American Journal of Medical Genetics Part C: Seminars in Medical Genetics最新文献

{"title":"Arthrogryposis Multiplex Congenita in Pediatric Age: Correlation Between MUScular MRI and Functional Evaluation (AMUSE), Toward a Biomechanical Model.","authors":"Alicia-Marine Milot, Mariya Raykova, Claire Huzar, Véronique Thellier, Nicolas Hergibo, Marjolaine Gauthier, Gipsy Billy-Lopez, Chantal Durand, Frédérique Nugues, Véronique Bourg, Klaus Dieterich","doi":"10.1002/ajmg.c.70024","DOIUrl":"https://doi.org/10.1002/ajmg.c.70024","url":null,"abstract":"<p><p>Arthrogryposis Multiplex Congenita (AMC) is a group of diseases with joint limitations at two or more distinct joint levels at birth. Joint limitations are not progressive, but the functional consequences have a lifelong impact on patients. The management of these conditions is therefore demanding, necessarily multidisciplinary, and is a long-term process. The aim of our study was to evaluate the correlation between muscle fat infiltration and deficiencies and activity limitations in children with AMC. We conducted a monocentric retrospective observational study including patients with exclusive pediatric follow-up evaluated at the AMC Reference Centre (RC) of the University Hospital of Grenoble Alpes between 2010 and 2022. We included 97 patients, of whom 50% had Amyoplasia. We showed that, all groups combined, the Mercuri score was significantly correlated with PROM in the upper and lower limbs, with muscular weakness in the lower limbs, and also with reaching ability. Our study is one of the first in a pediatric population to investigate the link between muscle imaging and functional aspects of AMC. Muscle MRI is a recognized and recommended tool for diagnosis and also a suitable noninvasive tool to assess and assist in the functional prognosis of patients.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding Arthrogryposis Multiplex Congenita (AMC) Across the Lifespan: An Integrative Review of the Adult AMC Registry's Contributions With Lived Experience Partnerships.","authors":"Bonita J Sawatzky, Megan K MacGillivray, Tracey Schalk, William Bennett Mortenson","doi":"10.1002/ajmg.c.70020","DOIUrl":"https://doi.org/10.1002/ajmg.c.70020","url":null,"abstract":"<p><p>This reflective essay explores how collaborative work between researchers and adults living with Arthrogryposis Multiplex Congenita (AMC) has deepened and broadened our understanding of what it means to live with this rare condition. By intentionally integrating the lived experiences of individuals with AMC into research processes, the resulting registry becomes far richer, more representative, and more meaningful. Including people with AMC as co-investigators not only strengthens the quality and relevance of the data collected but also offers participants a sense of agency, ownership, and empowerment within the research journey. This essay highlights a growing shift in rare-disease research toward approaches that prioritize patient-centered knowledge and long-term data collection. As registries become essential tools for understanding rare conditions, the inclusion of lived experience is increasingly recognized as a critical component in shaping their design, development, and ongoing evolution. However, building and sustaining a registry that may span an entire lifetime is not without its challenges. Issues such as maintaining engagement, ensuring accessibility, and navigating the emotional and logistical complexities of long-term participation all require thoughtful consideration. This paper reflects on these complexities while emphasizing the value of collaborative, experience-driven research in advancing understanding of AMC.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain and Health: Sex-Specific Differences From a Survey Study of Adults With Arthrogryposis Multiplex Congenita.","authors":"Jaclyn Megan Sions, Maureen Donohoe, Claire Elizabeth Vallery, Samantha Jeanne Stauffer, Ryan Todd Pohlig","doi":"10.1002/ajmg.c.70021","DOIUrl":"https://doi.org/10.1002/ajmg.c.70021","url":null,"abstract":"<p><p>Arthrogryposis Multiplex Congenita (AMC), a rare congenital condition characterized by joint contractures in two or more body regions, is often accompanied by pain. Understanding pain and its relationship to health outcomes among adults with AMC is critical for effective pain management. The objectives of this survey study were to characterize the pain experience in adults with AMC and determine the extent to which pain intensity relates to health, while considering potential sex differences. Participants (n = 73, 67.3% female) reported average pain intensity, severity, and extent per body diagrams, and completed the Pain Catastrophizing Scale and 29-item Patient-Reported Outcomes Measurement Information System. In the preceding 7 days, 82.7% of participants reported pain; females were more likely to report pain. Pain intensity was significantly greater in females than males. Beyond covariates of sex and AMC severity, higher pain intensity was associated with worse physical function and ability to participate in social roles, as well as greater sleep disturbance. Female sex and an interaction term (sex × pain intensity) were significantly associated with greater fatigue. Findings highlight the importance of considering sex-specific differences in pain and the relationship between pain intensity and fatigue among adults with AMC.