-Santino W, et al. Characterizing regression in Phelan McDermid Syndrome (22q13 deletion syndrome). J Psychiatr Res. 2017. 91: 139-144. Egger JI, Zwanenburg RJ, van Ravenswaaij-Arts CM, Kleefstra T, Verhoeven WM. Neuropsychological phenotype and psychopathology in seven adult patients with Phelan-McDermid syndrome: implications for treatment strategy. Genes Brain Behav. 2016. 15(4): 395-404. De Rubeis S, Siper PM, Durkin A, et al. Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations. Mol Autism. 2018. 9: 31. Burdeus-Olavarrieta M, San José-Cáceres A, García-Alcón A, González-Peñas J, Hernández-Jusdado P, Parellada-Redondo M. Characterisation of the clinical phenotype in Phelan-McDermid syndrome. J Neurodev Disord. 2021. 13(1): 26. Serret S, Thümmler S, Dor E, Vesperini S, Santos A, Askenazy F. Lithium as a rescue therapy for regression and catatonia features in two SHANK3 patients with autism spectrum disorder: case reports. BMC Psychiatry. 2015. 15: 107. Egger J, Verhoeven W, Groenendijk-Reijenga R, Kant SG. Phelan-McDermid syndrome due to SHANK3 mutation in an intellectually disabled adult male: successful treatment with lithium. BMJ Case Rep. 2017. 2017: bcr2017220778. van Balkom I, Burdeus-Olavarrieta M, Cooke J, et al. Consensus recommendations on mental health issues in Phelan-McDermid syndrome. Eur J Med Genet. 2023. 66(6): 104770. Wang X, McCoy PA, Rodriguiz RM, et al. Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum Mol Genet. 2011. 20(15): 3093-108. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4611416","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":320244282,"identity":"1678f1a0-73bd-407c-a6d6-9e0897305e8f","order_by":0,"name":"Yuyong Sun","email":"","orcid":"","institution":"Affiliated Mental Health Center \u0026 Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuyong","middleName":"","lastName":"Sun","suffix":""},{"id":320244283,"identity":"c3e53a19-ec49-417c-8622-e6b2472a6da3","order_by":1,"name":"Yong Xia","email":"","orcid":"","institution":"Affiliated Mental Health Center \u0026 Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yong","middleName":"","lastName":"Xia","suffix":""},{"id":320244284,"identity":"ba57357f-993d-4736-9fa5-179f9aba7929","order_by":2,"name":"Qianna Zhi","email":"","orcid":"","institution":"Affiliated Mental Health Center \u0026 Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Qianna","middleName":"","lastName":"Zhi","suffix":""},{"id":320244285,"identity":"58bbada9-1a38-46e1-ad74-3131a39d7107","order_by":3,"name":"Pengfei Guo","email":"","orcid":"","institution":"Affiliated Mental Health Center \u0026 Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Pengfei","middleName":"","lastName":"Guo","suffix":""},{"id":320244286,"identity":"7fa86883-6123-40bc-81bf-77c74e39213d","order_by":4,"name":"Wenjing Cui","email":"","orcid":"","institution":"Affiliated Mental Health Center \u0026 Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Wenjing","middleName":"","lastName":"Cui","suffix":""},{"id":320244287,"identity":"9e3c554e-e0b1-4fe9-9ade-755dbc582865","order_by":5,"name":"Xiaoyan Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYBACPmYgkQBmMjY++GBgw8PP3oBfCxtCC3Oz4YyKNBnJngMEtCCY7G3SPGcO2xjccCCghZ3HTOJBjU1i/+zGNmnetvM8DDcYGD98zMHnMB5jg4RjaYkz7hxstpzbdpuHcXYDs+TMbXi1GD5IYDuc2HAjsfHGW6AWZpkDbMy8+LUYHEj4dzhx/o3EBgnetnM8bBIJBLUYPkhsO5y44UZikyTPmQM8PIS1sBUbJPalGW+8kQgK5GQeCZ6DzXj9ws9/eJvkj282svNupD8ERqWdvf3x5oMfPuLRAgOODQg2YwMuVSjAnihVo2AUjIJRMDIBACTgUrYSArUxAAAAAElFTkSuQmCC","orcid":"","institution":"Affiliated Mental Health Center \u0026 Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Xiaoyan","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2024-06-20 11:26:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4611416/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4611416/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60599514,"identity":"635d83d5-d15b-4359-a569-e9fe1af92ad1","added_by":"auto","created_at":"2024-07-18 15:58:22","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":396900,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIGV diagram of SHANK3 gene variant c.3865dup sequencing results of the subject\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1111111.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4611416/v1/e170a6d55a05a9745efb0cda.jpg"},{"id":60933158,"identity":"31b1f841-dd3d-4390-a692-5c4aaff5fba9","added_by":"auto","created_at":"2024-07-23 17:48:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":780885,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4611416/v1/94c8f2d3-b30b-426e-953d-4280da10b093.