Cardiovascular abnormalities in patients with SHANK3 pathogenic variants: Beyond neurodevelopmental disorders and epilepsy.

Autor: Esmel-Vilomara R; Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Pediatric Cardiology Unit, Department of Pediatrics. Hospital de la Santa Creu i Sant Pau, Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain. Electronic address: roger.esmel@autonoma.cat., Dougherty-De Miguel L; Pediatric Neurology Unit, Department of Pediatrics. Hospital de la Santa Creu i Sant Pau, Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain. Electronic address: lucydoughertydm@gmail.com., Artigas-Baleri A; Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Genetics. Hospital de la Santa Creu i Sant Pau, Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain. Electronic address: aartigas@santpau.cat., Turón-Viñas E; Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Pediatric Neurology Unit, Department of Pediatrics. Hospital de la Santa Creu i Sant Pau, Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain. Electronic address: eturon@santpau.cat., Cuscó I; Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Genetics. Hospital de la Santa Creu i Sant Pau, Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (Spain), Spain. Electronic address: icusco@santpau.cat., Díaz-Gómez A; Pediatric Neurology Unit, Department of Pediatrics. Hospital de la Santa Creu i Sant Pau, Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain. Electronic address: adiazgo@santpau.cat., Panadés-De Oliveira L; Epilepsy Monitoring Unit, Department of Neurology. Hospital del Mar, Barcelona, Spain. Electronic address: lpanadesdeoliveira@psmar.cat., Rocamora R; Epilepsy Monitoring Unit, Department of Neurology. Hospital del Mar, Barcelona, Spain. Electronic address: rrocamora@psmar.cat., Boronat S; Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Pediatric Neurology Unit, Department of Pediatrics. Hospital de la Santa Creu i Sant Pau, Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain. Electronic address: sboronat@santpau.cat.
Jazyk: angličtina
Zdroj: European journal of medical genetics [Eur J Med Genet] 2024 Oct; Vol. 71, pp. 104965. Date of Electronic Publication: 2024 Jul 31.
DOI: 10.1016/j.ejmg.2024.104965
Abstrakt: Neurodevelopmental disorders have been linked to numerous genes, particularly pathogenic variants in genes encoding postsynaptic scaffolding proteins, like SHANK3. This study aims to provide insights into the cardiovascular profile of patients with pathogenic SHANK3 variants, expanding beyond the well-established associations with neurodevelopmental disorders and epilepsy. We conducted a prospective study involving patients affected by neurodevelopmental disorders with pathogenic SHANK3 variants. Comprehensive cardiovascular assessments were performed and molecular genetic testing included chromosomal microarray followed by clinical exome sequencing. We identified five patients with de novo SHANK3 variants, all of whom exhibited cardiac involvement, including myocardial dysfunction, congenital heart disease (patent ductus arteriosus), and a case of postictal atrial fibrillation. Our findings emphasize an elevated risk of cardiovascular abnormalities in patients with SHANK3 pathogenic variants compared to prior reports. Despite their young age, these patients displayed significant cardiac abnormalities. The study highlights the necessity of integrating cardiac evaluation and ongoing cardiovascular monitoring into multidisciplinary care, facilitating early detection of heart failure and assessment of the risk of sudden unexpected death in epilepsy (SUDEP). Further research is needed to elucidate the underlying mechanisms of cardiac manifestations in SHANK3 mutation carriers.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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