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148672812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upper Extremity Entrapment Neuropathies in Adults With Arthrogryposis Multiplex Congenita: A National Database Study.","authors":"Adam Boukind, Andrea Biaggi-Ondina, Aidin R T Apte, Aneri U Patel, Amber R Leis","doi":"10.1002/ajmg.c.70018","DOIUrl":"https://doi.org/10.1002/ajmg.c.70018","url":null,"abstract":"<p><p>Adults with arthrogryposis multiplex congenita (AMC) experience lifelong disability from joint contractures, yet susceptibility to upper extremity compressive neuropathy remains unevaluated. Using the TriNetX US Collaborative Network, we identified 2772 adults with AMC and 100,903,909 controls. Prevalence of upper extremity entrapment neuropathies was compared using prevalence ratios (PR) and 95% confidence intervals, with age-stratified analyses across three strata (18-39, 40-59, and 60-69 years). Adults with AMC demonstrated elevated entrapment neuropathy rates across all distributions. Carpal tunnel syndrome was nearly twice as prevalent (PR 1.84, 95% CI 1.49-2.27), cubital tunnel syndrome nearly four times as prevalent (PR 3.76, 95% CI 2.87-4.91), and proximal neuropathies four- to sixfold more common (PR range 4.77-5.44, all p < 0.001). Electrodiagnostic testing was proportionally less elevated (PR 2.43), arguing against detection bias. Carpal tunnel syndrome comprised a smaller share of diagnoses in AMC versus controls (44% vs. 65%), reflecting pan-upper-extremity involvement. Age-stratified rate ratios increased progressively, reaching 16.43-fold for carpal tunnel syndrome and 74.70-fold for cubital tunnel syndrome in the 60-69 stratum. AMC confers elevated, age-progressive risk for compressive neuropathy across multiple upper extremity distributions, warranting proactive surveillance to prevent further functional impairment and chronic pain.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The International Consortium for Arthrogryposis: A Collaborative Framework for Early Detection, Care, Research, and Education.","authors":"Shahrzad Nematollahi, Noa Bouzaglo, Victoria Castillo Sanchez, Johanna I P de-Vries, Klaus Dieterich, Alicja Fafara, Isabel Filges, Philip Giampietro, Göknur Haliloğlu, Judith Hall, Coleman Hilton, Remco Jansen, Valentina Maestri, Carolina Navalon, Daniel Natera de Benito, Tony Pan, Ani Samargian, Bonita Sawatzky, Harold van Bosse, Paul A Trainor, Noémi Dahan-Oliel","doi":"10.1002/ajmg.c.70013","DOIUrl":"https://doi.org/10.1002/ajmg.c.70013","url":null,"abstract":"<p><p>Arthrogryposis multiplex congenita (AMC) is a group of rare congenital conditions, characterized by multiple joint contractures but may involve any body system including central nervous system. AMC is etiologically heterogeneous, with over 400 genetic and many non-genetic causes implicated in its prenatal development. AMC requires lifelong, multidisciplinary management, a challenge compounded by their rarity and phenotypic heterogeneity. Our understanding of AMC is hampered by diagnostic delays, scarce trained specialists, and variable clinician expertise. Research networks are paramount to harmonize efforts, increase awareness, and accelerate progress toward understanding of rare conditions. Therefore, we established a consortium for AMC (IC4AMC) in 2020, a multi-national network dedicated to improving AMC care, research, and knowledge across North America, Europe, and West Asia. IC4AMC engages a diverse group of stakeholders including clinicians, researchers, individuals with AMC, families, and support groups to better understand and address the most pressing needs in AMC care and research. In this paper, we introduced the missions and aims of the IC4AMC around four pillars of early detection, clinical care, research, and education, all embedded in two cross-cutting principles of knowledge mobilization and community engagement. This effort will inform the development of targeted initiatives aimed at improving outcomes for rare diseases.