Brain & Development最新文献

{"title":"Motor skills and neurological soft signs: Are they only clinical differences or reflection of distinct etiopathogenesis in tic disorder and primary stereotypic movement disorder?","authors":"Ecem Selin Akbas Aliyev ,&nbsp;Dilek Ünal","doi":"10.1016/j.braindev.2025.104377","DOIUrl":"10.1016/j.braindev.2025.104377","url":null,"abstract":"<div><h3>Background</h3><div>While tic disorders and stereotypic movement disorder are commonly comorbid in pediatric clinics, their clinical and etiological differences remain poorly understood.</div></div><div><h3>Objectives</h3><div>We aimed to investigate the clinical features that differentiate between tic disorders and primary stereotypic movement disorder by evaluating neurological soft signs and motor skills.</div></div><div><h3>Methods</h3><div>The Kiddie-Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version DSM-5 and Sociodemographic and Clinical Data Form were administered to the children. The clinician completed Yale Global Tic Severity Scale, Repetitive Behavior Scale-Revised and Neurological Evaluation Scale. Nine-Hole Peg Test was used for fine motor skills, 1-Minute Sit-to-Stand Test for gross motor skills, Flamingo Balance Test for static balance, Finger-to-Nose Test for bilateral coordination. Parents completed the Conners Parent Rating Scale-Revised Short Form and the Revised Developmental Coordination Disorder Questionnaire.</div></div><div><h3>Results</h3><div>Our sample consisted of 20 tic disorders, 20 primary stereotypic movement disorder, 13 attention deficit hyperactivity disorder patients, and 20 healthy controls. Sequencing of the complex motor acts scores of Neurological Evaluation Scale were significantly higher in the primary stereotypy group than in healthy controls. The primary stereotypy group demonstrated significantly lower dominant hand performance on the Nine-Hole Peg Test than the tic group. Children with stereotypy had significantly lower scores of 1-min sit-to-stand test; higher total and subscale scores of Revised Developmental Coordination Disorder Questionnaire. and higher developmental coordination disorder risk than healthy controls.</div></div><div><h3>Conclusions</h3><div>Our findings offer valuable insights into the distinct etiopathogenesis of tic disorders and primary stereotypic movement disorder, providing a foundation for future neurobiological research.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104377"},"PeriodicalIF":1.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term outcome prediction after pediatric cardiac arrest by continuous electroencephalography","authors":"Eri Ohashi ,&nbsp;Itaru Hayakawa ,&nbsp;Hiroki Kato ,&nbsp;Kentaro Ide ,&nbsp;Shotaro Matsumoto ,&nbsp;Kyongsun Pak ,&nbsp;Yuichi Abe","doi":"10.1016/j.braindev.2025.104375","DOIUrl":"10.1016/j.braindev.2025.104375","url":null,"abstract":"<div><h3>Objective</h3><div>Continuous electroencephalography (cEEG) features after cardiac arrest (CA) are associated with short-term outcome predictions. However, the association between cEEG features and long-term neurobehavioral outcomes in children remains unclear. This study aimed to identify cEEG features that can accurately predict neurobehavioral outcomes in children 6 months after CA.</div></div><div><h3>Methods</h3><div>A single-center, retrospective, observational study was performed at the tertiary care pediatric intensive care unit (PICU) of a national children's hospital. This study included a consecutive cohort of children admitted to the PICU after CA who underwent cEEG monitoring. The initial EEG background, electrographic seizures, and changes in EEG background over time were documented for each time point. The primary outcome was neurobehavioral outcomes at 6 months after resuscitation. To assess the reliability of the predictive model, the area under the receiver operating characteristic curve (AUROC) of models was compared for different combinations of EEG features.</div></div><div><h3>Results</h3><div>The study included 62 infants and children. Unfavorable neurobehavioral outcomes were reported in 39 patients (63 %), including mortality in 20 patients. The combination of initial EEG background category and the EEG change from initial EEG initiation to 24 h, or variability/reactivity alone, were minimal optimal predictive models for unfavorable neurobehavioral outcomes at 6 months (AUROC, 0.99 [95 % confidence interval, 0.98–1.00], and 0.99 [95 % confidence interval 0.97–1.00], respectively).