Cervical Dystonia as the Initial Symptom of IRF2BPL-related Disorder: A Case Report

Cervical Dystonia as the Initial Symptom of IRF2BPL-related Disorder: A Case Report | 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 Cervical Dystonia as the Initial Symptom of IRF2BPL-related Disorder: A Case Report Yang Li, ZhiMeng Wan, Xinhua Wan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7319210/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 IRF2BPL -related disorder ,also known as neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, NEDAMSS, is a rare neurogenetic disorder. It typically presents with developmental delay or seizures as the initial symptoms. This report describes a case of IRF2BPL mutation with cervical dystonia as the initial symptom and further explores the treatment strategies for movement symptoms. Case Presentation: A 17-year-old female presented with involuntary leftward head rotation and mild lower limb tremors three years ago. She was diagnosed with cervical dystonia, and after receiving botulinum toxin injections, her symptoms completely resolved. In the following three years, the patient developed worsening lower limb tremors, diagnosed as myoclonic seizures based on EEG findings, along with dysarthria and ataxia. Whole-exome sequencing confirmed the IRF2BPL mutation, and the final diagnosis was IRF2BPL -related syndrome. The patient was treated with carbamazepine, which alleviated the tremor symptoms. Conclusion The treatment of IRF2BPL -related disorder primarily focuses on seizure control, while movement symptoms, such as dystonia, significantly affect the patient's quality of life but are often overlooked. In this case, botulinum toxin effectively controlled the patient's dystonia, providing a new approach to treating movement symptoms. IRF2BPL NEDAMSS dystonia neurodegeneration botulinum Figures Figure 1 Figure 2 Figure 3 Introduction The IRF2BPL gene is located on chromosome 14q24.3, encoding the interferon regulatory factor 2 binding protein (IRF2BPL). While the exact biological function of this gene is not fully understood, it plays an essential role in neuronal development and maintenance 1 . Mutations in IRF2BPL can lead to IRF2BPL -related disorder, also known as neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures (NEDAMSS). This is a rare neurogenetic disorder, with fewer than 70 cases reported 2,3 . The main symptoms of NEDAMSS include developmental delay and seizures, with movement symptoms as the initial presentation being rare. Although movement symptoms (such as dystonia) are common in IRF2BPL -related disorder, there are relatively few reports on its clinical features and treatment, especially the impact of dystonia on the patient's quality of life. This case presents a patient with cervical dystonia as the initial symptom and explores the potential of botulinum toxin treatment in managing movement symptoms, offering new insights into treating this condition. Case summary The patient is a 17-year-old female who developed involuntary leftward head rotation and mild lower limb tremors at the age of 14.The head rotation was approximately 75°, accompanied by tremor and sensory tricks. However, the lower limb symptoms were not initially noted. She was diagnosed with cervical dystonia and treated with botulinum toxin injections, which led to complete resolution of her symptoms. Over the following three years, the patient developed dysarthria, which progressively worsened. At age 17, the lower limb tremors became more pronounced, occurring several times a day with multiple falls during standing and walking. Upper limb tremors began to appear, and fine motor tasks such as writing were affected. There was no loss of consciousness during the episodes, and symptoms were more prominent during emotional stress. However, the cervical dystonia symptoms did not relapse. The patient had normal growth and development during childhood. Her grandfather passed away from motor neuron disease at the age of 49. Neurological examination revealed myoclonus in the limbs, and cognitive assessment showed mild cognitive impairment (MMSE score of 26). Brain MRIs at the ages of 14 and 17 were unremarkable (Fig. 1 ). EEG at both ages revealed generalized high-amplitude slow waves and polyspike-slow waves (Fig. 2 ), leading to the diagnosis of myoclonic epilepsy. Whole-exome sequencing revealed a novel mutation in the IRF2BPL gene (NM_024496), *c.499C > T (p.Gln167*)(Fig. 3 ), which introduces a premature stop codon, resulting in a truncated protein. This mutation was not found in the patient’s parents. Based on the clinical presentation and genetic findings, the diagnosis of IRF2BPL -related disorder was confirmed. The patient was treated with carbamazepine (half tablet, once a day), which led to mild alleviation of myoclonic seizures, though the dysarthria did not significantly improve. Discussion We report a case of IRF2BPL -related disorder with cervical dystonia as the initial symptom. The patient initially presented with cervical dystonia, which was completely resolved with botulinum toxin injection. To date, there have been no reports on botulinum toxin for the treatment of dystonia associated with IRF2BPL -related disorder. A literature search reveals 66 reported cases of IRF2BPL -related disorder (Supplementary Table 1). The onset symptoms in these patients varied widely, including developmental abnormalities (18 cases) and various forms of seizures (such as myoclonic seizures, tonic seizures, infantile spasms, etc., 10 cases). Among these cases, only one patients had generalized dystonia at onset, 4 , and another with lower limb dystonia 5 . Therefore, accurate diagnosis is challenging in the early stages of this disease. We report that in this case, the patient's lower limb symptoms were initially overlooked, and the diagnosis focused solely on the prominent cervical dystonia. This case highlights the importance of considering other signs when dystonia is prominent in the early stages, to avoid misdiagnosis. Although movement symptoms are uncommon in the early stages of the disease, most patients (43/67) will gradually develop one or more movement disorder symptoms as the disease progresses. These symptoms include ataxia (28/43), speech delay or dysarthria (27/43), dystonia (20/43), difficulty walking or unstable gait (18/43), dysphagia (12/43), hypotonia (6/43), chorea (3/43), dance-like movements (2/43), postural instability (2/43), and tremor (1/43). These movement symptoms significantly affect the patients' quality of life. However, due to the severity of seizures and developmental delay, the urgency of treating movement symptoms is often overlooked. Treatment of IRF2BP L-related disorder has primarily focused on seizure control 6,7 . with limited attention to movement symptoms. Few cases have attempted treatment with baclofen, clonazepam, and levodopa, but the effectiveness of these treatments has been poorly reported, with limited success in alleviating movement symptoms. 8–10 In contrast, botulinum toxin injection offers a novel treatment option for IRF2BP L-related disorder associated with dystonia. Botulinum toxin works by inhibiting the signaling between nerves and muscles, effectively reducing muscle hypertonia, especially in cervical dystonia and other types of dystonia. This treatment method has provided the patient with three years of symptom relief without relapse, indicating its strong therapeutic effect on IRF2BPL -related movement symptoms. In this case, genetic testing revealed a novel mutation in the IRF2BPL gene (c.499C > T, p.Gln167*), leading to a premature stop codon and a truncated protein. This mutation has not been previously reported, thus expanding the genetic variation spectrum of IRF2BPL-related syndrome and providing new insights into the genetic mechanisms of the disease. The IRF2BPL gene plays a crucial role in neuronal development and maintenance, and this mutation may lead to the loss of protein function, affecting normal neurodevelopment and function. Conclusion Botulinum toxin injection is a feasible therapy for IRF2BP L-related disorder patients who develop dystonia. Additionally, when diagnosing these patients, other signs should be carefully considered to avoid misdiagnosis due to the prominence of dystonia, ensuring early and accurate diagnosis and timely intervention. Abbreviations NEDAMSS: neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizure s IRF2BPL: interferon regulatory factor 2 binding protein EEG: electroencephalogram MMSE: mini-mental state examination MRI: magnetic resonance imaging Declarations Data availability The raw sequencing data generated during the current study are available in the Genome Sequence Archive for Human (GSA-Human) under accession number HRA019750. Acknowledgements Not applicable. Funding This study was supported by National High Level Hospital Clinical Research Funding(2022-PUMCH-B-018). Author information Authors and Affiliations Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, China 100730 Contributions YL: analysis and interpretation of data, manuscript writing and literature search; ZMW : patient follow-up examination; XHW: reviewed and substantively revised the paper Corresponding author Correspondence to XinHua Wan Ethics declarations Ethics approval and consent to participate The study