American Journal of Medical Genetics Part C: Seminars in Medical Genetics最新文献_第3页

Journaling for Parents and Adults With Myhre Syndrome: Using Reflective Writing to Help Cope. 为患有迈尔综合征的父母和成年人写日记：使用反思性写作来帮助应对。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-12-01 Epub Date: 2025-07-20 DOI: 10.1002/ajmg.c.32147

Rachel Gottlieb, Ashley W Wong, Allison L Cirino, Eleanor R Scimone, Angela E Lin

{"title":"Journaling for Parents and Adults With Myhre Syndrome: Using Reflective Writing to Help Cope.","authors":"Rachel Gottlieb, Ashley W Wong, Allison L Cirino, Eleanor R Scimone, Angela E Lin","doi":"10.1002/ajmg.c.32147","DOIUrl":"10.1002/ajmg.c.32147","url":null,"abstract":"Myhre syndrome is a rare progressive genetic disorder characterized by hearing loss, cardiovascular and joint problems, neoplasia, and neuropsychologic disabilities. Parents of children with Myhre syndrome and adults themselves face unique challenges, stresses, and fears associated with this diagnosis. Reflective writing in the form of journaling can provide psychosocial support and help individuals cope with this diagnosis. Adult patients and parents whose children were evaluated at the Massachusetts General Hospital Myhre Syndrome Clinic were invited to participate in a three-month journaling intervention. Participation in the study required the completion of a series of surveys prior to starting and upon completion of the study. Data from these surveys were analyzed to assess for change in mental well-being. Eleven individuals participated, six of whom completed the three-month journaling intervention and post-journaling surveys. Three participants indicated that journaling had an impact on their mental well-being, and of these, two planned to continue journaling. However, there was no statistically significant difference in mental well-being scores pre- and post-journaling intervention. The very small size of the study limits interpretation, but we think it is reasonable to suggest that expressive writing through journaling may be a coping mechanism and means of improving well-being for some individuals in the Myhre syndrome community.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"269-274"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673733","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

Autosomal Dominant Transmission Reframes Reproductive Counseling in Myhre Syndrome: A Novel Family and Literature Review. 常染色体显性遗传重塑Myhre综合征的生殖咨询：一个新家族和文献综述。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-12-01 Epub Date: 2025-12-07 DOI: 10.1002/ajmg.c.32161

Maggie R Brand, Eva Vanbelleghem, Alison C Kay, Anne Goriely, Senol Demir, Peter J Hulick, Breanne Prindeville, Ashley W Wong, Bert Callewaert, Angela E Lin

{"title":"Autosomal Dominant Transmission Reframes Reproductive Counseling in Myhre Syndrome: A Novel Family and Literature Review.","authors":"Maggie R Brand, Eva Vanbelleghem, Alison C Kay, Anne Goriely, Senol Demir, Peter J Hulick, Breanne Prindeville, Ashley W Wong, Bert Callewaert, Angela E Lin","doi":"10.1002/ajmg.c.32161","DOIUrl":"10.1002/ajmg.c.32161","url":null,"abstract":"Myhre syndrome is a rare disorder that typically results from a de novo SMAD4 variant. De novo SMAD4 variants have recently been shown to be associated with 'selfish selection' in the male germline, explaining their exclusive paternal origin and the paternal age effect reported for Myhre syndrome. Over recent years, there has been a steady increase in the number of families reported with an affected parent and child. We expand the literature of families with Myhre syndrome reporting a mildly affected 38-year-old mother and her 4-year-old son who carry the SMAD4 p.Arg496Cys variant, consistent with all other reports of inherited Myhre syndrome. To better delineate the phenotypic spectrum, we developed a clinical severity score and compared familial cases to sporadic cases, revealing a milder phenotype in familial cases. Affected mothers with Myhre syndrome may be at increased risk of infertility and pregnancy loss. Since identification of the mode of transmission is essential for accurate reproductive counseling and appropriate clinical surveillance, we propose a nuanced reproductive and genetic counseling strategy that emphasizes awareness of potential autosomal dominant transmission, paternal age-related risk, and obstetric complications.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"330-343"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699518","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

Therapy for Myhre Syndrome: Goals, Misconceptions, and Current Agents. Myhre综合征的治疗：目标、误解和当前的药物。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-12-01 Epub Date: 2026-03-16 DOI: 10.1002/ajmg.c.70008