</div></div><div><h3>Conclusions</h3><div>Early cEEG features in the PICU can accurately predict neurobehavioral outcomes in children at 6 months after CA. These results can enhance prognostication and guide clinical decision-making in pediatric CA cases.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104375"},"PeriodicalIF":1.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-resistant epilepsy in children post-neonatal seizures: Clinical profiles and predictors","authors":"Warisara Saenchai ,&nbsp;Satit Manopunya ,&nbsp;Shanika Kosarat ,&nbsp;Varangthip Khuwuthyakorn ,&nbsp;Watcharee Tantiprabha ,&nbsp;Kamornwan Katanyuwong ,&nbsp;Chinnuwat Sanguansermsri ,&nbsp;Natrujee Wiwattanadittakul","doi":"10.1016/j.braindev.2025.104373","DOIUrl":"10.1016/j.braindev.2025.104373","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the clinical profile, etiologies, and outcomes of neonatal seizures and identify predictors of drug-resistant epilepsy (DRE) in children.</div></div><div><h3>Method</h3><div>A retrospective chart review was performed on neonates with seizures admitted to Chiang Mai University Hospital, Thailand, from January 2008 to December 2023. The diagnosis of neonatal seizures was based on clinical findings and/or electroencephalography. Severe impairment refers to limited mobility and minimal speech, while profound impairment indicates being bedridden. DRE is defined as the failure of two antiseizure medications to control seizures.</div></div><div><h3>Results</h3><div>Among 218 patients (58.3 % male), the median seizure onset was 12 h (interquartile range [IQR]: 2.9–87 h). The leading etiology was perinatal asphyxia (58.7 %), followed by hemorrhage (7.8 %). The median follow-up was 27 months (IQR: 31.5 months). Epilepsy developed in 39 (27.3 %) patients, with 19 (48.7 %) meeting DRE criteria. Risk factors for epilepsy included marked abnormal neuroimaging, refractory neonatal seizures and severe to profound developmental impairment (<em>P</em> &lt;0.05). In the multivariate model, profound developmental impairment (odds ratio [OR] = 2.89, <em>p</em> = 0.04, 95 % confidence interval [CI]: 1.79–24.19) and the development of epileptic spasms or multiple seizure types (OR = 114.80, <em>p</em> = 0.01, 95 % CI: 4.79–2746.07) were identified as an independent risk factor for DRE.</div></div><div><h3>Conclusion</h3><div>Perinatal asphyxia is the most common cause of neonatal seizures. One-third of neonates with seizures developed epilepsy, with half of them meeting the criteria for DRE. Neonates who develop epileptic spasms, exhibit multiple seizure types, or have profound developmental impairment are key DRE predictors.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104373"},"PeriodicalIF":1.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MECP2 duplication syndrome: Recent advances in pathophysiology and therapeutic perspectives","authors":"Yuichi Akaba ,&nbsp;Satoru Takahashi","doi":"10.1016/j.braindev.2025.104371","DOIUrl":"10.1016/j.braindev.2025.104371","url":null,"abstract":"<div><div><em>MECP2</em> duplication syndrome (MDS) is an X-linked neurodevelopmental disorder caused by duplication or extra copies of <em>MECP2</em> gene. It primarily affects males and is characterized by intellectual disability, hypotonia, epilepsy, recurrent infections, and autistic features. Methyl-CpG binding protein 2 (MeCP2) encoded by <em>MECP2</em> is a crucial epigenetic regulator of brain function. Expression levels are strictly regulated during brain development and maturation, and altered levels lead to severe neurodevelopmental disorders; excessive levels are associated with MDS, while insufficient levels cause Rett syndrome. This review provides a comprehensive overview of the recent advances in the pathophysiology and therapeutic perspectives of MDS, focusing on its pathophysiology, clinical features, disease models, and therapeutic strategies. Advances in studies using animal and patient-derived induced pluripotent stem cells (iPSCs)-derived neuronal models have provided insights into the molecular and cellular abnormalities associated with MDS and have facilitated therapeutic development. Among the emerging treatments, antisense oligonucleotide (ASO) therapy has gained significant attention as a promising approach for selectively suppressing MeCP2 overexpression. Preclinical studies using MDS mouse models and iPSCs-derived neurons have demonstrated that ASO treatment can partially restore neuronal abnormalities and clinical trials are currently underway.