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

{"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}

{"title":"Blepharophimosis with intellectual disability and Helsmoortel-Van Der Aa Syndrome share episignature and phenotype","authors":"Camilla Sarli,&nbsp;Liselot van der Laan,&nbsp;Jack Reilly,&nbsp;Slavica Trajkova,&nbsp;Diana Carli,&nbsp;Alfredo Brusco,&nbsp;Michael A. Levy,&nbsp;Raissa Relator,&nbsp;Jennifer Kerkhof,&nbsp;Haley McConkey,&nbsp;Matthew L. Tedder,&nbsp;Cindy Skinner,&nbsp;Mariëlle Alders,&nbsp;Peter Henneman,&nbsp;Raoul C. M. Hennekam,&nbsp;Claudia Ciaccio,&nbsp;Stefano D'Arrigo,&nbsp;Antonio Vitobello,&nbsp;Laurence Faivre,&nbsp;Sacha Weber,&nbsp;Aline Vincent-Devulder,&nbsp;Laurence Perrin,&nbsp;Alexia Bourgois,&nbsp;Toshiyuki Yamamoto,&nbsp;Kay Metcalfe,&nbsp;Marcella Zollino,&nbsp;Usha Kini,&nbsp;Daniela Oliveira,&nbsp;Sergio B. Sousa,&nbsp;Denise Williams,&nbsp;Gerarda Cappuccio,&nbsp;Bekim Sadikovic,&nbsp;Nicola Brunetti-Pierri","doi":"10.1002/ajmg.c.32089","DOIUrl":"10.1002/ajmg.c.32089","url":null,"abstract":"<p>Blepharophimosis with intellectual disability (BIS) is a recently recognized disorder distinct from Nicolaides-Baraister syndrome that presents with distinct facial features of blepharophimosis, developmental delay, and intellectual disability. BIS is caused by pathogenic variants in <i>SMARCA2</i>, that encodes the catalytic subunit of the superfamily II helicase group of the BRG1 and BRM-associated factors (BAF) forming the BAF complex, a chromatin remodeling complex involved in transcriptional regulation. Individuals bearing variants within the bipartite nuclear localization (BNL) signal domain of <i>ADNP</i> present with the neurodevelopmental disorder known as Helsmoortel-Van Der Aa Syndrome (HVDAS). Distinct DNA methylation profiles referred to as episignatures have been reported in HVDAS and BAF complex disorders. Due to molecular interactions between <i>ADNP</i> and BAF complex, and an overlapping craniofacial phenotype with narrowing of the palpebral fissures in a subset of patients with HVDAS and BIS, we hypothesized the possibility of a common phenotype-specific episignature. A distinct episignature was shared by 15 individuals with BIS-causing <i>SMARCA2</i> pathogenic variants and 12 individuals with class II HVDAS caused by truncating pathogenic <i>ADNP</i> variants. This represents first evidence of a sensitive phenotype-specific episignature biomarker shared across distinct genetic conditions that also exhibit unique gene-specific episignatures.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330198","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":"Simpson–Golabi–Behmel syndrome","authors":"Alessandro Vaisfeld,&nbsp;Giovanni Neri","doi":"10.1002/ajmg.c.32088","DOIUrl":"10.1002/ajmg.c.32088","url":null,"abstract":"<p>The Simpson–Golabi–Behmel syndrome (SGBS; OMIM 312870) is an overgrowth/multiple congenital anomalies/dysplasia condition, inherited as an X-linked semi-dominant trait, with variable expressivity in males and reduced penetrance and expressivity in females. The clinical spectrum is broad, ranging from mild manifestations in both males and females to multiple malformations and neonatal death in the more severely affected cases. An increased risk of neoplasia is reported, requiring periodical surveillance. Intellectual development is normal in most cases. SGBS is caused by a loss-of-function mutation of the <i>GPC3</i> gene, either deletions or point mutations, distributed all over the gene. Notably, <i>GPC3</i> deletion/point mutations are not found in a significant proportion of clinically diagnosed SGBS cases. The protein product GPC3 is a glypican functioning as a receptor for Hh at the cell surface, involved in the Hh-Ptc-Smo signaling pathway, a regulator of cellular growth.