participants were reviewed and approved by the Medical Review Ethics Committee of the Peking Union Medical College Hospital (reference number: I-24PJ0207). All participants provided written informed consent. Consent for publication Written informed consent for publication of clinical details was obtained from the patient’s parents (legal guardians). Competing interests The authors declare no competing interests. References Sinha Ray, S. et al. Mechanisms of IRF2BPL-related disorders and identification of a potential therapeutic strategy. Cell Rep 41 , 111751 (2022). https://doi.org:10.1016/j.celrep.2022.111751 Vanagunas, T., Ulm Seiwert, E., Larsh, T. R., Marcogliese, P. C. & Pena, L. D. M. in GeneReviews(®) (eds M. P. Adam et al. ) (University of Washington, Seattle Copyright © 1993-2025, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved., 1993). Venkateswaran, S. et al. IRF2BPL-Related Disorder, Causing Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech and Seizures (NEDAMSS) Is Characterized by Pathology Consistent with DRPLA. Mov Disord 39 , 2102-2109 (2024). https://doi.org:10.1002/mds.29938 Chen, P. S. et al. Genetic analysis of IRF2BPL in a Taiwanese dystonia cohort: The genotype and phenotype correlation. Ann Clin Transl Neurol 11 , 1557-1566 (2024). https://doi.org:10.1002/acn3.52072 Marcogliese, P. C. et al. IRF2BPL Is Associated with Neurological Phenotypes. Am J Hum Genet 103 , 245-260 (2018). https://doi.org:10.1016/j.ajhg.2018.07.006 Lou, X. et al. Clinical characterization of IRF2BPL mutation: Case series and review of the literature. Medicine (Baltimore) 104 , e41078 (2025). https://doi.org:10.1097/md.0000000000041078 Bauersachs, D., Bomholtz, L., Del Rey Mateos, S., Kühn, R. & Lisowski, P. Novel human neurodevelopmental and neurodegenerative disease associated with IRF2BPL gene variants-mechanisms and therapeutic avenues. Front Neurosci 18 , 1426177 (2024). https://doi.org:10.3389/fnins.2024.1426177 Tran Mau-Them, F. et al. De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy. Genet Med 21 , 1008-1014 (2019). https://doi.org:10.1038/s41436-018-0143-0 Spagnoli, C., Rizzi, S., Salerno, G. G., Frattini, D. & Fusco, C. IRF2BPL gene variants: One new case. Am J Med Genet A 182 , 255-256 (2020). https://doi.org:10.1002/ajmg.a.61401 Prilop, L. et al. IRF2BPL mutation causes nigrostriatal degeneration presenting with dystonia, spasticity and keratoconus. Parkinsonism Relat Disord 79 , 141-143 (2020). https://doi.org:10.1016/j.parkreldis.2020.03.030 Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterialforReviewandPublication.docx 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. 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2","display":"","copyAsset":false,"role":"figure","size":249247,"visible":true,"origin":"","legend":"\u003cp\u003eEEG findings: generalized high-amplitude slow waves, polyspike-slow waves.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7319210/v1/3598ea5f7df92378ae849683.png"},{"id":92048207,"identity":"c64b30fb-f2e1-4f64-bb50-d585a41c9f7d","added_by":"auto","created_at":"2025-09-24 05:12:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":72566,"visible":true,"origin":"","legend":"\u003cp\u003eHeterozygous \u003cem\u003eIRF2BL\u003c/em\u003e gene mutation (c.499C\u0026gt;T, p.Gln167*) of the patient:\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7319210/v1/1aa8711b49e69b86feb48097.png"},{"id":94823064,"identity":"fb6a216e-ac64-4045-87d1-23f45a98af56","added_by":"auto","created_at":"2025-10-31 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located on chromosome 14q24.3, encoding the interferon regulatory factor 2 binding protein (IRF2BPL). While the exact biological function of this gene is not fully understood, it plays an essential role in neuronal development and maintenance\u003csup\u003e1\u003c/sup\u003e. Mutations in \u003cem\u003eIRF2BPL\u003c/em\u003e can lead to \u003cem\u003eIRF2BPL\u003c/em\u003e-related disorder, also known as neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures (NEDAMSS). This is a rare neurogenetic disorder, with fewer than 70 cases reported\u003csup\u003e2,3\u003c/sup\u003e. The main symptoms of NEDAMSS include developmental delay and seizures, with movement symptoms as the initial presentation being rare. Although movement symptoms (such as dystonia) are common in \u003cem\u003eIRF2BPL\u003c/em\u003e-related disorder, there are relatively few reports on its clinical features and treatment, especially the impact of dystonia on the patient's quality of life. This case presents a patient with cervical dystonia as the initial symptom and explores the potential of botulinum toxin treatment in managing movement symptoms, offering new insights into treating this condition.