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104371"},"PeriodicalIF":1.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144072210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JSCN Best Paper Awards","authors":"","doi":"10.1016/j.braindev.2025.104372","DOIUrl":"10.1016/j.braindev.2025.104372","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 3","pages":"Article 104372"},"PeriodicalIF":1.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Awareness and knowledge of pediatricians regarding genetic testing for Fragile X syndrome in Japan: A National Survey of Pediatricians Managing Developmental Delay/Intellectual disability","authors":"Tetsuya Okazaki ,&nbsp;Chisako Aoki ,&nbsp;Saki Shinzato ,&nbsp;Kaori Adachi ,&nbsp;Eiji Nanba","doi":"10.1016/j.braindev.2025.104367","DOIUrl":"10.1016/j.braindev.2025.104367","url":null,"abstract":"<div><h3>Background</h3><div>Fragile X syndrome (FXS) commonly cause developmental delay, intellectual disability, and autism spectrum disorder. Although genetic testing has been available and included in Japan's national health insurance since 2016, the number of cases diagnosed with FXS remains low. This study aimed to explore the levels of awareness and understanding of FXS among pediatricians managing developmental delay/ intellectual disability in Japan, particularly between pediatrician with and without clinical genetics certification (or clinical experience with FXS).</div></div><div><h3>Methods</h3><div>A survey involving 1217 certified pediatric neurologists from the Japanese Society of Pediatric Neurology and 367 members of the Japanese Society of Pediatric Genetics was conducted. Additional participants were recruited from an online mailing list of 1469 pediatric neurologists. The survey comprised questions on demographics, knowledge about FXS, and genetic testing practices. The responses were analyzed using Chi-square and Fisher's exact tests, and a <em>p</em>-value &lt;0.05 was considered statistically significant.</div></div><div><h3>Results</h3><div>Out of 386 respondents, 326 had experience ordering some kind of genetic testing, including 78 certified clinical geneticists. Knowledge gaps were significant between clinical geneticists and non-genetic specialists. While 20 % of non-genetic specialists were unaware of insurance-covered FXS genetic testing, this percentage was lower among those with clinical experience in FXS cases. Many respondents, irrespective of certification, struggled to determine the indications for requesting FXS genetic testing. Furthermore, non-genetic specialists reported more difficulty providing genetic counseling owing to the psychological burden on mothers.</div></div><div><h3>Conclusion</h3><div>This study highlights the necessity for expanding education and training on FXS among pediatricians in Japan. Addressing these knowledge gaps may enhance FXS diagnostic rates and improve the management of affected individuals and families. Future efforts should focus on strengthening the collaboration between clinical geneticists and general pediatricians and establishing reliable genetic counseling support systems.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104367"},"PeriodicalIF":1.4,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The first case of Al-Raqad syndrome in Japan is associated with a homozygous DCPS exonic variant resulting in aberrant splicing","authors":"Haruka Nozaki ,&nbsp;Nana Sakakibara ,&nbsp;Hiroaki Hanafusa ,&nbsp;Yuta Inoki ,&nbsp;Yu Tanaka ,&nbsp;Hideaki Kitakado ,&nbsp;Chika Ueda ,&nbsp;China Nagano ,&nbsp;Tomoko Horinouchi ,&nbsp;Tomohiko Yamamura ,&nbsp;Shingo Ishimori ,&nbsp;Hiroshi Yamaguchi ,&nbsp;Kandai Nozu ,&nbsp;Naoya Morisada","doi":"10.1016/j.braindev.2025.104366","DOIUrl":"10.1016/j.braindev.2025.104366","url":null,"abstract":"<div><h3>Background</h3><div>Cases of unexplained neurodevelopmental disorder (NDD) are often accompanied by multiple congenital anomalies. With recent advances in genetic analysis technology, whole-exome sequencing (WES) has become a powerful diagnostic tool for unexplained NDD patients, but variants of unknown significance are sometimes detected in them.