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caring for Pediatric Clients With Arthrogryposis Multiplex Congenita: The Development of an Occupational Therapy Continuing Education Course.","authors":"Amy Sitabkhan, April Cowan, Amy Boyd, Scott Oishi","doi":"10.1002/ajmg.c.70015","DOIUrl":"https://doi.org/10.1002/ajmg.c.70015","url":null,"abstract":"<p><p>Occupational therapy practitioners (OTPs) are vital members of the multidisciplinary team involved in caring for pediatric clients diagnosed with arthrogryposis multiplex congenita (AMC). However, a shortage of educational resources on AMC has led to gaps in knowledge and OTPs feeling inadequately prepared to provide comprehensive care. A 4-h continuing education (CE) course on caring for pediatric clients with AMC was designed using evidence-based literature and structured using the person-environment-occupation model. The occupation-based model guided learners to understand how therapy can intervene to improve occupational performance. The course was presented at the Texas Occupational Therapy Association 2024 Conference. Ten learners completed a pre- and postcourse examination, pre- and postcourse self-assessment, and course evaluation. Results indicated significant changes (p < 0.001) in knowledge acquisition, awareness, and preparedness to care for pediatric clients with AMC. Learners expressed greater clinical reasoning following the completion of clinical vignettes and hands-on activities. Overall, learners found the course to be well-developed. The development and implementation of the CE course led to significant changes in learners' awareness and preparedness to treat pediatric clients with AMC. OTPs should utilize advanced training CE courses based on learning theories and hands-on training opportunities to ensure safe and appropriate care. Future research should investigate longitudinal changes in learning and the impact of course design on learning.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148269758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apical Ectodermal Ridge Disruption and Hypoplastic Digits in Amyoplasia.","authors":"Amanda Stutman, Natalie Williams, Sarah Nossov, Dan Zlotolow","doi":"10.1002/ajmg.c.70016","DOIUrl":"https://doi.org/10.1002/ajmg.c.70016","url":null,"abstract":"<p><p>The cause of Amyoplasia remains controversial, with the predominant theory being loss of anterior horn cells secondary to vascular disruption as the primary insult. Disruption of the apical ectodermal ridge (AER) is extremely rare, occurring in 1 in 2 million live births. Amyoplasia has an incidence of 1 in 10,000 births, making the probability of both conditions occurring simultaneously by chance 1 out of 20 billion. Muscle precursor cells do not differentiate until they reach the limb and contact signaling factors that are AER dependent. Without sufficient AER function, muscle cell line development may be limited. We report on an association between disruption of the AER and Amyoplasia, which may offer a clue regarding pathogenesis. We identified 22 patients who presented to our institution during a 2-year time span. Inclusion criteria include diagnosis of Amyoplasia and at least one hypoplastic digit. Five children were excluded due to lack of data or unconfirmed diagnoses. Radiographs, clinical photos, clinic visit notes, and operative reports were reviewed for this project. Hypoplastic fingers were seen in 41% of cases, hypoplastic toes in 47%, hypoplastic fingers and toes in 6%, and loss of a foot in 6%. No patient had fully preserved ectoderm at the transverse amputation or amniotic bands. Loss of AER function with resultant hypodactyly could be a characteristic of Amyoplasia. There may be a causal or downstream association between AER loss and muscle hypo-development.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The EXPLAIN Study: Exploring Arthrogryposis Multiplex Congenita in Adults in Norway - A Description of Demographic, Medical, and Neurological Findings.","authors":"My Vuong Hermansen, Kristin Ørstavik, Unni Steen, Mathias Toft, Cathrine Brunborg, Lena Lande Wekre","doi":"10.1002/ajmg.c.70017","DOIUrl":"https://doi.org/10.1002/ajmg.c.70017","url":null,"abstract":"<p><p>Arthrogryposis Multiplex Congenita (AMC) encompasses several hundred conditions with diverse genetic, pathophysiological, and clinical origins. The overarching EXPLAIN study explores underlying causes and implications of AMC and represents the largest clinical cohort of adults with AMC reported to date. This part of the EXPLAIN study aims to describe demographic, medical, and neurological findings in adults with AMC in Norway. A complete social, medical, and surgical history was therefore obtained, and the clinical examination comprised phenotype descriptions, anthropometry, neurological and neurophysiological tests, and blood analyses. Seventy-two adults (44 women), 18 to 80 years, were included. 