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Case report: Bipolar disorder in Phelan-McDermid syndrome","fulltext":[{"header":"Background","content":"\u003cp\u003ePhelan-McDermid syndrome (PMS), also known as 22q13.3 deletion syndrome, is a rare neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene on chromosome 22\u003csup\u003e[1]\u003c/sup\u003e. Genetic variations in PMS include terminal or interstitial deletions, translocations, mutations, or ring chromosomes\u003csup\u003e[2]\u003c/sup\u003e. This syndrome is characterized by intellectual disabilities, delayed language development, autism spectrum disorders, and motor tone abnormalities\u003csup\u003e[3]\u003c/sup\u003e. SHANK3 gene abnormalities increase the risk of mental disorders\u003csup\u003e[4]\u003c/sup\u003e. Studies indicate that infections, hormonal changes, and life stress can trigger psychiatric symptoms in PMS patients, with psychiatric disorders typically appearing during adolescence or early adulthood\u003csup\u003e[5]\u003c/sup\u003e. Approximately 54% of PMS patients may meet the criteria for bipolar disorder, and about half may experience behavioral regression\u003csup\u003e[3]\u003c/sup\u003e.We report a 36-year-old female PMS patient with delayed mental development from childhood and recurrent manic episodes from age 18. Her treatment was complicated by severe reactions, including neuroleptic malignant syndrome, leading to regression in speech and daily living skills. After a year of treatment, some improvement was noted, but manic symptoms recurred, necessitating further treatment.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eThe patient is a 36-year-old female. Her family reported that she could only point at objects and make sounds at the age of 2, called her mother at age 3, and began walking at that time. In early childhood, she was often silent, seldom speaking, and had no active social interactions with those around her. When she started elementary school, her academic performance was poor; she could not perform addition and subtraction within 100 and could not leave the house alone. Her daily life required family assistance. The family did not take her to the hospital for an examination, and due to her inability to cope with studies, she dropped out after the sixth grade. Living under the family\u0026apos;s care, she could dress herself, eat, and follow simple instructions. At age 18, she first exhibited noticeable emotional instability: she became talkative, spoke grandiosely, \u0026nbsp;she was excessively excited and screamed frequently, sleeping only 2-3 hours per day yet appeared very energetic, and demanded her family to buy many things for her. These episodes recurred several times, each lasting about a month, followed by periods of reclusive and sparse speech. In the same year, she was hospitalized for one month, with a Wechsler Intelligence Scale score of 54, diagnosed with \u0026quot;1. Mental retardation with significant behavioral defects requiring attention or treatment; 2. Bipolar disorder, currently in a manic episode without psychotic symptoms.\u0026quot; Treatment included Clozapine and Oxcarbazepine, though the family could not provide specific dosages; she discontinued medication after about six months. When her condition was stable, her mood and behavior were stable, her speech remained simple, and she lived independently with family assistance. At 23 years old, she got married and gave birth to a daughter at 24 years old. After childbirth, her condition relapsed once: she became hyper-excited, talkative, scattered in speech, spent excessively, and demanded that the family buy large amounts of toilet paper. After another hospitalization and two months of treatment, her condition improved, and she continued treatment with Clozapine (25-75 mg/day) until June 2021, when she relapsed again, displaying irritability, excessive talking with simple words, shouting, walking around the house, and sleeplessness at night. In August 2021, she was hospitalized again locally and treated with Lurasidone (40-80 mg/day), Clozapine (25-100 mg/day), Oxcarbazepine (1.2 g/day), and Lorazepam (2 mg/day), but her condition remained poorly controlled, with persistent emotional instability and shouting. By December 2021, she became very sluggish and had a stiff walking posture. Doctors gradually discontinued Clozapine and Lurasidone, switching her to Olanzapine (5-20 mg/day) over two weeks. However, her condition worsened, sleep deteriorated, she screamed continuously at night, her limbs became rigid, she held her hands up, and swallowing became difficult. On January 13, 2022, her condition suddenly worsened: she became rigid, continuously screamed, sweated profusely, her body temperature rose to 38.8\u0026deg;C, blood pressure spiked to 170/110 mmHg, heart rate increased to 100-130 bpm, and she experienced incontinence. Her right hand became claw-like, muscle tone significantly increased, and she was in a state of rigid flexion spasms with a creatine kinase level of 11154 U/L. On January 17, 2022, she was admitted to our hospital. Upon admission, she was unconscious, disoriented, rigid, unable to speak, with tense facial expressions, unable to eat independently, had difficulty swallowing, and continuously screamed \u0026quot;ah, ah.