Alessandro De Falco, Alfonso Manuel D'Alessio, Nicola Brunetti-Pierri

{"title":"Therapy for Myhre Syndrome: Goals, Misconceptions, and Current Agents.","authors":"Alessandro De Falco, Alfonso Manuel D'Alessio, Nicola Brunetti-Pierri","doi":"10.1002/ajmg.c.70008","DOIUrl":"10.1002/ajmg.c.70008","url":null,"abstract":"Myhre Syndrome (MYHRS, MIM #139210) is a rare, multisystem connective tissue disorder caused by recurrent heterozygous gain-of-function pathogenic variants in the SMAD4 gene, a key player in TGF-β signaling and a regulator of extracellular matrix homeostasis. MYHRS is characterized by a progressive fibrotic phenotype affecting multiple organ systems, including the skeletal, cardiovascular, respiratory, and integumentary systems. MYHRS individuals often present with short stature, joint contractures, cardiac valve defects, subglottic stenosis, and skin thickening. Neurodevelopmental disorders, including autism spectrum disorder, may also occur. Despite the recurrent mutations, MYHRS individuals have significant phenotypic variability. Treatment for MYHRS is symptomatic, and no disease-modifying therapies are currently available. In this article, we discuss potential future therapies in MYHRS, such as TGF-β inhibitors, anti-fibrotic drugs, and gene editing approaches. Furthermore, we discuss unmet needs on clinical and biochemical endpoints that are critical for the investigation of new therapies.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"386-391"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462366","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

Navigating Drug Discovery for Myhre Syndrome: The Complexity of a Multisystemic Rare Disease. Myhre综合征的药物发现导航：多系统罕见疾病的复杂性。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-12-01 Epub Date: 2025-11-03 DOI: 10.1002/ajmg.c.32156

Armelle Pindon, Nicola Brunetti-Pierri, Kathy H Young, Mary K Young, Maria J Macias, Xiulei Mo

{"title":"Navigating Drug Discovery for Myhre Syndrome: The Complexity of a Multisystemic Rare Disease.","authors":"Armelle Pindon, Nicola Brunetti-Pierri, Kathy H Young, Mary K Young, Maria J Macias, Xiulei Mo","doi":"10.1002/ajmg.c.32156","DOIUrl":"10.1002/ajmg.c.32156","url":null,"abstract":"Myhre syndrome is a rare, multisystemic disorder caused by gain-of-function mutations in the SMAD4 gene, a key component of the TGF-β signaling pathway. These mutations lead to manifestations affecting neurodevelopment, bone and joint development, fibrosis and stenosis, immune responses, reproductive health, and cardiac function. The Myhre Syndrome Foundation (MSF) is a patient-centered organization focused on accelerating drug discovery while supporting patients, prioritizing research targeting fibrosis/stenosis and autism/intellectual and developmental disabilities, the most significant burdens reported by patients. Their short-term strategy involves: (1) Creating and running a preclinical platform to screen potential treatments using patient-derived and animal models. (2) Clinical readiness, addressing challenges associated with low disease incidence and heterogeneity in clinical trial design, by developing multi-domain endpoints, responder index, and biobanks/biomarkers. (3) Target identification investigating SMAD4 pathogenic variants rewiring protein-protein interactions in key signaling pathways. (4) Fostering partnerships with regulatory authorities, industries, and other patient research organizations. The MSF portfolio includes targeting fibrosis with immunotherapy using FAP-CAR-T cells, and a precision medicine approach aimed at restoring normal SMAD4 function through gene editing and small molecules. MSF aims to develop therapies that address both acute and chronic manifestations of this complex disease, improving the quality of life for affected individuals.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"290-305"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13454938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spectrum of Congenital Anomalies in Myhre Syndrome-Insights Into Effects Brought by Altered TGF-β Signaling via Gain-of-Function Variants in SMAD4. Myhre综合征先天性异常的频谱- TGF-β信号改变通过SMAD4的功能获得变体带来的影响的见解

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-12-01 Epub Date: 2026-04-13 DOI: 10.1002/ajmg.c.70007

Kawmadi Gunawardena, Alessandro De Falco, Deborah Osio, Eleanor Sherlock, Emma Kivuva, Erina Sasaki, Francis H Sansbury, Nayana Lahiri, Patricia Foley, Sahar Mansour, Shane McKee, Tazeen Ashraf, Nicola Brunetti-Pierri, Usha Kini

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 : 2025-12-01 Epub 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":"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":"379-385"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","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

Psychotic Features in Myhre Syndrome: Evidence for Broader Neuropsychiatric Surveillance. Myhre综合征的精神病特征：更广泛的神经精神监测的证据。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-12-01 Epub Date: 2026-06-10 DOI: 10.1002/ajmg.c.70011

Mariz Ebuen, Vasudevan Krishnan, Kathleen Irby, Ryan Monsberger, Rob J Hopkin, Maggie R Brand, Nora Friedman, Robyn P Thom, Allan L Reiss, Claudia Algaze, Jonathan A Bernstein, Samantha Alexander, Valerie Cormier-Daire, Angela E Lin, Suha Bachir

