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Table of Contents, Volume 196, Number 1, March 2024 Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2024-03-12
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Cover Image, Volume 196, Number 1, March 2024 Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2024-03-12
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An extra X chromosome among adult women in the Million Veteran Program: A more benign perspective of trisomy X Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2024-03-05 Shanlee M. Davis, Craig C. Teerlink, Julie A. Lynch, Natalia Klamut, Bryan R. Gorman, Meghana S. Pagadala, Matthew S. Panizzon, Victoria C. Merritt, Giulio Genovese, Judith L. Ross, Richard L. Hauger
Despite affecting in 1 in every 1000 females, remarkably little is known about trisomy X syndrome (47,XXX), especially among older adults who are undiagnosed. In this study, we aimed to determine the prevalence of 47,XXX among females enrolled in the Million Veterans Program (MVP; mean age 50.2 ± 13.6 years), and compare broad health outcomes between females with 47,XXX and 46,XX matched controls.
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The National Institutes of Health INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project: Accelerating research discoveries for people with Down syndrome across the lifespan Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2024-01-10 Sujata Bardhan, Huiqing Li, Erika Tarver, Charlene Schramm, Marishka Brown, Linda Garcia, Bryanna Schwartz, Anna Mazzucco, Nikila Natarajan, Elizabeth Walsh, Laurie Ryan, Gail Pearson, Melissa A. Parisi
The National Institutes of Health (NIH) has a long-standing history of support for research in Down syndrome (DS). In response to a 2018 congressional directive for a trans-NIH initiative to address medical issues in DS, NIH launched the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Reflecting the three INCLUDE components of basic science
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Cover Image, Volume 193, Number 4, December 2023 Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-12-29
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Retrospective review of the code status of individuals with Down syndrome during the COVID-19 era Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-12-12 Jennifer Jett, Alexander Fossi, Heather Blonsky, Wendy Ross, Sabra Townsend, Mary M. Stephens, Brian Chicoine, Stephanie L. Santoro
Code status is a label in the medical record indicating a patient's wishes for end-of-life (EOL) care in the event of a cardiopulmonary arrest. People with intellectual disabilities had a higher risk of both diagnosis and mortality from coronavirus infections (COVID-19) than the general population. Clinicians and disability advocates raised concerns that bias, diagnostic overshadowing, and ableism
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Listening to patients with suspected genetic diagnoses: A narrative perspective Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-12-04 Robert B. Slocum, Anna C. E. Hurst, Ellis Shelley, Lisa Berry, Robert J. Hopkin, Alyssa L. Rippert, Elizabeth Bhoj, John M. Graham, Katheryn Grand, Aixa Gonzalez, Yuri A. Zarate
CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest.
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Takotsubo cardiomyopathy secondary to electroconvulsive therapy in a young adult with Down syndrome regression disorder Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-12-01 María del Carmen Ortega, José Pablo Bullard, María del Mar Unceta, Felipe Ortuño Sánchez-Pedreño, Patricio Molero, Diego Real de Asúa
We report the case of an 18-year-old woman with Down syndrome (DS) who developed Takotsubo cardiomyopathy (TSC) immediately after the administration of electroconvulsive therapy (ECT), a treatment prescribed for Down syndrome regression disorder resistant to oral psychotropic drugs. TSC is a nonischemic cardiomyopathy related to psychological or physical stress, which has been described as a rare complication
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Children with Down syndrome who experience developmental skill loss, characterization, and phenomenology: A case series Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-11-16 Susana Bernad-Ripoll, Meghan O'Neill, George T. Capone
Loss of previously acquired developmental skills in children with Down syndrome (DS) is not a well characterized phenomenon. We identified 20 confirmed cases of childhood-onset skill loss for descriptive analysis. Eligible participants were recruited from a specialty clinic for persons with DS at a large medical center. Age and gender-matched participants also with DS but without skill loss were used