\u003c/p\u003e"},{"header":"Case summary","content":"\u003cp\u003eThe patient is a 17-year-old female who developed involuntary leftward head rotation and mild lower limb tremors at the age of 14.The head rotation was approximately 75\u0026deg;, accompanied by tremor and sensory tricks. However, the lower limb symptoms were not initially noted. She was diagnosed with cervical dystonia and treated with botulinum toxin injections, which led to complete resolution of her symptoms. Over the following three years, the patient developed dysarthria, which progressively worsened. At age 17, the lower limb tremors became more pronounced, occurring several times a day with multiple falls during standing and walking. Upper limb tremors began to appear, and fine motor tasks such as writing were affected. There was no loss of consciousness during the episodes, and symptoms were more prominent during emotional stress. However, the cervical dystonia symptoms did not relapse. The patient had normal growth and development during childhood. Her grandfather passed away from motor neuron disease at the age of 49. Neurological examination revealed myoclonus in the limbs, and cognitive assessment showed mild cognitive impairment (MMSE score of 26).\u003c/p\u003e\u003cp\u003eBrain MRIs at the ages of 14 and 17 were unremarkable (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). EEG at both ages revealed generalized high-amplitude slow waves and polyspike-slow waves (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), leading to the diagnosis of myoclonic epilepsy. Whole-exome sequencing revealed a novel mutation in the \u003cem\u003eIRF2BPL\u003c/em\u003e gene (NM_024496), *c.499C\u0026thinsp;\u0026gt;\u0026thinsp;T (p.Gln167*)(Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), which introduces a premature stop codon, resulting in a truncated protein. This mutation was not found in the patient\u0026rsquo;s parents. Based on the clinical presentation and genetic findings, the diagnosis of \u003cem\u003eIRF2BPL\u003c/em\u003e-related disorder was confirmed. The patient was treated with carbamazepine (half tablet, once a day), which led to mild alleviation of myoclonic seizures, though the dysarthria did not significantly improve.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe report a case of \u003cem\u003eIRF2BPL\u003c/em\u003e-related disorder with cervical dystonia as the initial symptom. The patient initially presented with cervical dystonia, which was completely resolved with botulinum toxin injection. To date, there have been no reports on botulinum toxin for the treatment of dystonia associated with \u003cem\u003eIRF2BPL\u003c/em\u003e-related disorder.\u003c/p\u003e\u003cp\u003eA literature search reveals 66 reported cases of \u003cem\u003eIRF2BPL\u003c/em\u003e-related disorder (Supplementary Table\u0026nbsp;1). The onset symptoms in these patients varied widely, including developmental abnormalities (18 cases) and various forms of seizures (such as myoclonic seizures, tonic seizures, infantile spasms, etc., 10 cases). Among these cases, only one patients had generalized dystonia at onset, \u003csup\u003e4\u003c/sup\u003e, and another with lower limb dystonia \u003csup\u003e5\u003c/sup\u003e. Therefore, accurate diagnosis is challenging in the early stages of this disease. We report that in this case, the patient's lower limb symptoms were initially overlooked, and the diagnosis focused solely on the prominent cervical dystonia. This case highlights the importance of considering other signs when dystonia is prominent in the early stages, to avoid misdiagnosis.\u003c/p\u003e\u003cp\u003eAlthough movement symptoms are uncommon in the early stages of the disease, most patients (43/67) will gradually develop one or more movement disorder symptoms as the disease progresses. These symptoms include ataxia (28/43), speech delay or dysarthria (27/43), dystonia (20/43), difficulty walking or unstable gait (18/43), dysphagia (12/43), hypotonia (6/43), chorea (3/43), dance-like movements (2/43), postural instability (2/43), and tremor (1/43). These movement symptoms significantly affect the patients' quality of life. However, due to the severity of seizures and developmental delay, the urgency of treating movement symptoms is often overlooked. Treatment of \u003cem\u003eIRF2BP\u003c/em\u003eL-related disorder has primarily focused on seizure control \u003csup\u003e6,7\u003c/sup\u003e. with limited attention to movement symptoms. Few cases have attempted treatment with baclofen, clonazepam, and levodopa, but the effectiveness of these treatments has been poorly reported, with limited success in alleviating movement symptoms. \u003csup\u003e8\u0026ndash;10\u003c/sup\u003e In contrast, botulinum toxin injection offers a novel treatment option for \u003cem\u003eIRF2BP\u003c/em\u003eL-related disorder associated with dystonia. Botulinum toxin works by inhibiting the signaling between nerves and muscles, effectively reducing muscle hypertonia, especially in cervical dystonia and other types of dystonia. This treatment method has provided the patient with three years of symptom relief without relapse, indicating its strong therapeutic effect on \u003cem\u003eIRF2BPL\u003c/em\u003e-related movement symptoms.