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

{"title":"Family Lore, a Variant of Uncertain Significance, and CADASIL","authors":"Rhys Duarte,&nbsp;Liesbeth Vossaert,&nbsp;Sandra A. Darilek,&nbsp;Chelsi Rose,&nbsp;Evan Schauer,&nbsp;Christian Parobek,&nbsp;Emily Bland,&nbsp;Keren Machol,&nbsp;Elizabeth Mizerik,&nbsp;Chaya N. Murali","doi":"10.1002/ajmg.c.32117","DOIUrl":"10.1002/ajmg.c.32117","url":null,"abstract":"<div>\u0000 \u0000 <p>An infant presents in extremis. After the medical team stabilizes him, the race is on to figure out why he got so sick in the first place. The consulting genetics team thinks that it is unlikely his problems are due to a genetic cause, but his extreme, confounding presentation is enough to justify trio exome sequencing. When the results reveal an unexpected, paternally inherited variant of uncertain significance (VUS) in <i>NOTCH3</i>, fresh questions arise. The infant's presenting symptoms and descriptive diagnoses, including hematemesis, epistaxis, and gastric ulcers, certainly do not fit the mold of CADASIL. However, closer inspection of his family history yields tantalizing clues: a father and paternal grandfather with seizures, and a paternal grandfather with unexplained mood disturbances in middle age. Combining details gleaned from the family history and medical literature, the clinical genetics and laboratory genetics team collaborated, reclassified the VUS as likely pathogenic, and offered a new unifying diagnosis to explain much of the family's lore.</p>\u0000 </div>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 2-3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455795","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 Rorschach Test","authors":"Oana Caluseriu","doi":"10.1002/ajmg.c.32116","DOIUrl":"10.1002/ajmg.c.32116","url":null,"abstract":"<p>Unexpectedly intersecting her path with a person with a congenital anomaly gives the writer an opportunity to reflect on her own understanding of patients outside the medical perimeter that ultimately influences her point of view during the hospital encounter.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 2-3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387237","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 Myhre Syndrome Foundation as a global modern support group: The business of rare","authors":"Kate Wears,&nbsp;Angela E. Lin,&nbsp;Lois J. Starr","doi":"10.1002/ajmg.c.32104","DOIUrl":"10.1002/ajmg.c.32104","url":null,"abstract":"<p>Advocacy support groups grow into national and international organizations, but they all begin with personal experiences. As the parents to a newly diagnosed two-year-old son with Myhre syndrome, my husband and I were overwhelmed with the journey ahead. Thanks to networking, primarily through social media, we located other families living with Myhre syndrome and were quickly immersed in the challenges and joy of this community. Myhre syndrome, caused by pathogenic missense variants in <i>SMAD4</i>, is a rare connective tissue disease characterized by short stature, hearing loss, neurodevelopmental challenges, and fibroproliferation. This personal essay, written with physician partners, describes the development of a global advocacy group for patients with Myhre syndrome. I have the honor of serving as the founding Executive Director and reflect proudly on the great strides that our marvelous support group has made. We empower the global community impacted by this rare condition by providing meaningful and accessible data, educational opportunities, and connections with others going through similar experiences. Utilizing the expertise of our Board of Directors and my corporate expertise, we discuss how we have been able to elevate our ultra-rare community into a broader, more comprehensive network.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339187","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":"Perspectives and Insights Into Phenylketonuria: Patient Narratives About the Early Years Following Newborn Screening","authors":"Brittany M. Holmes,&nbsp;Suzanne Hollander,&nbsp;Stephanie Sacharow","doi":"10.1002/ajmg.c.32110","DOIUrl":"10.1002/ajmg.c.32110","url":null,"abstract":"<p>Newborn screening for Phenylketonuria (PKU) began in 1963, and since then knowledge and treatment recommendations have evolved. In the decades following newborn screening for PKU, individual and family experiences varied widely. We present narratives by people living with PKU during these years, including individuals actively following in PKU clinic and those who have been out of PKU clinic for many years. These stories describe different individual experiences, including diet discontinuation in childhood, changing treatment guidelines, and new treatments that have become available.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 2-3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263455","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":"Ode to Fiona: The Face of Fortitude in FBXL4 Deficiency","authors":"Amanda Barone Pritchard","doi":"10.1002/ajmg.c.32115","DOIUrl":"10.1002/ajmg.c.32115","url":null,"abstract":"&lt;p&gt;There are some moments in medicine that stay with you forever—putting on your white coat as a medical student for the first time, experiencing the sorrow of disclosing a terminal diagnosis, and the joy of seeing a newborn in her mother's arms after delivery. One of those indelible moments for me is the moment Fiona took her last breath, and experiencing her mother's pain as if it were something tangible in the room.&lt;/p&gt;&lt;p&gt;I met Fiona when she was just 4 months old, when she was intubated and sedated in the PICU in the throes of influenza. I noticed how small she was; her little hands laid inert at her sides. She was more sick than typical, even for influenza, with a lactate level amongst the highest I had ever seen. I did not know what her diagnosis would be, but I worried it was not going to be good.&lt;/p&gt;&lt;p&gt;A few days after I met her, we had our answer for why Fiona was so ill. She had two pathogenic variants in &lt;i&gt;FBXL4&lt;/i&gt;—consistent with &lt;i&gt;FBXL4&lt;/i&gt;-related encephalomyopathic mitochondrial DNA depletion syndrome. We corralled the PICU team and her parents for a meeting. In an austere PICU conference room, we laid out the news. In retrospect, it was one of the last family meetings we would have without masks on. I struggled with the variability of the prognosis—I had cared for a 10-year-old with the condition, but the literature reports a median age of death of 2 years. Fiona's parents were devastated with the news—that combination of shock, sadness, and uncertainty laid out on their faces and in their words. Through their tears, they also expressed hope—they told us Fiona would be a fighter.