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Health care satisfaction and medical literacy habits among caregivers of individuals with Down syndrome Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-11-09 Heidi Berger, Jill Wittman, Katelyn Smith, Nora Horick, Kenneth Norris, Allison Young, Javier Magana Gomez, Kenia Kristel Esparza Ocampo, Brian G. Skotko
Patients with Down syndrome have significant specialized health care needs. Our objective was to understand the needs, satisfaction, and online habits of caregivers as they care for persons with Down syndrome. A mixed-method survey was distributed through REDCap from April 2022 to June 2022 in the United States; a Spanish-translated version was distributed through SurveyMonkey from August 2022 to March
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Family adaptation in families of individuals with Down syndrome from 12 countries Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-11-06 Marcia Van Riper, George J. Knafl, Kathleen A. Knafl, Maria do Céu Barbieri-Figueiredo, Sivia Barnoy, Maria Caples, Hyunkyung Choi, Beth Cosgrove, Elysângela Dittz Duarte, Junko Honda, Elena Marta, Supapak Phetrasuwan, Sara Alfieri, Margareth Angelo, Wannee Deoisres, Louise Fleming, Aline Soares dos Santos, Maria João Rocha da Silva
Our current understanding of adaptation in families of individuals with Down syndrome (DS) is based primarily on findings from studies focused on participants from a single country. Guided by the Resiliency Model of Family Stress, Adjustment, and Adaptation, the purpose of this cross-country investigation, which is part of a larger, mixed methods study, was twofold: (1) to compare family adaptation
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Normal joint range of motion in children with Down syndrome Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-11-02 Jordan T. Jones, Nasreen Talib, Emily Cramer, Meg E. Gasparovich, Elizabeth N. Schroeder, Matthew McLaughlin, Jacqueline Kitchen
Down syndrome (DS) is one of the most common chromosomal conditions that results in intellectual disability. Children with DS have many different inflammatory and noninflammatory conditions that can affect joint mobility leading to arthralgia and altered joint range of motion (ROM), and it is important to have normal reference values for comparison to determine the degree of impairment. The objective
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The Pediatric Integrated Care Survey (PICS) in a multidisciplinary clinic for Down syndrome Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-10-31 Shri Karri, Ayesha Harisinghani, Clorinda Cottrell, Stephanie L. Santoro
The Pediatric Integrated Care Survey (PICS) is validated for use to measure the caregiver reported experience of integration and efficiency of all the aspects of their child. We began using the PICS survey to track changes in the patient experience, including throughout changing models of care during the COVID-19 pandemic. From February 2019 to June 2023, 62 responses from caregivers of individuals
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Quality of life measures in children with Down syndrome with disorders of gut–brain interaction Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-10-26 Steven L. Ciciora, Kandamurugu Manickam, Miguel Saps
Down syndrome (DS) is associated with multiple medical comorbidities. Perhaps related to such, caregivers of individuals with DS report lower quality of life (QoL) compared to individuals without DS. It has been shown that disorders of gut-brain interaction (DGBI) such as functional constipation (FC) and irritable bowel syndrome (IBS) are common in individuals with DS. We measured caregiver-reported
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Co-occurring conditions in Down syndrome: Findings from a clinical database Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-10-24 Nicole T. Baumer, Margaret A. Hojlo, Katherine G. Pawlowski, Anna L. Milliken, Angela M. Lombardo, Sabrina Sargado, Cara Soccorso, Emily J. Davidson, William J. Barbaresi
Individuals with Down syndrome (DS) experience a range of medical and neurodevelopmental conditions, necessitating systematic study of their occurrence and impact on neurodevelopmental outcomes. We describe the prevalence and relationships of medical, neurodevelopmental (ND), and mental health (MH) conditions in children with DS. We created a prospective clinical database of individuals with DS, integrated
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Psychopharmacological treatments in Down syndrome and autism spectrum disorder: State of the research and practical considerations Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-10-23 Nicole T. Baumer, George Capone