57% reported neurological disease or symptoms. Spinal or truncal involvement was observed in 63%, and craniofacial malformations were observed in 36%. Central nervous system involvement frequently manifested as sensory hearing impairment (26%) and ophthalmoplegia (18%). Peripheral features included axial muscle weakness (53%), areflexia (44%), and hypotonia (40%). Neurogenic changes were identified in 61% of electrophysiological studies, with 31% showing sensory-motor neuropathy. Medical follow-up was required in 75%. This study highlights significant phenotypic variability in socioeconomic factors, medical comorbidities, and clinical presentation of AMC. The prevalence of musculoskeletal and neurological variations emphasizes the need for multidisciplinary care throughout life.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spinal Involvement in a Pediatric and Adult Cohort of Patients With Arthrogryposis Multiplex Congenita.","authors":"Alicia Mom, Véronique Bourg, Shenhao Dai, Alicia-Marine Milot, Dominic Perennou, Klaus Dieterich","doi":"10.1002/ajmg.c.70009","DOIUrl":"https://doi.org/10.1002/ajmg.c.70009","url":null,"abstract":"<p><p>This was a single-center retrospective observational study with national recruitment from October 2007 to March 2022 at the AMC clinic of the University Hospital Grenoble Alpes (CHUGA). Participants underwent a clinical spinal assessment and spine radiography. Our main objective was to analyze the type of spinal involvement within each AMC subgroup. We hypothesized that there was a difference in the prevalence of scoliosis between subgroups. Arthrogryposis multiplex congenita (AMC) is classified into three subgroups (amyoplasia, distal arthrogryposis [DA], \"other causes\") according to their phenotype and underlying etiologies. We carried out comparative statistical analyses between AMC subgroups within two separate series: children and adults. Our outcome measures were the presence of scoliosis, Cobb angles, and underlying spinal abnormalities. In total, 203 participants were selected; 57 were excluded due to lack of spine film. We then performed a statistical analysis of 146 individuals (101 children, 45 adults). We found an overall prevalence of scoliosis of 46% in children and 78% in adults and an overall prevalence of underlying spinal anomalies of 41% in children and 53% in adults. There was a difference in the prevalence of scoliosis between the three AMC subgroups in children (χ² = 6.8, p = 0.033, v = 0.18). The prevalence of scoliosis was higher in the DA group (47% in children and 78% in adults) and in the group \"other causes\" (65% in children) compared to the amyoplasia group (33% in children and 75% in adults). Cobb angles were greater and spinal abnormalities more prevalent in the DA group than in amyoplasia and \"other causes\" groups. Our data confirm the significant difference in the prevalence of scoliosis between AMC subgroups in children. The high prevalence of scoliosis and spinal abnormalities in all AMC subgroups justifies screening by clinical examination and systematic frontal and sagittal spine x-rays during childhood.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147979731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Splice Variant in ERGIC1 Causes Arthrogryposis Multiplex Congenita-Characterization Using Urine-Derived Cells.","authors":"Lauren Kerr, Paul McKay, Juliana Marulanda, Zenghui Wu, Reggie Hamdy, Sena Tavukcu, Noémi Dahan-Oliel, Frank Rauch","doi":"10.1002/ajmg.c.70012","DOIUrl":"https://doi.org/10.1002/ajmg.c.70012","url":null,"abstract":"<p><p>Arthrogryposis multiplex congenita (AMC) is defined as the presence of joint contractures affecting at least two body regions at birth. Three different ERGIC1 variants have been reported in individuals with AMC. Here, we report on a 16-year-old male with a homozygous ERGIC1 c.250+1G>A variant that was classified as a variant of uncertain significance on trio genome analysis. The proband's phenotype resembled that of previously reported individuals with ERGIC1 variants, but also included an absent patella and advanced bone age, which have not been reported in ERGIC1-related AMC. RNA extracted from urine-derived cells showed a splice defect of exon 4. This caused a deletion of two base pairs from the end of the exon, expected to result in a frameshift and nonsense-mediated decay. This report expands the number of ERGIC1 variants linked to AMC and demonstrates the utility of RNA-based diagnostic methods.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}