\u0026quot; Detailed lab results are in the attached table 1. She was diagnosed as \u0026quot;1. Neuroleptic malignant syndrome; 2. Mental retardation with significant behavioral defects requiring attention or treatment.\u0026quot; Since she was unconscious and not exhibiting mania, a bipolar disorder diagnosis was not made at this time. During hospitalization, she was unable to eat and was incontinent, so a nasogastric tube and urinary catheter were placed. Olanzapine was gradually discontinued and Diazepam mainline (10 mg/day) was administered to alleviate tension, combined with 10 sessions of MECT (modified electroconvulsive therapy). Lung infection was detected at admission, treated with Cefoperazone-Sulbactam (3.0 g Q12h),\u003c/p\u003e\n\u003cp\u003eadminister fluid rehydration therapy. After the first week, the patient had no fever, her heart rate, blood pressure, but she remained shouting. By the 14th day, she was still unaware and in a state of rigid flexion spasms, we performed a lumbar puncture on the patient, including routine, biochemical, and autoimmune encephalitis panel, all of which were negative. By the 20th day, her lung infection had mostly resolved. On the 24th day, her consciousness began to clear, she responded to a video of her daughter Diazepam was replaced with Lorazepam (2 mg/day). Although she\u0026apos;s a little more emotionally stable, the most severe problems were her inability to perform daily self-care, feed herself, void independently, and the presence of increased muscle tone with sustained rigid flexion spasms. The family \u0026nbsp; \u0026nbsp;members transferred her to a general hospital for continued rehabilitation for an additional five months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 Laboratory examination\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTest time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003etest project name\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003etest result\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eJanuary 17, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBlood routine examination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWBC 4.37\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003cp\u003eRBC 3.91\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHGB 106g/L\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePLT 26710\u003csup\u003e9\u003c/sup\u003e/L\u0026uarr;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eJanuary 17, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eblood biochemistry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eALT 62.5U/L\u0026uarr;\u003c/p\u003e\n \u003cp\u003eAST 136.3U/L\u0026uarr;\u003c/p\u003e\n \u003cp\u003eCK 11154U/L\u0026uarr;\u003c/p\u003e\n \u003cp\u003eCK-MB 218.21U/L\u0026uarr;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eJanuary 18, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBlood gas analysis, female tumor markers, normal thyroid function。\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003enormal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eJanuary 19, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHead MRI: Slight vascular origin white matter high signal may be seen in both lateral ventricles, Fazekas grade 1. EEG: Increase in fast waves.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFebruary 1, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRoutine cerebrospinal fluid examination, cerebrospinal fluid biochemistry, autoimmune encephalitis antibodies.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003enormal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFebruary 12, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBlood routine examination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWBC5.08\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003cp\u003eRBC3.95\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003csup\u003e\u0026nbsp;\u0026nbsp;\u003c/sup\u003eHGB134g/L\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePLT192/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFebruary 12, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eblood biochemistry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eALT 16.3U/L\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAST 19.3U/L\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCK 413U/L\u0026uarr;\u003c/p\u003e\n \u003cp\u003eCK-MB 15.9U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFebruary 21, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBlood routine examination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWBC5.92\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003cp\u003eRBC3.95\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003csup\u003e\u0026nbsp;\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eHGB 124g/L\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePLT 212/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFebruary 21, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eblood