Individuals with Down syndrome (DS) or Autism Spectrum Disorder (ASD), and especially those with both DS and co-occurring ASD (DS + ASD) commonly display behavioral and psychiatric symptoms that can impact quality of life and places increased burden on caregivers. While the mainstay of treatment in DS and ASD is focused on educational and behavioral therapies, pharmacological treatments can be used
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Altered sleep architecture in children and adolescents with Down syndrome Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-10-23 Kelly J. Gardner, Wei Wang, Elizabeth B. Klerman
Children with Down syndrome (DS) may experience changes in sleep architecture (i.e., different sleep stages) that then affect waketime functioning, including learning, mood, and disruptive behavior. For designing and testing interventions, it is important to document any differences in sleep architecture in children with DS with and without co-occurring diagnoses, including neuropsychiatric diagnoses
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Pneumonia vaccine response in individuals with Down syndrome at three specialty clinics Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-10-20 Stephanie L. Santoro, Carolyn H. Baloh, Sarah J. Hart, Nora Horick, Priya S. Kishnani, Kavita Krell, Nicolas M. Oreskovic, Mikayla Shaffer, Nasreen Talib, Amy Torres, Gail A. Spiridigliozzi, Brian G. Skotko
Individuals with Down syndrome (DS) have been particularly impacted by respiratory conditions, such as pneumonia. However, the description of co-occurring recurrent infections, the response to pneumococcal immunization, and the association of these was previously unknown. We screened individuals with DS using an 11-item screener and prospectively collected pneumococcal titers and laboratory results
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Brief report: Physical activity assessment and counseling in adults with Down syndrome Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-10-05 Ayesha Harisinghani, Amy Torres, Nicolas M. Oreskovic
Adults with Down syndrome are at an increased risk for developing certain medical conditions, which can be further exacerbated by lower levels of physical activity. Physician counseling can provide a supportive environment to encourage modes of physical activity accessible to patients and caregivers. While some adults with Down syndrome have access to a Down syndrome specialty clinic, most are followed
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Ophthalmologic and neuro-ophthalmologic findings in children with Down syndrome Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-10-04 Aarushi Jain, Natalie K. Boyd, Kelli C. Paulsen, Benjamin N. Vogel, Lina Nguyen, Jonathan D. Santoro
Down syndrome, also known as Trisomy 21, is a genetic disorder associated with mild-to-moderate intellectual disability, delays in growth, and characteristic facial features. A wide range of ocular complications are seen in children with Down syndrome, including strabismus, nystagmus, refractive errors, congenital cataracts, the presence of keratoconus, and decreased visual acuity. Early ophthalmic
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Cover Image, Volume 193, Number 3, September 2023 Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-09-30 Swaroop Aradhya, Flavia M. Facio, Hillery Metz, Toby Manders, Alexandre Colavin, Yuya Kobayashi, Keith Nykamp, Britt Johnson, Robert L. Nussbaum
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Beyond chromosome analysis: Additional genetic testing practice in a Down syndrome clinic Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-09-29 Ayesha Harisinghani, Gabriella Raffaele, Carrie Blout Zawatsky, Stephanie L. Santoro
Down syndrome (DS) and other genetic conditions have been reported to co-occur in the same person. This study sought to examine the genetic evaluation beyond chromosome analysis of individuals with DS at one DS specialty clinic. Retrospective chart review of genetic testing performed beyond chromosome analysis, the indication for the genetic testing, and the result of the genetic testing from the electronic
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Healthy transition: Roadmap for young adults with Down syndrome to adulthood Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-09-25 Maya Weaver, Andrew McCormick
Healthcare transition is the purposeful and planned process for preparing young adults with Down syndrome for an adult oriented healthcare system. Significant gaps of a delayed, incomplete, siloed and decentered transition can be avoided when transition is approached in a longitudinal and holistic manner. Young adults with Down syndrome are specifically vulnerable to these gaps as the combination of
