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

{"title":"Invisible strings","authors":"Ariel Ellen Shaver Lee","doi":"10.1002/ajmg.c.32107","DOIUrl":"10.1002/ajmg.c.32107","url":null,"abstract":"","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 2-3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995094","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":"Direct-to-consumer genome sequencing helps a mother take her child's diagnostic odyssey into her own hands","authors":"Meghan N. Bartos, Anna C. E. Hurst, Caterina Abdala Villa","doi":"10.1002/ajmg.c.32108","DOIUrl":"10.1002/ajmg.c.32108","url":null,"abstract":"","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 2-3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995092","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":"Catatonia responsive to corticosteroids in a patient with an SCN2A variant","authors":"Kimberly Senko,&nbsp;Kelsey L. Saddoris,&nbsp;Ella Baus,&nbsp;Katherine Soe,&nbsp;Samuel E. Vaughn","doi":"10.1002/ajmg.c.32101","DOIUrl":"10.1002/ajmg.c.32101","url":null,"abstract":"<p>Variants in <i>SCN2A</i> are a known risk factor for developing autism spectrum disorder (ASD). Catatonia is a complex neuropsychiatric syndrome, which occurs at a higher rate in individuals with ASD. Catatonia has also been associated with COVID-19 infection, though the majority of these cases are associated with increased serum inflammatory markers. We present a case of a 15-year-old female with ASD and corticosteroid responsive stuporous catatonia to explore the relationship between <i>SCN2A</i> variants, ASD, COVID-19 exposure, and treatment refractory catatonia. Despite a lack of significantly elevated serum or CSF inflammatory markers, this patient showed significant improvement following initiation of corticosteroid therapy. This case presents a novel approach to the work-up and treatment of catatonia in individuals with <i>SCN2A</i> variants independent of elevated inflammatory markers.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756538","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}

{"title":"Expanding the phenotype of neurofibromatosis type 1 microdeletion syndrome","authors":"Jenny P. Garzon,&nbsp;Andrea Patete,&nbsp;Lindsey Aschbacher-Smith,&nbsp;Dima Qu'd,&nbsp;Geraldine Kelly-Mancuso,&nbsp;Carolyn R. Raski,&nbsp;Allison Goetsch Weisman,&nbsp;Madison Hankins,&nbsp;Michael Sawin,&nbsp;Katherine Kim,&nbsp;Andy Drackley,&nbsp;Janice Zeid,&nbsp;K. Nicole Weaver,&nbsp;Robert J. Hopkin,&nbsp;Howard M. Saal,&nbsp;Joel Charrow,&nbsp;Elizabeth Schorry,&nbsp;Robert Listernick,&nbsp;Brittany N. Simpson,&nbsp;Carlos E. Prada","doi":"10.1002/ajmg.c.32095","DOIUrl":"10.1002/ajmg.c.32095","url":null,"abstract":"<p>Neurofibromatosis type 1 (NF-1) microdeletion syndrome accounts for 5 to 11% of individuals with NF-1. The aim of our study was to characterize a large cohort of individuals with NF-1 microdeletion syndrome and expand its natural history. We conducted a retrospective chart review from 1994 to 2024 of individuals with NF-1 microdeletion syndrome followed at two large Neurofibromatosis Clinics. This cohort consists of 57 individuals with NF-1 microdeletion syndrome (28 type-1, 4 type-2, 2 type-3, 9 atypical deletions, and 14 indeterminate). We note 38/56 (67.9%) with describable facial features, 25/57 (43.8%) with plexiform neurofibromas, and 3/57 (5.2%) with malignant peripheral nerve sheath tumors within the observed period. The most reported neurodevelopmental manifestations from school-age or older individuals included 39/49 (79.6%) with developmental delays, 35/49 (71.4%) with expressive and/or receptive speech delays, 33/41 (80.5%) with learning difficulties, and 23/42 (54.8%) with attention-deficit/hyperactivity disorder. Full-scale IQ testing data was available for 22 individuals (range: 50–96). Of the 21 adults in this cohort, 14/21 (66.7%) graduated from high school, and 4/21 (19.0%) had some college experience. Many individuals received academic support (i.e., special education, individual education plan). In this cohort, neurocognitive outcomes in adults varied more than typically reported in the literature.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632407","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}