\u003c/p\u003e\u003cp\u003eIn this case, genetic testing revealed a novel mutation in the \u003cem\u003eIRF2BPL\u003c/em\u003e gene (c.499C\u0026thinsp;\u0026gt;\u0026thinsp;T, p.Gln167*), leading to a premature stop codon and a truncated protein. This mutation has not been previously reported, thus expanding the genetic variation spectrum of IRF2BPL-related syndrome and providing new insights into the genetic mechanisms of the disease. The \u003cem\u003eIRF2BPL\u003c/em\u003e gene plays a crucial role in neuronal development and maintenance, and this mutation may lead to the loss of protein function, affecting normal neurodevelopment and function.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBotulinum toxin injection is a feasible therapy for \u003cem\u003eIRF2BP\u003c/em\u003eL-related disorder patients who develop dystonia. Additionally, when diagnosing these patients, other signs should be carefully considered to avoid misdiagnosis due to the prominence of dystonia, ensuring early and accurate diagnosis and timely intervention.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eNEDAMSS:\u003c/strong\u003e neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizure\u003cstrong\u003es\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIRF2BPL:\u0026nbsp;\u003c/strong\u003einterferon regulatory factor 2 binding protein\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEEG:\u0026nbsp;\u003c/strong\u003eelectroencephalogram\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMMSE:\u0026nbsp;\u003c/strong\u003emini-mental state examination\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMRI:\u0026nbsp;\u003c/strong\u003emagnetic resonance imaging\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw sequencing data generated during the current study are available in the Genome Sequence Archive for Human (GSA-Human) under accession number HRA019750.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by National High Level Hospital Clinical Research Funding(2022-PUMCH-B-018).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors and Affiliations\u003c/p\u003e\n\u003cp\u003eDepartment of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, China 100730\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYL:\u0026nbsp;\u0026nbsp;analysis and interpretation of data, manuscript writing and literature search; ZMW : patient follow-up examination; XHW: reviewed and substantively revised the paper\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to XinHua Wan\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThe study participants were reviewed and approved by the Medical Review Ethics Committee of the Peking Union Medical College Hospital (reference number: I-24PJ0207). All participants provided written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of clinical details was obtained from the patient\u0026rsquo;s parents (legal guardians).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSinha Ray, S.\u003cem\u003e et al.\u003c/em\u003e Mechanisms of IRF2BPL-related disorders and identification of a potential therapeutic strategy. \u003cem\u003eCell Rep\u003c/em\u003e \u003cstrong\u003e41\u003c/strong\u003e, 111751 (2022). https://doi.org:10.1016/j.celrep.2022.111751\u003c/li\u003e\n\u003cli\u003eVanagunas, T., Ulm Seiwert, E., Larsh, T. R., Marcogliese, P. C. \u0026amp; Pena, L. D. M. in \u003cem\u003eGeneReviews(\u0026reg;)\u003c/em\u003e (eds M. P. Adam\u003cem\u003e et al.\u003c/em\u003e) (University of Washington, Seattle Copyright \u0026copy; 1993-2025, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved., 1993).\u003c/li\u003e\n\u003cli\u003eVenkateswaran, S.\u003cem\u003e et al.\u003c/em\u003e IRF2BPL-Related Disorder, Causing Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech and Seizures (NEDAMSS) Is Characterized by Pathology Consistent with DRPLA. \u003cem\u003eMov Disord\u003c/em\u003e \u003cstrong\u003e39\u003c/strong\u003e, 2102-2109 (2024). https://doi.org:10.1002/mds.29938\u003c/li\u003e\n\u003cli\u003eChen, P. S.