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Sustainability of personal social networks of people with Down syndrome Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-09-22 Ayesha Harisinghani, Amar Dhand, Ellen Hollands Steffensen, Brian G. Skotko
Research continues to demonstrate that the characteristics of one's social network could have an impact on the development of Alzheimer's disease. Given the predisposition of people with Down syndrome to develop Alzheimer's disease, analysis of their social networks has become an emerging focus. Previous pilot research demonstrated that the personal networks of people with DS could be quantitatively
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Integration of EpiSign, facial phenotyping, and likelihood ratio interpretation of clinical abnormalities in the re-classification of an ARID1B missense variant Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-08-31 Caitlin Forwood, Katie Ashton, Ying Zhu, Futao Zhang, Kerith-Rae Dias, Krystle Standen, Carey-Anne Evans, Louise Carey, Michael Cardamone, Carolyn Shalhoub, Hala Katf, Carlos Riveros, Tzung-Chien Hsieh, Peter Krawitz, Peter N Robinson, Tracy Dudding-Byth, Bekim Sadikovic, Jason Pinner, Michael F. Buckley, Tony Roscioli
Heterozygous ARID1B variants result in Coffin–Siris syndrome. Features may include hypoplastic nails, slow growth, characteristic facial features, hypotonia, hypertrichosis, and sparse scalp hair. Most reported cases are due to ARID1B loss of function variants. We report a boy with developmental delay, feeding difficulties, aspiration, recurrent respiratory infections, slow growth, and hypotonia without
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Is artificial intelligence getting too much credit in medical genetics? Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-08-22 Imen F. Alkuraya
Artificial intelligence has lately proven useful in the field of medical genetics. It is already being used to interpret genome sequences and diagnose patients based on facial recognition. More recently, large-language models (LLMs) such as ChatGPT have been tested for their capacity to provide medical genetics information. It was found that ChatGPT performed similarly to human respondents in factual
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Computational facial analysis for rare Mendelian disorders Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-08-16 Tzung-Chien Hsieh, Peter M. Krawitz
With the advances in computer vision, computational facial analysis has become a powerful and effective tool for diagnosing rare disorders. This technology, also called next-generation phenotyping (NGP), has progressed significantly over the last decade. This review paper will introduce three key NGP approaches. In 2014, Ferry et al. first presented Clinical Face Phenotype Space (CFPS) trained on eight
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Artificial intelligence and the impact on medical genetics Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-08-10 Benjamin D. Solomon, Wendy K. Chung
Virtually all areas of biomedicine will be increasingly affected by applications of artificial intelligence (AI). We discuss how AI may affect fields of medical genetics, including both clinicians and laboratorians. In addition to reviewing the anticipated impact, we provide recommendations for ways in which these groups may want to evolve in light of the influence of AI. We also briefly discuss how
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Development of webcam-collected and artificial-intelligence-derived social and cognitive performance measures for neurodevelopmental genetic syndromes Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-08-03 Thomas W. Frazier, Robyn M. Busch, Patricia Klaas, Katherine Lachlan, Shafali Jeste, Alexander Kolevzon, Eva Loth, Jacqueline Harris, Leslie Speer, Tom Pepper, Kristin Anthony, J. Michael Graglia, Christal G. Delagrammatikas, Sandra Bedrosian-Sermone, Constance Smith-Hicks, Katie Huba, Robert Longyear, LeeAnne Green-Snyder, Frederick Shic, Mustafa Sahin, Charis Eng, Antonio Y. Hardan, Mirko Uljarević
This study focused on the development and initial psychometric evaluation of a set of online, webcam-collected, and artificial intelligence-derived patient performance measures for neurodevelopmental genetic syndromes (NDGS). Initial testing and qualitative input was used to develop four stimulus paradigms capturing social and cognitive processes, including social attention, receptive vocabulary, processing
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Application of facial analysis Technology in Clinical Genetics: Considerations for diverse populations Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-08-03 Paul Kruszka, Cedrik Tekendo-Ngongang