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064827","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":"Investigations of an individual with a Marfanoid habitus, mild intellectual disability, and severe social anxiety identifies PCDHGA5 as a candidate neurodevelopmental disorder gene","authors":"Henri Margot,&nbsp;Adrien Pizano,&nbsp;Anouck Amestoy,&nbsp;Didier Lacombe,&nbsp;Camille Berges,&nbsp;Claire Beneteau,&nbsp;A. Micheil Innes","doi":"10.1002/ajmg.c.32087","DOIUrl":"10.1002/ajmg.c.32087","url":null,"abstract":"<p>Marfanoid habitus and intellectual disability (MHID) co-occur in multiple neurodevelopmental disorders (NDD). Among those, Lujan-Fryns, an X-linked genetic disorder associated with variants in <i>MED12</i> was the first such syndrome identified. Accurate molecular diagnosis for these MHID syndromes remains a challenge due to significant clinical and genetic heterogeneity. We present a case report of a 20-year-old male patient with MHID and severe social anxiety. A comprehensive clinical evaluation, including morphotype assessment, cognitive, and psychometric and genetic testing, was conducted to provide a detailed understanding of the patient's complex clinical presentation. Psychometric assessments revealed severe social anxiety and various cognitive and emotional challenges. Despite some autism-like symptoms, the patient's clinical presentation was more aligned with mild intellectual disability. Exome sequencing was inconclusive but identified a heterozygous de novo missense variant in the <i>PCDHGA5</i> gene. This gene is not known in human pathology yet, but we also report a second patient with a syndromic neurodevelopmental disorder and a rare de novo variant which leads us to propose this as a candidate gene. Our findings emphasize the importance of multidisciplinary approach in the diagnosis and management of MHID. This case report underscores the need for objective clinical evaluations and standardized tools to better understand the complex clinical profiles of patients with NDDs. The identification of novel <i>PCDHGA5</i> gene variants adds this gene's candidacy to the genetic landscape of MHID-NDD, warranting further investigation to determine its potential contribution.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140583215","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":"The dream of a diagnosis","authors":"Golda Grinberg","doi":"10.1002/ajmg.c.32086","DOIUrl":"10.1002/ajmg.c.32086","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":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140583210","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":"Domain-specific phenotypes in LINS1-related disorder—A Chinese family with the Q92X variant and literature review","authors":"Xu-Ying Li,&nbsp;Zhanjun Wang,&nbsp;Yanping Yang,&nbsp;Ruichai Lin,&nbsp;Chaodong Wang","doi":"10.1002/ajmg.c.32085","DOIUrl":"10.1002/ajmg.c.32085","url":null,"abstract":"<p><i>LINS1</i> is the human homolog of the Drosophila segment polarity gene that encodes an essential regulator of the wingless/Wnt signaling. By 2011, only seven pedigrees (16 patients) with eight causative variants in <i>LINS1</i> gene have been reported. These cases mainly presented with infancy-/child-onset neurodevelopmental disorders, facial dysmorphia, and other clinical features, and a wide spectrum of clinically distinct phenotypes were also manifested. In our study, two brothers in a family were admitted and diagnosed with child-onset movement disorders, slight intellectual disability, psychological symptoms, eye problems, urinary and bowel dysfunction, mitral value prolapse, and Q-T prolongation. By exome sequencing, we identified a nonsense homozygous pathogenic variant (<i>LINS1</i>: c.274C &gt; T (p.Q92X)), which had been reported in a case diagnosed with intellectual disability and psychiatric disorders (such as schizophrenia and anxiety). Compared with this case, the clinical features of our cases were distinct. In particular, our cases displayed unusual features of heart and blood system. Furthermore, the genotype–phenotype relationship analysis suggested that distinct phenotypes presented in cases carrying variants in different domains of the <i>LINS1</i> gene. In conclusions, our findings suggest the high clinical variations in the <i>LINS1</i> variants-related disorders. Moreover, the Q92X might be a recurrent variant in Hans of Southern China.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334340","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":"Cover Image, Volume 196, Number 1, March 2024","authors":"","doi":"10.1002/ajmg.c.32084","DOIUrl":"https://doi.org/10.1002/ajmg.c.32084","url":null,"abstract":"<p><b>Cover legend: Photo credit: Andy Meredith, man with Down syndrome. Andy Meredith Photography,</b> https://andymeredith.com\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140104495","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}