{"title":"Negative, normal, nondiagnostic","authors":"Arthur Lenahan","doi":"10.1002/ajmg.c.32100","DOIUrl":"10.1002/ajmg.c.32100","url":null,"abstract":"","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 2-3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632408","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":"Multiorgan manifestations of COL4A1 and COL4A2 variants and proposal for a clinical management protocol","authors":"Simone Gasparini,&nbsp;Simona Balestrini,&nbsp;Luigi Francesco Saccaro,&nbsp;Giacomo Bacci,&nbsp;Giorgia Panichella,&nbsp;Martino Montomoli,&nbsp;Gaetano Cantalupo,&nbsp;Stefania Bigoni,&nbsp;Giorgia Mancano,&nbsp;Simona Pellacani,&nbsp;Vincenzo Leuzzi,&nbsp;Nila Volpi,&nbsp;Francesco Mari,&nbsp;Federico Melani,&nbsp;Mara Cavallin,&nbsp;Tiziana Pisano,&nbsp;Giulio Porcedda,&nbsp;Augusto Vaglio,&nbsp;Davide Mei,&nbsp;Carmen Barba,&nbsp;Elena Parrini,&nbsp;Renzo Guerrini","doi":"10.1002/ajmg.c.32099","DOIUrl":"10.1002/ajmg.c.32099","url":null,"abstract":"<p><i>COL4A1/2</i> variants are associated with highly variable multiorgan manifestations. Depicting the whole clinical spectrum of <i>COL4A1/2</i>-related manifestations is challenging, and there is no consensus on management and preventative strategies. Based on a systematic review of current evidence on <i>COL4A1/2</i>-related disease, we developed a clinical questionnaire that we administered to 43 individuals from 23 distinct families carrying pathogenic variants. In this cohort, we extended ophthalmological and cardiological examinations to asymptomatic individuals and those with only limited or mild, often nonspecific, clinical signs commonly occurring in the general population (i.e., oligosymptomatic). The most frequent clinical findings emerging from both the literature review and the questionnaire included stroke (203/685, 29.6%), seizures or epilepsy (199/685, 29.0%), intellectual disability or developmental delay (168/685, 24.5%), porencephaly/schizencephaly (168/685, 24.5%), motor impairment (162/685, 23.6%), cataract (124/685, 18.1%), hematuria (63/685, 9.2%), and retinal arterial tortuosity (58/685, 8.5%). In oligosymptomatic and asymptomatic carriers, ophthalmological investigations detected retinal vascular tortuosity (5/13, 38.5%), dysgenesis of the anterior segment (4/13, 30.8%), and cataract (2/13, 15.4%), while cardiological investigations were unremarkable except for mild ascending aortic ectasia in 1/8 (12.5%). Our multimodal approach confirms highly variable penetrance and expressivity in <i>COL4A1/2</i>-related conditions, even at the intrafamilial level with neurological involvement being the most frequent and severe finding in both children and adults. We propose a protocol for prevention and management based on individualized risk estimation and periodic multiorgan evaluations.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625676","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}