Facial analysis technology in rare diseases has the potential to shorten the diagnostic odyssey by providing physicians with a valuable diagnostic tool. Given that most clinical genetic resources focus on populations of European descent, we compare craniofacial features in genetic syndromes across different populations and review how machine learning algorithms perform on diagnosing genetic syndromes
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Applications of artificial intelligence in clinical laboratory genomics Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-07-28 Swaroop Aradhya, Flavia M. Facio, Hillery Metz, Toby Manders, Alexandre Colavin, Yuya Kobayashi, Keith Nykamp, Britt Johnson, Robert L. Nussbaum
The transition from analog to digital technologies in clinical laboratory genomics is ushering in an era of “big data” in ways that will exceed human capacity to rapidly and reproducibly analyze those data using conventional approaches. Accurately evaluating complex molecular data to facilitate timely diagnosis and management of genomic disorders will require supportive artificial intelligence methods
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Cover Image, Volume 193, Number 2, June 2023 Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-06-21
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Unmasking the challenges of Kabuki syndrome in adulthood: A case series Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-06-09 Jessica R. C. Priestley, Alyssa L. Rippert, Courtney Condit, Kosuke Izumi, Staci Kallish, Theodore G. Drivas
Kabuki syndrome is a recognizable Mendelian disorder characterized by the clinical constellation of childhood hypotonia, developmental delay or intellectual impairment, and characteristic dysmorphism resulting from monoallelic pathogenic variants in KMT2D or KDM6A. In the medical literature, most reported patients are children, and data is lacking on the natural history of the condition across the
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Autosomal dominant genodermatoses in adults being heralded by superimposed skin lesions in children Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-06-08 Rudolf Happle
In autosomal dominant skin disorders, pronounced mosaic involvement may sometimes occur in the neonate, originating in a heterozygous embryo from early loss of heterozygosity, probably during the first week after fertilization. In biallelic phenotypes, such overlaying mosaic involvement may coexist with disseminated mosaicism, for example, in neurofibromatosis or tuberous sclerosis. In other phenotypes
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Spectrum of white matter abnormalities associated with FOXC1-related disorders in two unrelated cases Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-05-31 Tasnim Tabassum, D'Agostino Maria Daniela, Roberta La Piana
The purpose of this study is to document the wide spectrum of white matter abnormalities associated with FOXC1 pathogenic variants. We report two adult individuals—a 60-year-old individual and a 24-year-old one, presenting with hearing loss, anterior eye segment dysgenesis, and very different severity of cerebral small vessel disease. Molecular testing documented the presence of FOXC1 pathogenic variants
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Neurodevelopmental and other psychiatric disorders in 22q11.2 deletion syndrome from childhood to adult age: Prospective longitudinal study of 100 individuals Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-05-29 Lena Wallin, Christopher Gillberg, Elisabeth Fernell, Carina Gillberg, Eva Billstedt
The 22q11.2 deletion syndrome (22q11.2DS), affects physical as well as cognitive and emotional functioning with increased risk for psychiatric and behavioral problems. This longitudinal study of 79 individuals (18–50 years) with 22q11.2DS investigated neurodevelopmental (NDD) and psychiatric disorders in adulthood, evaluated the stability of childhood diagnoses over time, and examined associations
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Spondyloepimetaphyseal dysplasia with joint laxity type 2: Aggregating the literature and reporting on the life of a 66-year-old man Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-05-24 Alexander Beke, Karina da Costa Silveira, Taryn Athey, Peter Kannu
Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (SEMDJL2), is a rare bone dysplasia that results from hotspot (amino acids148/149) mutations in KIF22. Clinically, affected individuals present with generalized joint laxity, limb malalignment, midface hypoplasia, gracile digits, postnatal short stature, and occasionally, tracheolaryngomalacia; additionally, radiological features
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Rod-cone dystrophy in an adult with GNB1-related disorder: An expansion of the phenotype and natural history Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-05-22 Xiao-Ru Yang, Faazil Kassam, A. Micheil Innes