&lt;/p&gt;&lt;p&gt;Fiona did indeed fight and impressed us all with the speed of her recovery. Within a few weeks, she was well enough to go home. Fiona was 5 months old, and it was March 2020.&lt;/p&gt;&lt;p&gt;Fiona's family's life changed right as the world changed amidst the COVID-19 pandemic. Our first follow-up visit was one of my first virtual visits. Instead of that sick, pale baby lying on a bed, I was on screen with a smiling baby at home in a bouncer. We chatted about her health and the unpredictability of the future. There were so many practical matters to consider which changed the way I thought about her care—was it worth risking exposure to COVID to send her to the lab? She would benefit from therapies, but would it be safe to have those providers in the home?&lt;/p&gt;&lt;p&gt;At our visit when Fiona was 6 months of age, some of my own fears about her prognosis were dispelled. She was rolling! She laughed and she babbled. She loved playing with her big siblings. Aside from some mild delays, I would not have had any idea she was affected with a mitochondrial disease. At 15 months she was trying to crawl, and sometimes saying “mama.” At each visit, I shared in Fiona's mother's joy at her progress.&lt;/p&gt;&lt;p&gt;In May 2021 things took a turn for the worse. Fiona was &lt;i&gt;sick&lt;/i&gt;; the sickest she had been since the hospital stay when we met. A choking episode led to aspiration, respir","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 2-3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263665","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":"Parent Narratives Provide Perspectives on the Experience of Care in Trisomy 18","authors":"Ryann Bierer,&nbsp;Janessa Mladucky,&nbsp;Rebecca Anderson,&nbsp;John C. Carey","doi":"10.1002/ajmg.c.32114","DOIUrl":"10.1002/ajmg.c.32114","url":null,"abstract":"<p>Trisomy 18 syndrome, also known as Edwards syndrome, is the second most common autosomal chromosome syndrome after Down syndrome. Trisomy 18 is a serious medical disorder due to the increased occurrence of structural defects, the high neonatal and infant mortality, and the disabilities observed in older children. Interventions, including cardiac surgery, remain controversial, and the traditional approach is to pursue pure comfort care. While the medical challenges have been well-characterized, there are scant data on the parental views and perspective of the lived experience of rearing a child with trisomy 18. Knowledge of the parental viewpoints can help clinicians guide families through decision-making. Our aim was to identify parents' perspectives by analyzing a series of narratives. In this qualitative study, we collected 46 parent narratives at the 2015 and 2016 conferences of the Support Organization for Trisomy 18 &amp; 13 (SOFT). The participants were asked to “Tell us a story about your experience.” Inductive content analysis and close reading were used to identify themes from the stories. Dedoose, a web-based application to analyze qualitative data, was used to code themes more systematically. Of the identified themes, the most common included <i>Impact of trisomy 18 diagnosis</i> and <i>Surpassing expectations</i>. Other themes included <i>Support from professionals</i>, <i>A child, not a diagnosis</i>, and <i>Trust/lack of trust</i>. We examined the voice and the perspectives of the parents in their challenges in caring for their children with this life-limiting condition. The exploration of the themes can ideally guide clinicians in their approach to the counseling and care of the child in a shared decision-making approach.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 2-3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220192","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":"First a Provider, Now a Patient: Receiving a Devastating Diagnosis Through the Patient Portal","authors":"Alexandra C. Keefe","doi":"10.1002/ajmg.c.32113","DOIUrl":"10.1002/ajmg.c.32113","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":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220193","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":"Perspectives and Insights Into Phenylketonuria: Provider Narratives About the Early Years Following Newborn Screening","authors":"Suzanne Hollander,&nbsp;Harvey Levy,&nbsp;Fran Rohr,&nbsp;Susan Waisbren,&nbsp;Priscila Rincon,&nbsp;Ann Wessel,&nbsp;Stephanie Sacharow","doi":"10.1002/ajmg.c.32111","DOIUrl":"10.1002/ajmg.c.32111","url":null,"abstract":"<p>The understanding of phenylketonuria (PKU), guidelines, and treatment landscape have evolved dramatically over the decades since newborn screen implementation. We capture this rich history from the stories and experiences of a multidisciplinary provider team from Boston Children's Hospital's PKU Clinic, who treated PKU from the early years of newborn screening and who worked together for over 40 years.</p>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 2-3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.c.32111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152985","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":"Shattered Dreams: Reflections on Loss and Resilience","authors":"Taylor Kerrins","doi":"10.1002/ajmg.c.32112","DOIUrl":"10.1002/ajmg.c.32112","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":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131599","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":"Significance of Variants of Uncertain Significance: The Human Cost of Genetic Uncertainty","authors":"Damla Gonullu-Rotman","doi":"10.1002/ajmg.c.32109","DOIUrl":"10.1002/ajmg.c.32109","url":null,"abstract":"<div>\u0000 \u0000 <p>This piece narrates the journey of Maria (name of the mother has been altered to protect the family's privacy), a new mother confronting her newborn's unexpected diagnosis of very long chain acyl-CoA dehydrogenase (VLCAD) deficiency, despite undergoing proactive genetic carrier screening within a consanguineous marriage. It highlights the emotional and systemic challenges arising from the lack of diversity in genetic databases, which, in this case, failed to detect pathogenic variants in Maria and her husband. Maria's story sheds light on situations where a masked variant of uncertain significance (VUS) necessitates consultation with a trained genetics specialist and underscores the urgent need for a more equitable healthcare system.</p>\u0000 </div>","PeriodicalId":7445,"journal":{"name":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics","volume":"196 2-3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103417","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}