{"title":"Practicalities (and real-life experiences) of dementia in adults with Down syndrome","authors":"Ayesha Harisinghani,&nbsp;Clorinda Cottrell,&nbsp;Karen Donelan,&nbsp;Alice D. Lam,&nbsp;Margaret Pulsifer,&nbsp;Stephanie L. Santoro","doi":"10.1002/ajmg.c.32098","DOIUrl":"10.1002/ajmg.c.32098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Adults with down syndrome (DS) have a lifetime dementia risk in excess of 95%, with a median age of onset of 55 years, due to trisomy 21. Co-occurring Alzheimer's disease (AD) has increased morbidity and mortality, and it is now recommended to screen for AD in all adults with DS beginning at 40 years of age. In this manuscript, we present two clinical cases of adults with DS who developed AD summarizing their medical histories, presenting symptoms, path to diagnosis and psychosocial aspects of care collected from retrospective chart review with caregiver consent. These two cases were chosen due to their complexity and interwoven nature of the medical and psychosocial aspects, and highlight the complexity and nuance of caring for patients with DS and AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533337","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":"On stillness","authors":"Linda Z. Rossetti","doi":"10.1002/ajmg.c.32096","DOIUrl":"10.1002/ajmg.c.32096","url":null,"abstract":"&lt;p&gt;When I was a resident, in one of the largest medical centers in the world, any day I was on inpatient consult service would be a day I exceeded my step goal. Without fail. I'd arrive to the fellows' office early in the morning, spend the next 10–12 h traipsing around multiple different buildings—the children's hospital, the women's hospital, the adult hospital, the other women's hospital, the medical school—before exhaustedly making my way back to the fellows' office to pack up my things, head home to get some precious sleep, then wake up before the sun to do it all over again. Constantly moving, constantly on the go. On consult service as a trainee, my internal pistons fired ceaselessly. Now, as an attending at a different health system, the geographic surface area I cover walking to see consults may be less, but the low-level buzzing in my chest whenever I'm on call persists, and the routine remains the same. I get paged, review the chart, go see the patient, call the team, order testing, write the note, rinse, and repeat.&lt;/p&gt;&lt;p&gt;Not long ago, during one of my call weeks, my phone pinged with the unique alert I assigned to our hospital system's internal paging app. A new consult, this time from the pediatric intensive care unit, from which many of our consults originate. I scanned the information provided as my brain began whirring, trying to read, process, and act all at the same time. &lt;i&gt;Baby. Very sick baby. Unclear reason for decompensation. Parents at bedside. Probably needs broad testing with parental samples&lt;/i&gt;. As I looked through the chart, gathering background information, I was simultaneously pulling paperwork and educational materials from my desk drawers in preparation for my discussion with the family.&lt;/p&gt;&lt;p&gt;At my next break between clinic patients, I briskly walked from my office in the outpatient clinic building, across the big blue skybridge often used as a can't-miss-it landmark on the medical campus, into the main children's hospital. I hopped in the elevator and pressed the button for the ICU, still mentally running through my growing checklist of tasks.&lt;/p&gt;&lt;p&gt;When I arrived in front of the correct room, double checking the notes I had scrawled onto a sticky note to confirm, I noticed that this patient had been already been admitted long enough for the nursing staff and child life specialists to have helped his family create a colorful decorative nametag for his door and tape photographs of his cheery face from better times in the skinny window. I took half of a second to look at each photo. It helped ground me in the context of the conversation I was about to have with a worried, hurting, possibly traumatized family. A conversation that I'd had many times before and would have many times to come. Even if you're not the sickest person in the hospital, no one is getting a genetics consult on the best day of their life. A customary knock, then I stepped into the room.&lt;/p&gt;&lt;p&gt;The baby appeared far too small to be laying in a ","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 2-3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465475","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}

{"title":"Occurrence of mosaic Down syndrome and prevalence of co-occurring conditions in Medicaid enrolled adults, 2016–2019","authors":"Eric Rubenstein,&nbsp;Salina Tewolde,&nbsp;Brian G. Skotko,&nbsp;Amy Michals,&nbsp;Juan Fortea","doi":"10.1002/ajmg.c.32097","DOIUrl":"10.1002/ajmg.c.32097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mosaic Down syndrome is a triplication of chromosome 21 in some but not all cells. Little is known about the epidemiology of mosaic Down syndrome. We described prevalence of mosaic Down syndrome and the co-occurrence of common chronic conditions in 94,533 Medicaid enrolled adults with any Down syndrome enrolled from 2016 to 2019.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified mosaic Down syndrome using the International Classification of Diseases and Related Health Problems, tenth edition code for mosaic Down syndrome and compared to those with nonmosaic Down syndrome codes. We identified chronic conditions using established algorithms and compared prevalence by mosaicism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 1966 (2.08%) had claims for mosaic Down syndrome. Mosaicism did not differ by sex or race/ethnicity with similar age distributions. Individuals with mosaicism were more likely to present with autism (13.9% vs. 9.6%) and attention deficit hyperactivity disorder (17.7% vs. 14.0%) compared to individuals without mosaicism. In total, 22.3% of those with mosaic Down syndrome and 21.5% of those without mosaicism had claims for Alzheimer's dementia (Prevalence difference: 0.8; 95% Confidence interval: −1.0, 2.8). The mosaic group had 1.19 times the hazard of Alzheimer's dementia compared to the nonmosaic group (95% CI: 1.0, 1.3).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Mosaicism may be associated with a higher susceptibility to certain neurodevelopmental and neurodegenerative conditions, including Alzheimer's dementia. Our findings challenge previous assumptions about its protective effects in Down syndrome. Further research is necessary to explore these associations in greater depth.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454522","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 plot TWIST","authors":"Sophia R. Meyer,&nbsp;Tara L. Wenger","doi":"10.1002/ajmg.c.32090","DOIUrl":"10.1002/ajmg.c.32090","url":null,"abstract":"","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 2-3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417213","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}