biochemistry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eALT 17.1U/L\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAST 22.1U/L\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCK 263U/L\u0026uarr;\u003c/p\u003e\n \u003cp\u003eCK-MB 17.74U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eDuring the patient\u0026apos;s hospitalization at the rehabilitation hospital, considering her developmental delay and recurrent manic episodes, along with a deterioration in life skills and persistent high muscle tone in her limbs, whole-exome sequencing was performed in April 2022, identifying a SHANK3 gene mutation c.3865dup associated with her phenotype，See details in Figure 1. The diagnosis was Phelan-McDermid syndrome. She was treated with Lithium carbonate sustained-release tablets (0.3-0.6g/day) in combination with rehabilitation therapy and was discharged home for continued treatment in July 2022. At discharge, her mood was more stable than before, and she could urinate and defecate independently, allowing the removal of the urinary catheter. However, she still had slow swallowing and required a nasogastric tube, could not speak a complete sentence, occasionally said \u0026quot;daughter\u0026quot; or \u0026quot;mom,\u0026quot; and sometimes screamed \u0026quot;ah ah.\u0026quot; She lay in bed all day, and community healthcare workers regularly visited to care for her nasogastric tube. By November 2022, there was a significant improvement in her condition: her mood gradually stabilized, she could again speak simple words to her family, slowly eat independently, and her nasogastric tube was removed. However, she still had elevated muscle tone, walked unsteadily, and easily fell when walking. Her nutritional status improved, and she gained 20 pounds eleven months after discharge. It took 13 months for her walking instability symptoms to improve significantly. During this period, she continued to receive Lithium carbonate (0.6g/day) treatment and could manage her personal hygiene with family assistance. Her condition remained basically stable. In January 2024, She had a relapse. For about a week, she suddenly became very excited, talked loudly and continuously, yelled, cursed her family, and smashed objects. She often made sexually suggestive remarks, slept only 2-3 hours at night, and was still very energetic during the day, running around the house non-stop. She was admitted to our hospital for the second time in February 2024. The physical examination showed no obvious abnormalities, and she showed signs of manic syndrome. All laboratory tests were normal.The Bech-Rafaelsen Mania Rating Scale (BRMS) score was 26. Based on her complex medical history, psychiatric examination, and lab results, the diagnoses upon this admission were: 1. Intellectual disability with significant behavioral defects requiring attention or treatment; 2. Bipolar disorder, currently manic without psychotic symptoms; 3. Phelan-McDermid syndrome. For treatment, considering her history of multiple manic episodes, the occurrence of neuroleptic malignant syndrome during treatment two years ago, the subsequent deterioration in speech and motor skills, and the difficulty in regaining these skills over nearly 11 months of rehabilitation, we reviewed the literature and held multiple discussions. It was concluded that patients with Phelan-McDermid syndrome are very sensitive to antipsychotics, necessitating low doses\u003csup\u003e[6]\u003c/sup\u003e. In this treatment, we used Olanzapine 1.25-5mg /day + Lithium carbonate sustained-release tablets 0.6-0.9g/day to help stabilize her mood. For severe agitation, temporary intramuscular injections of Eszopiclone 2-4mg were administered. Simultaneously, with pharmacological treatment, we provided psychological counseling and comfort therapy, communicating with the patient 2-3 times daily for about 15 minutes, teaching her repeatedly not to shout or behave aggressively. Her condition significantly improved about two weeks into hospitalization. The day before discharge, her BRMS score was 6. No severe side effects like neuroleptic malignant syndrome occurred during this treatment. Follow-up two months later showed her mood was stable. The medication combination of Olanzapine(5mg/day) and Lithium carbonate sustained-release tablets (0.9g/day)was effective. Detailed diagnosis and treatment processes are documented in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 1 insert here\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e \u003cstrong\u003ePatient disease course diagnosis and treatment timeline table.