GNB1-related disorder is characterized by intellectual disability, abnormal tone, and other variable neurologic and systemic features. GNB1 encodes the β1 subunit of the heterotrimeric G-protein, a complex with a key role in signal transduction. Consistent with its particularly high expression in rod photoreceptors, Gβ1 forms a subunit of retinal transducin (Gαtβ1γ1), which mediates phototransduction
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Adult experiences in Beckwith–Wiedemann syndrome Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-05-10 William A. Drust, Alessandro Mussa, Andrea Gazzin, Pablo Lapunzina, Jair Tenorio-Castaño, Julian Nevado, Patricia Pascual, Pedro Arias, Alejandro Parra, Kelly D. Getz, Jennifer M. Kalish
Beckwith–Wiedemann syndrome (BWS) is an overgrowth and epigenetic disorder caused by changes on chromosome 11p15. The primary features requiring management in childhood include macroglossia, omphalocele, lateralized overgrowth, hyperinsulinism, and embryonal tumors. Management guidelines have not been developed for adults with BWS and there have been few studies to assess the clinical needs of these
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Autism and mild epilepsy associated with a de novo missense pathogenic variant in the GTPase effector domain of DNM1 Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-05-03 Davide Mei, Elena Parrini, Claudia Bianchini, Maria Luisa Ricci, Renzo Guerrini
Dynamin 1 is a GTPase protein involved in synaptic vesicle fission, which facilitates the exocytosis of neurotransmitters necessary for normal signaling. Pathogenic variants in the DNM1 gene are associated with intractable epilepsy, often manifested as infantile spasms at onset, developmental delay, and a movement disorder, and are located in the GTPase and middle domains of the protein. We describe
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Mental health in adults living with arthrogryposis multiplex congenita Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-04-27 Shirromi Sarveswaran, William Ben Mortenson, Bonita Sawatzky
Little is known about the mental well-being of adults living with arthrogryposis multiplex congenita (AMC). The objectives of this study were to determine the incidence of depression in an international population of adults with AMC and to identify variables independently associated with depression. This cross-sectional study used independent samples t-test and hierarchical multiple regression. The
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DNAJC21-related thrombocytopenia in a young adult female Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-04-26 Deniz Aslan, Ozlem Akgun-Dogan, Beril Ay, Mahmut Orhun Çamurdan, Hanifenur Mancılar, Yasemin Alanay
Bone marrow failure type 3 (BMFS3) (MIM:617052) is a subtype of inherited bone marrow failure syndromes (IBMFS) caused by homozygous pathogenic variants in DNAJC21. It was first defined in 2016, and to date, 19 patients have been reported. Here we report the first adult patient; a 20-year-old female with a novel frameshift variant in DNAJC21 presents with thrombocytopenia, dysmorphic findings, and
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Caregivers' concerns and supports needed to care for adults with Down syndrome Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-04-18 Erica De La Garza, Ashley Scott, Hampus Hillerstrom, James Hendrix, Eric Rubenstein
Research regarding caregivers for individuals with Down syndrome mainly focuses on outcomes for the pediatric population and not on the experience of caregivers themselves. Our objective was to understand caregiver-reported experiences and concerns for themselves and the individual they care for through a survey of caregivers of adults with Down syndrome. We conducted a survey of N = 438 caregivers
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Age-related survey of clinical genetics literature and related resources Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-04-12 Amelia M. Solomon, Benjamin D. Solomon
Genetic conditions affect people throughout their entire lifespan; however, many clinical geneticists focus on the care of pediatric individuals. We analyzed the medical literature and related resources to help assess to what extent adults with genetic diseases were represented. This included general literature searches of PubMed (from 2001 through 2022), specific databases (the FDA orphan drug list
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Cover Image, Volume 193, Number 1, March 2023 Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-03-23
