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

Myhre Syndrome: New Horizons in Clinical Care, Research and the Pursuit of Therapy. Myhre综合征：临床护理，研究和治疗追求的新视野。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2026-08-31 DOI: 10.1002/ajmg.c.70022

Angela E Lin, Nicola Brunetti-Pierri, Valerie Cormier-Daire

引用次数: 0

Understanding Arthrogryposis Multiplex Congenita (AMC) Across the Lifespan: An Integrative Review of the Adult AMC Registry's Contributions With Lived Experience Partnerships. 在整个生命周期中理解多重先天性关节挛缩（AMC）：对成人AMC登记对生活经验伙伴关系贡献的综合回顾。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2026-08-28 DOI: 10.1002/ajmg.c.70020

Bonita J Sawatzky, Megan K MacGillivray, Tracey Schalk, William Bennett Mortenson

{"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":"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.","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}

引用次数: 0

I Breathed. 我呼吸。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2026-08-28 DOI: 10.1002/ajmg.c.70019

Patti M Schultz

引用次数: 0

Pain and Health: Sex-Specific Differences From a Survey Study of Adults With Arthrogryposis Multiplex Congenita. 疼痛与健康：来自成人多重先天性关节挛缩症调查研究的性别差异。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2026-08-05 DOI: 10.1002/ajmg.c.70021

Jaclyn Megan Sions, Maureen Donohoe, Claire Elizabeth Vallery, Samantha Jeanne Stauffer, Ryan Todd Pohlig

{"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":"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.","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}

引用次数: 0

Upper Extremity Entrapment Neuropathies in Adults With Arthrogryposis Multiplex Congenita: A National Database Study. 成人多发性先天性关节挛缩的上肢压迫性神经病：一项国家数据库研究。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2026-07-05 DOI: 10.1002/ajmg.c.70018

Adam Boukind, Andrea Biaggi-Ondina, Aidin R T Apte, Aneri U Patel, Amber R Leis

{"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":"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.","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}

引用次数: 0

Posthumously Diagnosed Myhre Syndrome Presenting With Pleural Remodeling and Endometrial Cancer. 死后诊断Myhre综合征，表现为胸膜重塑和子宫内膜癌。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2026-06-28 DOI: 10.1002/ajmg.c.70014

Jeanette Saffir, Karee Morgan, Karigynn Chaimson, Blake E Funke, Kim L Sandler, Melissa Hogan, Thomas Cassini

{"title":"Posthumously Diagnosed Myhre Syndrome Presenting With Pleural Remodeling and Endometrial Cancer.","authors":"Jeanette Saffir, Karee Morgan, Karigynn Chaimson, Blake E Funke, Kim L Sandler, Melissa Hogan, Thomas Cassini","doi":"10.1002/ajmg.c.70014","DOIUrl":"https://doi.org/10.1002/ajmg.c.70014","url":null,"abstract":"Myhre syndrome (OMIM 139210) is a genetic condition defined by neurodevelopmental disability, characteristic facial features, and multisystem proliferative fibrosis. While various types of lung disease have been reported, pleural remodeling leading to restrictive lung disease has not yet been described. There is also a possible increased risk of malignancy, although this is difficult to confirm given the rarity of the condition. A 43-year-old woman with short stature, intellectual disability, recent unintentional weight loss, and a uterine mass was admitted to the intensive care unit for respiratory failure. She had pleural effusions and the lungs did not expand following thoracentesis, consistent with a trapped lung. A uterine mass was also identified that was likely endometrioid carcinoma. In light of this, it was suspected that her lung disease was due to metastatic disease; however, pleural fluid studies did not show evidence of malignancy. Following her death, exome sequencing resulted and identified a pathogenic variant on SMAD4 (NM_005359.5:c.1498A>G (p.Ile500Val)), consistent with a diagnosis of Myhre syndrome. In retrospect, her lung disease was thought to be related to fibrothorax as a complication of Myhre syndrome. This case illustrates the breadth of fibrotic disease that can occur in individuals with Myhre syndrome by describing the first reported case of pleural remodeling leading to fibrothorax. Additionally, our patient's diagnosis of endometrial cancer strengthens the evidence for the proposed increased risk of malignancy in Myhre syndrome.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343746","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}

引用次数: 0

The International Consortium for Arthrogryposis: A Collaborative Framework for Early Detection, Care, Research, and Education. 国际关节挛缩症协会：早期检测、护理、研究和教育的合作框架。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2026-06-26 DOI: 10.1002/ajmg.c.70013

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

{"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":"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.","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}

引用次数: 0

Caring for Pediatric Clients With Arthrogryposis Multiplex Congenita: The Development of an Occupational Therapy Continuing Education Course. 照顾患有多重先天性关节挛缩症的儿童：职业治疗继续教育课程的发展。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2026-06-18 DOI: 10.1002/ajmg.c.70015

Amy Sitabkhan, April Cowan, Amy Boyd, Scott Oishi

{"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":"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.","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}

引用次数: 0

Apical Ectodermal Ridge Disruption and Hypoplastic Digits in Amyoplasia. 肌增生症的顶端外胚层嵴断裂和指发育不全。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2026-06-18 DOI: 10.1002/ajmg.c.70016

Amanda Stutman, Natalie Williams, Sarah Nossov, Dan Zlotolow

{"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":"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.","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}

引用次数: 0

Review of the Molecular and Developmental Basis of Myhre Syndrome, Bench Research. Myhre综合征的分子和发育基础综述，基础研究。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2026-06-10 DOI: 10.1002/ajmg.c.70010

Camille Viaut, Valerie Cormier-Daire

{"title":"Review of the Molecular and Developmental Basis of Myhre Syndrome, Bench Research.","authors":"Camille Viaut, Valerie Cormier-Daire","doi":"10.1002/ajmg.c.70010","DOIUrl":"10.1002/ajmg.c.70010","url":null,"abstract":"Myhre syndrome (MS) is a connective-tissue disorder within the acromelic dysplasia spectrum. It is characterized by congenital craniofacial, skeletal, cutaneous anomalies, respiratory, cardiovascular along with intellectual disability, deafness, and progressive fibrosis. MS is caused by germline variants in the transcriptional co-regulator SMAD4 (mothers against DPP homolog 4). SMAD4 is a key intracellular mediator of signal transduction and participates in several pathways, notably canonical TGFβ and BMP signaling. These pathways play central roles in developmental and homeostatic processes. As the number of reported MS cases continues to grow, clarifying its pathophysiology is becoming increasingly important. Current evidence suggests that dysregulation of TGFβ/BMP signaling contributes to extracellular matrix (ECM) disorganization and fibrosis in MS, a relationship that remains under active investigation. Here, we review the literature and summarize current knowledge on the clinical features and pathogenic mechanisms of MS. We also discuss emerging biological roles of molecular actors that appear to be compromised, and outline therapeutic strategies that may lead to promising interventions to improve patients' quality of life.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148209831","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}

引用次数: 0