{"title":"Psychotic Features in Myhre Syndrome: Evidence for Broader Neuropsychiatric Surveillance.","authors":"Mariz Ebuen, Vasudevan Krishnan, Kathleen Irby, Ryan Monsberger, Rob J Hopkin, Maggie R Brand, Nora Friedman, Robyn P Thom, Allan L Reiss, Claudia Algaze, Jonathan A Bernstein, Samantha Alexander, Valerie Cormier-Daire, Angela E Lin, Suha Bachir","doi":"10.1002/ajmg.c.70011","DOIUrl":"10.1002/ajmg.c.70011","url":null,"abstract":"Myhre syndrome is a rare genetic disorder caused by pathogenic variants in SMAD4. The neurocognitive profile may include intellectual disability and developmental delay across a wide spectrum of domains. Four individuals with Myhre syndrome and psychosis and/or schizophrenia have been reported. We discuss three additional individuals (one briefly mentioned in a review of patients with Myhre syndrome) with SMAD4 pathogenic variants at codon Arg496Cys (two cases) and codon Ile500Val (one case). All had social challenges and variable developmental delays. They presented with acute-onset psychosis and were diagnosed with either psychosis, not otherwise specified, or psychosis associated with bipolar disorder. The seven individuals (5 female, 2 male) ranged in age from 13 to 24 years (mean 18.7 years) and had variable responses to pharmacologic and behavioral interventions. The underlying mechanism of psychosis in Myhre syndrome may be due to disruptions in the TGF-β signaling pathway, which involves the interactions of TGF-β family members and SMAD proteins, including SMAD4. Although additional cases are needed to verify our observations, psychosis may be a component of the neurodevelopmental phenotype of Myhre syndrome, highlighting the importance of rapid psychiatric evaluation and intervention.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"371-378"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148209836","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

Evaluation of the Mid and Lower Face in Three Females With Myhre Syndrome: Objective Methods to Supplement Subjective Assessment. 3例女性Myhre综合征中、下面部评价：主观评价的客观补充。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-12-01 Epub Date: 2025-11-21 DOI: 10.1002/ajmg.c.32160

Mohammad Mousavian, Maggie Brand, Angela E Lin, Zachary S Peacock

{"title":"Evaluation of the Mid and Lower Face in Three Females With Myhre Syndrome: Objective Methods to Supplement Subjective Assessment.","authors":"Mohammad Mousavian, Maggie Brand, Angela E Lin, Zachary S Peacock","doi":"10.1002/ajmg.c.32160","DOIUrl":"10.1002/ajmg.c.32160","url":null,"abstract":"Myhre syndrome is associated with a recognizable pattern of facial differences that develop after early childhood. Patients typically have midface hypoplasia, mandibular prognathism, narrow oral commissures with a short philtrum and thin upper lip vermillion. Other characteristics include deeply set eyes with short palpebral fissures, and small, widely spaced teeth. The aim of this study is to review the concept of prognathism in Myhre syndrome, describe the oral and maxillofacial surgery (OMS) evaluation of three females, and provide some preliminary data to propose more objective guidelines and diagnostic tools for facial evaluation in other patients. In addition to the dysmorphologic examination, maxillofacial imaging is recommended in many patients to evaluate the dentition, midface and mandibular anatomy. An orthopantomogram is useful to visualize the dentition, alveolar portion of the maxilla and the mandible. A lateral cephalogram can assess jaw relationships and allow cephalometric analyses to compare to published norms. With the common characteristics visualized, a checklist has been developed to serve as a guide when evaluating patients. OMS consultation can enhance the care provided by the medical geneticists who usually manage these individuals.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"306-312"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572885","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

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 : 2025-12-01 Epub Date: 2026-08-31 DOI: 10.1002/ajmg.c.70022

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

引用次数: 0

The Diagnosis That Arrived Decades Late: Living Without and Then With Myhre Syndrome. 姗姗来迟的诊断：没有梅尔综合征的生活，然后又有了梅尔综合征。

IF 2.5 3区医学

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Pub Date : 2025-12-01 Epub Date: 2025-08-14 DOI: 10.1002/ajmg.c.32149

Abdallah F Elias

{"title":"The Diagnosis That Arrived Decades Late: Living Without and Then With Myhre Syndrome.","authors":"Abdallah F Elias","doi":"10.1002/ajmg.c.32149","DOIUrl":"10.1002/ajmg.c.32149","url":null,"abstract":"Myhre syndrome (MIM #139210) is a rare multisystem disorder first described in 1981, characterized by short stature, neurodevelopmental delay, joint contractures, and cardiopulmonary complications. Its molecular basis, recurrent pathogenic variants in SMAD4, was not discovered until 2011. This narrative is based on a review of medical records, personal experiences in the care of a remarkable patient, and family interviews. It traces the life of a young man from rural Montana whose diagnosis was delayed for over two decades, despite early evaluations by renowned specialists. The absence of a unifying diagnosis profoundly shaped his and his family's experience-emotionally, medically, and socially. When the diagnosis of Myhre syndrome was finally established via whole exome sequencing in adulthood, it brought both clarity and new uncertainties. Through his story, we examine the psychosocial toll of diagnostic delay, the transformative potential of genomic medicine, and the resilience of individuals and families living with complex, undiagnosed conditions. The narrative also underscores the ongoing systemic barriers to care and inclusion for individuals with lifelong rare disorders. Lastly, this account offers a reflection on the philosophical framework of Maurice Merleau-Ponty, whose phenomenology of the lived body versus the body-object provides a lens to understand the subjective and embodied dimensions of living with an undiagnosed condition.","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":" ","pages":"275-280"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844062","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