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COL1A1 and COL1A2 variants in Ehlers-Danlos syndrome phenotypes and COL1-related overlap disorder Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-03-09 Elise Venable, Dacre R. T. Knight, Emily K. Thoreson, Linnea M. Baudhuin
Pathogenic variants in COL1A1 and COL1A2 are involved in osteogenesis imperfecta (OI) and, rarely, Ehlers-Danlos syndrome (EDS) subtypes and OI-EDS overlap syndromes (OIEDS1 and OIEDS2, respectively). Here we describe a cohort of 34 individuals with likely pathogenic and pathogenic variants in COL1A1 and COL1A2, 15 of whom have potential OIEDS1 (n = 5) or OIEDS2 (n = 10). A predominant OI phenotype
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When is the best time to screen and evaluate for treatable genetic disorders?: A lifespan perspective Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-03-06 Melissa A. Parisi, Michele Caggana, Jennifer L. Cohen, Nina B. Gold, Jill A. Morris, Joseph J. Orsini, Tiina K. Urv, Melissa P. Wasserstein
This paper focuses on the question of, “When is the best time to identify an individual at risk for a treatable genetic condition?” In this review, we describe a framework for considering the optimal timing for pursuing genetic and genomic screening for treatable genetic conditions incorporating a lifespan approach. Utilizing the concept of a carousel that represents the four broad time periods when
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Gene-targeted therapies: Overview and implications Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-03-02 P J Brooks, Tiina K. Urv, Melissa A. Parisi
Gene-targeted therapies (GTTs) are therapeutic platforms that are in principle applicable to large numbers of monogenic diseases. The rapid development and implementation of GTTs have profound implications for rare monogenic disease therapy development. This article provides a brief summary of the primary types of GTTs and a brief overview of the current state of the science. It also serves as a primer
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A review of economic issues for gene-targeted therapies: Value, affordability, and access Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-02-28 Louis P. Garrison, Andrew W. Lo, Richard S. Finkel, Patricia A. Deverka
The National Center for Advancing Translational Sciences' virtual 2021 conference on gene-targeted therapies (GTTs) encouraged multidisciplinary dialogue on a wide range of GTT topic areas. Each of three parallel working groups included social scientists and clinical scientists, and the three major sessions included a presentation on economic issues related to their focus area. These experts also coordinated
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Privacy, bias and the clinical use of facial recognition technology: A survey of genetics professionals Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-02-07 Elias Aboujaoude, Janice Light, Julia E. H. Brown, W. John Boscardin, Benedikt Hallgrímsson, Ophir D. Klein
Facial recognition technology (FRT) has been adopted as a precision medicine tool. The medical genetics field highlights both the clinical potential and privacy risks of this technology, putting the discipline at the forefront of a new digital privacy debate. Investigating how geneticists perceive the privacy concerns surrounding FRT can help shape the evolution and regulation of the field, and provide
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Moving away from one disease at a time: Screening, trial design, and regulatory implications of novel platform technologies Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-02-04 Julie Lekstrom-Himes, P J Brooks, Dwight D. Koeberl, Amy Brower, Aaron Goldenberg, Robert C. Green, Jill A. Morris, Joseph J. Orsini, Timothy W. Yu, Erika F. Augustine
Most rare diseases are caused by single-gene mutations, and as such, lend themselves to a host of new gene-targeted therapies and technologies including antisense oligonucleotides, phosphomorpholinos, small interfering RNAs, and a variety of gene delivery and gene editing systems. Early successes are encouraging, however, given the substantial number of distinct rare diseases, the ability to scale
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Natural history of MRAS-related Noonan syndrome: Evidence of mild adult-onset left ventricular hypertrophy and neuropsychiatric features Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-02-03 Manuela Priolo, Cecilia Mancini, Francesca Clementina Radio, Luigi Chiriatti, Andrea Ciolfi, Camilla Cappelletti, Viviana Cordeddu, Letizia Pintomalli, Alfredo Brusco, Corrado Mammi, Marco Tartaglia