</div></div><div><h3>Methods</h3><div>WES identified a variant in a 2-year-old boy with NDD associated with multiple congenital anomalies who had no abnormal findings in G-banding and array comparative genomic hybridization (array CGH). mRNA analysis was performed on the variant using the patient's peripheral blood leukocytes following <em>in silico</em> analysis to confirm its effect on splicing.</div></div><div><h3>Results</h3><div>WES revealed a novel homozygous single base substituting variant of unknown significance (VUS), which was carried heterozygously by the patient's parents (<em>DCPS</em>, <span><span>NM_014026.6</span><svg><path></path></svg></span>: c.200A&gt;G, p.(Lys67Arg)). <em>In silico</em> analysis predicted that this variant may cause aberrant splicing, and mRNA analysis revealed a 48-bp deletion from the 3′ end of exon 1. Biallelic variants of <em>DCPS</em> are known to cause Al-Raqad syndrome, a quite rare disorder which presents NDD with multiple malformations. This disease has been reported in only eight individuals from five Middle Eastern or Caucasian families but never in the Japanese but the symptoms of the present case were similar to reported cases of this syndrome.</div></div><div><h3>Discussion</h3><div>We successfully diagnosed a case of unexplained NDD as Al-Raqad syndrome by WES along with mRNA analysis. Single base substitution with judged VUS can be pathogenic by causing aberrant splicing and, therefore, <em>in silico</em> analysis and subsequent RNA sequence are necessary to prove its pathogenicity.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104366"},"PeriodicalIF":1.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a manual for an upper extremity intensive rehabilitation program for pediatric hemiplegia in Japan and assessment of its effectiveness and usability","authors":"Sayaka Katori ,&nbsp;Yukihiro Kitai ,&nbsp;Ryo Tanabe ,&nbsp;Yusuke Kawahara ,&nbsp;Masaki Miura ,&nbsp;Etsushi Toyoda","doi":"10.1016/j.braindev.2025.104364","DOIUrl":"10.1016/j.braindev.2025.104364","url":null,"abstract":"<div><h3>Objectives</h3><div>The aim of this study was to develop a manual for an upper extremity intensive rehabilitation program for pediatric hemiplegia in Japan, and to clarify its effectiveness and usability.</div></div><div><h3>Methods</h3><div>The manual was created through discussions among nine experts with sufficient pediatric clinical experience in Japan. A total of 39 children with hemiplegia aged 2 to 16 years underwent 44 intensive therapy sessions using the manual. Each child's upper limb function was assessed pre-, post- and 6-month after the intervention using the Canadian Occupational Performance Measure (COPM), ABILHAND-Kids, the Quality of Upper Extremity Skills Test (QUEST), and Box and Block Test (BBT). Questionnaire assessments were also conducted to evaluate usability of the manual.</div></div><div><h3>Results</h3><div>All four indices showed statistically significant improvements from pre- to post-intervention; COPM improved by 4 points in both performance and satisfaction; the ABILHAND-Kids logit score improved by 0.78; the total QUEST score improved by 2.8 in total score; and BBT improved by 5 on the affected side and 6 on the non-affected side. These effects were maintained 6 months later. Most therapists responded that the manual is useful, and most children and their parents were satisfied with the rehabilitation.</div></div><div><h3>Conclusions</h3><div>An upper extremity intensive rehabilitation program for pediatric hemiplegia using our manual was clinically effective. The manual was useful for therapists, and the level of satisfaction among parents and children who received the therapy was high.