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e2-3 years old\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003eLate speech development, late walking development, will not actively contact the people around\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.612244897959183%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e8-13 years old\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003eLearning difficulties, poor grades, need family assistance in personal life such as tying shoelaces, sixth grade elementary school suspension due to learning difficulties\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.612244897959183%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e18 years old\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003eFor the first time, there are hyperactive screaming, more words, less sleep, like to buy things, energy and other behaviors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003eMerriam-webster Intelligence score 54\u003c/p\u003e\n \u003cp\u003eInpatient diagnosis: 1, mental retardation, significant behavioral deficits requiring attention or treatment; 2. Bipolar disorder, currently a manic episode without psychotic symptoms, has received \u0026quot;clozapine, oxcarbazepine\u0026quot; and other treatments\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.612244897959183%\" valign=\"top\"\u003e\n \u003cp\u003eImproved after treatment, normal mood stable. But repeated manic episodes. Usually, personal life and speech are simple, and personal life needs the assistance of family members\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e23 years old\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003eget married\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.612244897959183%\" valign=\"top\"\u003e\n \u003cp\u003eemotionormal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e24 years old\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003eGive birth to a daughter, postpartum 1 month when the disease attack 1 time, hyper language, spend more money, buy a lot of toilet paper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003eHe was treated with clozapine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.612244897959183%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 2 months, the patient\u0026apos;s mood gradually stabilized, and long-term treatment with clozapine tablets 25-75mg/day.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e33 years old\u003c/p\u003e\n \u003cp\u003e(June 2021)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with recurrent disease, hyperactivity, excessive speech, screaming, sleep loss, high energy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003eHospitalized for treatment of \u0026quot;Lurasidone 40-80mg/ day, clozapine tablet 25-100mg/ day, oxazepine 1.2/ day, Lorazepam 2mg/ day\u0026quot;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.612244897959183%\" valign=\"top\"\u003e\n \u003cp\u003eThe patient\u0026apos;s condition did not improve well, emotional excitement, frequent high-pitched screaming\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e33 years old\u003c/p\u003e\n \u003cp\u003e(December 2021)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003eThe patient\u0026apos;s movements become sluggish and postural behavior becomes rigid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003eDoctors stop \u0026quot;clozapine lurasidone\u0026quot; and replace it with \u0026quot;Olanzapine 5-20mg/ day\u0026quot; within 2 weeks.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.612244897959183%\" valign=\"top\"\u003e\n \u003cp\u003eSleep becomes worse, stiffness becomes more severe, and swallowing becomes difficult\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e34 years old\u003c/p\u003e\n \u003cp\u003e(January 2022)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003eThe patient\u0026apos;s body rigidity was more obvious, the body temperature was 38.8℃, sweating, increased blood pressure, increased heart rate, urinary and bowel incontinence, body rigidity and distortion, and the right hand was rigid and bent like chicken feet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.612244897959183%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e34 years old\u003c/p\u003e\n \u003cp\u003e(January 17, 2022)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003eThe patient has confusion, disorientation, rigidity, difficulty swallowing, and occasional screaming\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003eThe patient came to our hospital for emergency treatment. After hospitalization, the treatment of olanzapine was discontinued, fluid replenishing support, diazepam needle 10mg/ day intravenous drip treatment, combined with MECT treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.612244897959183%\" valign=\"top\"\u003e\n \u003cp\u003eThe symptoms of fever and sweating were relieved after 1 week of hospitalization, and the symptoms of tension and rigidity were relieved after 2 weeks of hospitalization. But he still screams a lot\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e34 years old\u003c/p\u003e\n \u003cp\u003e(End of February 2022 - end of April 2023)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003eThe screaming behavior gradually decreases, but the patient becomes unable to speak, swallow, walk, and relieve himself or herself\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003eFamily members took the patient to an outside hospital for rehabilitation. Nasal feeding tube for food administration, has been adhering to the use of \u0026quot;lithium carbonate sustained release tablets 0.3-0.6/ day\u0026quot; and other treatment.