\u003cem\u003e et al.\u003c/em\u003e Genetic analysis of IRF2BPL in a Taiwanese dystonia cohort: The genotype and phenotype correlation. \u003cem\u003eAnn Clin Transl Neurol\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 1557-1566 (2024). https://doi.org:10.1002/acn3.52072\u003c/li\u003e\n\u003cli\u003eMarcogliese, P. C.\u003cem\u003e et al.\u003c/em\u003e IRF2BPL Is Associated with Neurological Phenotypes. \u003cem\u003eAm J Hum Genet\u003c/em\u003e \u003cstrong\u003e103\u003c/strong\u003e, 245-260 (2018). https://doi.org:10.1016/j.ajhg.2018.07.006\u003c/li\u003e\n\u003cli\u003eLou, X.\u003cem\u003e et al.\u003c/em\u003e Clinical characterization of IRF2BPL mutation: Case series and review of the literature. \u003cem\u003eMedicine (Baltimore)\u003c/em\u003e \u003cstrong\u003e104\u003c/strong\u003e, e41078 (2025). https://doi.org:10.1097/md.0000000000041078\u003c/li\u003e\n\u003cli\u003eBauersachs, D., Bomholtz, L., Del Rey Mateos, S., K\u0026uuml;hn, R. \u0026amp; Lisowski, P. Novel human neurodevelopmental and neurodegenerative disease associated with IRF2BPL gene variants-mechanisms and therapeutic avenues. \u003cem\u003eFront Neurosci\u003c/em\u003e \u003cstrong\u003e18\u003c/strong\u003e, 1426177 (2024). https://doi.org:10.3389/fnins.2024.1426177\u003c/li\u003e\n\u003cli\u003eTran Mau-Them, F.\u003cem\u003e et al.\u003c/em\u003e De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy. \u003cem\u003eGenet Med\u003c/em\u003e \u003cstrong\u003e21\u003c/strong\u003e, 1008-1014 (2019). https://doi.org:10.1038/s41436-018-0143-0\u003c/li\u003e\n\u003cli\u003eSpagnoli, C., Rizzi, S., Salerno, G. G., Frattini, D. \u0026amp; Fusco, C. IRF2BPL gene variants: One new case. \u003cem\u003eAm J Med Genet A\u003c/em\u003e \u003cstrong\u003e182\u003c/strong\u003e, 255-256 (2020). https://doi.org:10.1002/ajmg.a.61401\u003c/li\u003e\n\u003cli\u003ePrilop, L.\u003cem\u003e et al.\u003c/em\u003e IRF2BPL mutation causes nigrostriatal degeneration presenting with dystonia, spasticity and keratoconus. \u003cem\u003eParkinsonism Relat Disord\u003c/em\u003e \u003cstrong\u003e79\u003c/strong\u003e, 141-143 (2020). https://doi.org:10.1016/j.parkreldis.2020.03.030\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":"IRF2BPL, NEDAMSS, dystonia, neurodegeneration, botulinum","lastPublishedDoi":"10.21203/rs.3.rs-7319210/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7319210/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003e\u003cem\u003eIRF2BPL\u003c/em\u003e-related disorder ,also known as neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, NEDAMSS, is a rare neurogenetic disorder. It typically presents with developmental delay or seizures as the initial symptoms. This report describes a case of \u003cem\u003eIRF2BPL\u003c/em\u003e mutation with cervical dystonia as the initial symptom and further explores the treatment strategies for movement symptoms.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e\u003cp\u003eA 17-year-old female presented with involuntary leftward head rotation and mild lower limb tremors three years ago. She was diagnosed with cervical dystonia, and after receiving botulinum toxin injections, her symptoms completely resolved. In the following three years, the patient developed worsening lower limb tremors, diagnosed as myoclonic seizures based on EEG findings, along with dysarthria and ataxia. Whole-exome sequencing confirmed the \u003cem\u003eIRF2BPL\u003c/em\u003e mutation, and the final diagnosis was \u003cem\u003eIRF2BPL\u003c/em\u003e-related syndrome. The patient was treated with carbamazepine, which alleviated the tremor symptoms.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThe treatment of \u003cem\u003eIRF2BPL\u003c/em\u003e-related disorder primarily focuses on seizure control, while movement symptoms, such as dystonia, significantly affect the patient's quality of life but are often overlooked. In this case, botulinum toxin effectively controlled the patient's dystonia, providing a new approach to treating movement symptoms.\u003c/p\u003e","manuscriptTitle":"Cervical Dystonia as the Initial Symptom of IRF2BPL-related Disorder: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-24 05:12:37","doi":"10.21203/rs.3.rs-7319210/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":"375b5ed7-c262-40b5-b7e2-7f06781b91ad","owner":[],"postedDate":"September 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-30T07:39:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-24 05:12:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7319210","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7319210","identity":"rs-7319210","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}