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 3","pages":"Article 104364"},"PeriodicalIF":1.4,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Volumetric and microstructural changes in the Hippocampus and cingulum in children with west syndrome","authors":"Özgür PALANCI ,&nbsp;Tülay KAMAŞAK ,&nbsp;Zeliha AYDIN KASAP ,&nbsp;İlker EYÜBOĞLU ,&nbsp;Beril DİLBER ,&nbsp;Ali CANSU","doi":"10.1016/j.braindev.2025.104365","DOIUrl":"10.1016/j.braindev.2025.104365","url":null,"abstract":"<div><h3>Purpose:</h3><div>We aimed to investigate structural changes in the hippocampus using automated segmentation techniques to evaluate the anatomy and function of the hippocampus in patients with West syndrome (WS).</div></div><div><h3>Methods:</h3><div>The study included 48 participants (24 with WS and 24 healthy controls) aged 0‐4 years. Automated segmentation methods were used to measure hippocampal volume and evaluate diffusion tensor imaging (DTI) parameters such as fractional anisotropy (FA) and mean diffusivity (MD). Bonferroni correction was applied for multiple comparisons, setting the adjusted significance threshold at <em>p</em> &lt; 0.0033.</div></div><div><h3>Results:</h3><div>Children with WS exhibited significantly reduced total hippocampal volume and diminished volumes in the CA2–CA3, CA4-dentate gyrus (CA4-DG), and SR-SL-SM regions compared to healthy controls (padj &lt;0.0033). After correction, no significant differences were found in the CA1 and subiculum regions (padj &gt;0.0033). Although initial comparisons between ongoing WS and seizure-controlled WS suggested increased volumes in several hippocampal regions in the seizure-controlled group, these differences did not remain significant after adjustment and must be interpreted with caution. Notably, patients with seizure-controlled WS displayed larger hippocampal volumes, higher FA, and lower MD values, indicating a possible link between seizure activity and structural alterations. Additionally, DTI analysis of the cingulum revealed lower FA and higher MD values in WS patients, suggesting compromised microstructural integrity.</div></div><div><h3>Conclusions:</h3><div>These findings emphasize the potential role of hippocampal alterations in the pathophysiology of WS and suggest that DTI parameters may serve as useful measures for monitoring disease progression and treatment response.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 3","pages":"Article 104365"},"PeriodicalIF":1.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges in genetic counseling for RYR1-related myopathies","authors":"Rina Shimomura ,&nbsp;Yuki Kihara ,&nbsp;Tomoe Yanagishita ,&nbsp;Kumiko Ishiguro ,&nbsp;Minobu Shichiji ,&nbsp;Takatoshi Sato ,&nbsp;Keiko Shimojima Yamamoto ,&nbsp;Yasuki Ishihara ,&nbsp;Miho Nagata ,&nbsp;Yohei Miyashita ,&nbsp;Yoshihiro Asano ,&nbsp;Keiko Ishigaki ,&nbsp;Satoru Nagata ,&nbsp;Toshiyuki Yamamoto","doi":"10.1016/j.braindev.2025.104363","DOIUrl":"10.1016/j.braindev.2025.104363","url":null,"abstract":"<div><h3>Background</h3><div>Ryanodine receptor 1 (<em>RYR1</em>)-related myopathy is inherited in an autosomal dominant (AD) or recessive (AR) manner. We experienced two sporadic cases of <em>RYR1</em>-related myopathy. One patient harbored a de novo missense variant, whereas the other harbored compound heterozygous variants inherited from each parent. The possibility of dual inheritance makes it challenging to distinguish between these two inheritance patterns based only on clinical information.</div></div><div><h3>Methods</h3><div>In this study, PubMed was used to perform literature review on genetic counseling for <em>RYR1</em>-related myopathy.</div></div><div><h3>Results</h3><div>Recently published manuscripts have emphasized the importance of comprehensive genomic analysis of all <em>RYR1</em> coding regions.</div></div><div><h3>Conclusion</h3><div><em>RYR1</em>-related myopathy without family history may be associated with de novo heterozygous AD variants and biallelic involvement in AR. In cases of AR traits, a prenatal diagnosis may be required from the parents. Therefore, precise genetic information is essential for genetic counseling. It would be impossible to assess the inheritance patterns from genotypes only if monoallelic missense variants were identified in patients with congenital myopathy. This review emphasizes the importance of comprehensively analyzing all coding regions using trio samples for better genetic counseling.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 3","pages":"Article 104363"},"PeriodicalIF":1.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}