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.612244897959183%\" valign=\"top\"\u003e\n \u003cp\u003eMay 2023 Some recovery in swallowing movements, but still no speech. In September 2023, the patient can slowly eat autonomously, defecate autonomously, and simply communicate with his family. But walking gait is still unstable, easy to fall. By April 2023, speech and life skills had basically returned to their previous state.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e36 years old\u003c/p\u003e\n \u003cp\u003e(January 2024)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with recurrence of disease, excited multilingual, reduced sleep, energetic, easy to lose temper, throwing things\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003eAfter hospitalization, the patients were treated with \u0026quot;Olanzapine 1.25-5mg/ day, lithium carbonate sustained-release tablets 0.6-0.9/ day\u0026quot;, combined with dextrose-potassium chlorine-insulin liquid drip therapy, physical and psychological therapy.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.612244897959183%\" valign=\"top\"\u003e\n \u003cp\u003eAbout 2 weeks after the patient\u0026apos;s mood was significantly relieved, quiet cooperation, sleep improved\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e36 years old\u003c/p\u003e\n \u003cp\u003e(March 2024)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003eThe patient showed stable mood, no disordered behavior, simple speech and good sleep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003eThe outpatient treatment was \u0026quot;Olanzapine 5mg/ day, lithium carbonate sustained-release tablet 0.9g/ day\u0026quot;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.612244897959183%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.306122448979592%\" valign=\"top\"\u003e\n \u003cp\u003e36 years old\u003c/p\u003e\n \u003cp\u003e(April 2024)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.53061224489796%\" valign=\"top\"\u003e\n \u003cp\u003eThe patient had stable mood, no disordered behavior, simple speech and good sleep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.551020408163264%\" valign=\"top\"\u003e\n \u003cp\u003eThe outpatient treatment was \u0026quot;Olanzapine 5mg/ day, lithium carbonate sustained-release tablet 0.9g/ day\u0026quot;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.612244897959183%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis 36-year-old woman had delayed mental development since childhood and multiple manic episodes in early adulthood. In 2022, her life skills regressed for over a year, followed by another manic episode. To review her diagnosis and treatment, we must address three questions: What was her diagnosis? What treatment should she receive? How can we better screen similar patients for early intervention?\u003c/p\u003e\n\u003cp\u003eThis patient had whole-exome sequencing in April 2022, revealing a SHANK3 gene variant c.3865dup (a loss-of-function frameshift mutation). She had speech, motor, and social developmental disorders since childhood and significant psychiatric issues from age 18, including mood swings, irritability, and erratic behavior. Her symptoms align with PMS-related psychiatric features. Studies show that about 54% of PMS patients with psychiatric symptoms may meet the criteria for bipolar disorder. They often display frequent screaming, sudden bursts of activity, or an inability to stay still due to intellectual disabilities\u003csup\u003e[7]\u003c/sup\u003e.\u0026nbsp;Previous studies on PMS with comorbid mental disorders have mostly been case reports. A study of 38 adolescents and adults with PMS found common psychiatric symptoms like emotional instability, catatonia, and significant skill loss, often triggered by infections, hormonal changes, or stress\u003csup\u003e[4]\u003c/sup\u003e. A recent review found that various studies have diagnosed bipolar disorder in PMS patients, observing symptoms such as behavioral instability, mood cycling, irritability, aggression, screaming, disinhibition, hypersexuality, and sleep disturbances，Neuropsychiatric symptoms are common in PMS patients. It appears in adolescence or early adulthood.\u003csup\u003e[3]\u003c/sup\u003e. While there\u0026apos;s a possible link between PMS and bipolar disorder, more research is needed to understand their unique symptoms\u003csup\u003e[8]\u003c/sup\u003e. Intellectual disability can obscure bipolar symptoms, complicating diagnosis and treatment. Detailed assessments using multiple tools and methods, including clinical observation and patient history, are recommended.