Myhre syndrome in adulthood: clinical variability and emerging genotype-phenotype correlations.

Autor: Vanbelleghem E; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium., Van Damme T; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium., Beyens A; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium., Symoens S; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium., Claes K; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium., De Backer J; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.; Department of Cardiology, Ghent University Hospital, Ghent, Belgium., Meerschaut I; Department of Pediatric Cardiology, University Hospital Brussels, Brussels, Belgium., Vanommeslaeghe F; Department of Nephrology, Ghent University Hospital, Ghent, Belgium., Delanghe SE; Department of Nephrology, Ghent University Hospital, Ghent, Belgium., van den Ende J; Department of Medical Genetics, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium., Beyltjens T; Department of Medical Genetics, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium., Scimone ER; Department of Pediatrics, Genetics Unit, MassGeneral for Children, Boston, MA, USA., Lindsay ME; Cardiovascular Genetics Program, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Pediatric Cardiology Division, Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA., Schimmenti LA; Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA., Hinze AM; Division of Rheumatology, Mayo Clinic, Rochester, MN, USA., Dunn E; Department of Pediatrics, Division of Medical Genetic, Stanford University, Stanford, CA, USA., Gomez-Ospina N; Department of Pediatrics, Division of Medical Genetic, Stanford University, Stanford, CA, USA., Vandernoot I; ULB Center of Human Genetics, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium., Delguste T; ULB Center of Human Genetics, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium., Coppens S; ULB Center of Human Genetics, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium., Cormier-Daire V; Paris Cité University, Centre of Reference for Constitutional Bone Diseases (MOC), Department of Genetics, INSERM UMR 1163, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France., Tartaglia M; Molecular Genetics and Functional Genomics, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Garavelli L; Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy., Shieh J; Institute for Human Genetics and Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA., Demir Ş; Department of Medical Genetics, School of Medicine, Marmara University, Istanbul, Turkey., Arslan Ateş E; Department of Medical Genetics, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey., Zenker M; Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany., Rohanizadegan M; Department of Medicine, Division of Translational Medicine & Human Genetics, University of Pennsylvania, Philadelphia, PA, USA., Rivera-Cruz G; Division of Reproductive Endocrinology and Infertility, Stanford University School of Medicine, Stanford, CA, USA., Douzgou S; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway., Lin AE; Department of Pediatrics, Genetics Unit, MassGeneral for Children, Boston, MA, USA., Callewaert B; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium. bert.callewaert@ugent.be.; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium. bert.callewaert@ugent.be.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2024 Sep; Vol. 32 (9), pp. 1086-1094. Date of Electronic Publication: 2024 Jul 12.
DOI: 10.1038/s41431-024-01664-1
Abstrakt: Myhre syndrome (MS, MIM 139210) is a rare multisystemic disorder caused by recurrent pathogenic missense variants in SMAD4. The clinical features have been mainly documented in childhood and comprise variable neurocognitive development, recognizable craniofacial features, a short stature with a pseudo-muscular build, hearing loss, thickened skin, joint limitations, diverse cardiovascular and airway manifestations, and increased fibrosis often following trauma or surgery. In contrast, adults with MS are underreported obscuring potential clinical variability. Here, we describe 24 adults with MS, including 17 diagnosed after the age of 18 years old, and we review the literature on adults with MS. Overall, our cohort shows a milder phenotype as well as lower mortality rates compared to what has been published in literature. Individuals with a codon 500 variant in SMAD4 present with a more pronounced neurodevelopmental and systemic phenotype. However, in contrast to the literature, we observe cardiovascular abnormalities in individuals with the p.(Arg496Cys) variant. In addition, we describe scoliosis as a new manifestation and we report fertility in two additional males with the p.(Arg496Cys). In conclusion, our study contributes novel insights into the clinical variability of MS and underscores the importance of variant-specific considerations, and we provide recommendations for the management of MS in adulthood.
(© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.)
Databáze: MEDLINE
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