Gain of function pathogenic variants in MRAS have been found in a small subset of pediatric subjects presenting with Noonan syndrome (NS) associated with hypertrophic cardiomyopathy (HCM) and moderate to severe intellectual disability. These variants are considered to confer a high-risk for the development of severe HCM with poor prognosis and fatal outcome. We report on the natural history of the
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Are we prepared to deliver gene-targeted therapies for rare diseases? Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-01-24 Timothy W. Yu, Stephen F. Kingsmore, Robert C. Green, Tippi MacKenzie, Melissa Wasserstein, Michele Caggana, Nina B. Gold, Annie Kennedy, Priya S. Kishnani, Matthew Might, Phillip J. Brooks, Jill A. Morris, Melissa A. Parisi, Tiina K. Urv
The cost and time needed to conduct whole-genome sequencing (WGS) have decreased significantly in the last 20 years. At the same time, the number of conditions with a known molecular basis has steadily increased, as has the number of investigational new drug applications for novel gene-based therapeutics. The prospect of precision gene-targeted therapy for all seems in reach… or is it? Here we consider
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Gene-targeted therapies: Towards equitable development, diagnosis, and access Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-01-23 Amy M. Gaviglio, Mark W. Skinner, Lily J. Lou, Richard S. Finkel, Erika F. Augustine, Aaron J. Goldenberg
Genomic and gene-targeted therapies hold great promise in addressing the global issue of rare diseases. To achieve this promise, however, it is critical the twin goals of equity in access to testing and diagnosis, and equity in access to therapy be considered early in the life cycle of development and implementation. Rare disease researchers and clinicians must simultaneously recognize the life-altering
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Cover Image, Volume 190, Number 1, March 2022 Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-01-06
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Data sharing to advance gene-targeted therapies in rare diseases Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2023-01-03 Julie Lekstrom-Himes, Erika F. Augustine, Amy Brower, Thomas Defay, Richard S. Finkel, Amy L. McGuire, Mark W. Skinner, Timothy W. Yu
Recent advancements in gene-targeted therapies have highlighted the critical role data sharing plays in successful translational drug development for people with rare diseases. To scale these efforts, we need to systematize these sharing principles, creating opportunities for more rapid, efficient, and scalable drug discovery/testing including long-term and transparent assessment of clinical safety
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Molecular advances, clinical management, and treatment opportunities in RASopathies. Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2022-12-21 Chiara Leoni,Giovanni Neri
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Dermatological manifestations, management, and care in RASopathies Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2022-12-21 Maria Ines Kavamura, Chiara Leoni, Giovanni Neri
RASopathies are rare genetic disorders caused by germline pathogenic variants in genes belonging to the RAS/MAPK pathway, which signals cell proliferation, differentiation, survival and death. The dysfunction of such signaling pathway causes syndromes with overlapping clinical manifestations. Skin and adnexal lesions are the cardinal clinical signs of RASopathies, such as cardiofaciocutaneous syndrome
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Cancer incidence and surveillance strategies in individuals with RASopathies Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2022-12-19 Gina Ney, Andrea Gross, Alicia Livinski, Christian P. Kratz, Douglas R. Stewart
RASopathies are a set of clinical syndromes that have molecular and clinical overlap. Genetically, these syndromes are defined by germline pathogenic variants in RAS/MAPK pathway genes resulting in activation of this pathway. Clinically, their common molecular signature leads to comparable phenotypes, including cardiac anomalies, neurologic disorders and notably, elevated cancer risk. Cancer risk in
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New prospectives on treatment opportunities in RASopathies Am. J. Med. Genet. Semin. Med. Genet. Part C (IF 3.1) Pub Date : 2022-12-19 Bruce D. Gelb, Marielle E. Yohe, Cordula Wolf, Gregor Andelfinger
The RASopathies are a group of clinically defined developmental syndromes caused by germline variants of the RAS/mitogen-activated protein (MAPK) cascade. The prototypic RASopathy is Noonan syndrome, which has phenotypic overlap with related disorders such as cardiofaciocutaneous syndrome, Costello syndrome, Noonan syndrome with multiple lentigines, and others. In this state-of-the-art review, we summarize