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePMS can cause neurological and psychiatric deterioration affecting cognition, speech, motor, and daily living skills, often with speech regression first. The study on PMS patients shows that 43% of the patients experienced regression\u0026nbsp;\u003csup\u003e[9]\u003c/sup\u003e.This is a recognized characteristic of PMS. Triggers can be biological (fever, infection, hormones, and malignant syndromes) or environmental\u003csup\u003e[10]\u003c/sup\u003e.\u0026nbsp;In early 2022, this patient experienced a decline in speech and daily living skills following antipsychotic treatment and a lung infection, but improved over the year. By early 2023, the patient\u0026apos;s speech and behavioral abilities returned to normal, allowing her to communicate, eat, use the restroom, and walk outside. PMS regression can happen at any age, often starting in middle childhood and impacting cognition, speech, motor skills, and daily living\u003csup\u003e[9]\u003c/sup\u003e. Persistent issues may be due to SHANK3 gene haploinsufficiency, affecting recovery from psychiatric and physical events\u003csup\u003e[11]\u003c/sup\u003e. About half partially recovered some social functions within three years, though psychiatric issues persisted\u003csup\u003e[12]\u003c/sup\u003e. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePMS management guidelines recommend mood stabilizers and atypical antipsychotics for mood disorders. Mood stabilizers alone or with antipsychotics can stabilize mood and behavior in bipolar disorder, while antipsychotic monotherapy is less effective and poorly tolerated\u003csup\u003e[6]\u003c/sup\u003e. There is also a case report that lithium salt reversed the degenerative symptoms and stabilized the patient\u0026apos;s behavior. Two patients respectively took 1.5g/d and 1.0g/d of lithium salt. Two years later, one of the patients even recovered to the level before the degeneration occurred.\u0026nbsp;\u003csup\u003e[13]\u003c/sup\u003e. Other PMS patients with emotional instability, hyperactivity, and sleep issues improved on lithium 0.4g/day and 0.7g/day, lithium is reported to reverse regression symptoms\u003csup\u003e[14, 15]\u003c/sup\u003e. In 2022, our patient experienced neuroleptic malignant syndrome (NMS) during antipsychotic medication changes. Treatment involved discontinuing olanzapine, hydration, and modified electroconvulsive therapy (MECT), stabilizing the mood and clearing consciousness. Lithium sustained-release tablets were added later during rehabilitation. During the 2024 hospitalization, the patient received olanzapine1.25-5 mg/day + lithium sustained-release tablets 0.3-0.9 g/day using a cautious incremental dosing strategy to minimize extrapyramidal side effects. Preventing infections is crucial for PMS patients, as infections can trigger regression. Behavioral interventions are the primary treatment for aggression, repetitive actions, and self-injurious behavior, using Applied Behavior Analysis \u0026nbsp;principles for reinforced behavioral plans when necessary\u003csup\u003e[16]\u003c/sup\u003e.Patients with regression experience significant life skill deterioration, often requiring long-term rehabilitation and regular nasogastric tube care from community hospitals. Comprehensive management helps maintain their quality of life, providing ongoing medical support and supervision during rehabilitation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePMS is a rare neurodevelopmental syndrome, and some studies suggest atypical bipolar disorder may be part of its psychopathological profile. Clinically, if a patient has intellectual disability and autism-like behaviors in childhood, and later shows hyperexcited screaming, irritability, destructive behavior, reduced sleep, and high energy during adolescence and early adulthood, along with speech and daily function regression indicating atypical bipolar disorder, PMS should be considered. Detailed history and genetic testing are needed to avoid misdiagnosis and mistreatment. Long-term rehabilitation and regular nasogastric tube care from community hospitals may be necessary to maintain patients\u0026apos; quality of life and provide ongoing medical support.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) declare\u0026nbsp;financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Zhejiang Province Medicine and Health Science and Technology Program (No.2023KY980); Hangzhou Municipal Health and Family Planning Commission. (No.A20220133)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable as this is a case report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026apos;s contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYS. XL and PG.YX wrote the main manuscript text and QZ.WC prepared tables 1-2. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank NZ and all the medical staff who provided care to the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the Hangzhou Seventh People\u0026apos;s Hospital (019 (2022)).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient and his legally authorized representative for the publication of this case report in accordance with the journal\u0026rsquo;s patient consent policy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest regarding the publication of this article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCammarata-Scalisi F, Callea M, Martinelli D, et al. 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Pediatr Neurol. 2021. 122: 59-64.\u003c/li\u003e\n\u003cli\u003eDhossche DM, Wachtel LE. Catatonia is hidden in plain sight among different pediatric disorders: a review article. Pediatr Neurol. 2010. 43(5): 307-15.\u003c/li\u003e\n\u003cli\u003eDenayer A, Van Esch H, de Ravel T, et al. Neuropsychopathology in 7 Patients with the 22q13 Deletion Syndrome: Presence of Bipolar Disorder and Progressive Loss of Skills. Mol Syndromol. 2012. 3(1): 14-20.\u003c/li\u003e\n\u003cli\u003eJungov\u0026aacute; P, Čumov\u0026aacute; A, Kramarov\u0026aacute; V, et al. Phelan-McDermid syndrome in adult patient with atypical bipolar psychosis repeatedly triggered by febrility. Neurocase. 2018. 24(4): 227-230.\u003c/li\u003e\n\u003cli\u003eReierson G, Bernstein J, Froehlich-Santino W, et al. Characterizing regression in Phelan McDermid Syndrome (22q13 deletion syndrome). J Psychiatr Res. 2017. 91: 139-144.\u003c/li\u003e\n\u003cli\u003eEgger JI, Zwanenburg RJ, van Ravenswaaij-Arts CM, Kleefstra T, Verhoeven WM. Neuropsychological phenotype and psychopathology in seven adult patients with Phelan-McDermid syndrome: implications for treatment strategy. Genes Brain Behav. 2016. 15(4): 395-404.\u003c/li\u003e\n\u003cli\u003eDe Rubeis S, Siper PM, Durkin A, et al. Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations. Mol Autism. 2018. 9: 31.\u003c/li\u003e\n\u003cli\u003eBurdeus-Olavarrieta M, San Jos\u0026eacute;-C\u0026aacute;ceres A, Garc\u0026iacute;a-Alc\u0026oacute;n A, Gonz\u0026aacute;lez-Pe\u0026ntilde;as J, Hern\u0026aacute;ndez-Jusdado P, Parellada-Redondo M. Characterisation of the clinical phenotype in Phelan-McDermid syndrome. J Neurodev Disord. 2021. 13(1): 26.\u003c/li\u003e\n\u003cli\u003eSerret S, Th\u0026uuml;mmler S, Dor E, Vesperini S, Santos A, Askenazy F. Lithium as a rescue therapy for regression and catatonia features in two SHANK3 patients with autism spectrum disorder: case reports. BMC Psychiatry. 2015. 15: 107.\u003c/li\u003e\n\u003cli\u003eEgger J, Verhoeven W, Groenendijk-Reijenga R, Kant SG. Phelan-McDermid syndrome due to SHANK3 mutation in an intellectually disabled adult male: successful treatment with lithium. BMJ Case Rep. 2017. 2017: bcr2017220778.\u003c/li\u003e\n\u003cli\u003evan Balkom I, Burdeus-Olavarrieta M, Cooke J, et al. Consensus recommendations on mental health issues in Phelan-McDermid syndrome. Eur J Med Genet. 2023. 66(6): 104770.\u003c/li\u003e\n\u003cli\u003eWang X, McCoy PA, Rodriguiz RM, et al. Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum Mol Genet. 2011. 20(15): 3093-108.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Phelan-McDermid syndrome, Bipolar disorder, diagnosis, Treatment, Malignant syndrome","lastPublishedDoi":"10.21203/rs.3.rs-4611416/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4611416/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003ePhelan-McDermid syndrome (PMS) is a rare genetic disorder. It involves intellectual disability, delayed language, autism spectrum disorders, motor tone abnormalities, and a high risk of psychiatric symptoms like bipolar disorder.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation \u003c/strong\u003eWe present an 18-year case of a 36-year-old woman with PMS, exhibiting intellectual disabilities, social withdrawal, and stereotyped behavior. Diagnosed with bipolar disorder at 18, she faced treatment challenges, including severe reactions to antipsychotics in 2022, leading to speech and functional regression. Subsequent rehabilitation and comprehensive therapy improved her condition. By 2024, following additional treatment, her symptoms stabilized.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions \u003c/strong\u003ePMS requires detailed history, genetic testing, and long-term supportive care for effective management.\u003c/p\u003e","manuscriptTitle":"Case report: Bipolar disorder in Phelan-McDermid syndrome","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-18 15:58:17","doi":"10.21203/rs.3.rs-4611416/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"964d589b-4b65-462b-bd1c-9f01ef6eb9a9","owner":[],"postedDate":"July 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-23T17:40:11+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-18 15:58:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4611416","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4611416","identity":"rs-4611416","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}