[en] [en] BACKGROUND: Congenital myasthenic syndromes (CMS) are a group of genetic disorders characterized by impaired neuromuscular transmission. CMS typically present at a young age with fatigable muscle weakness, often with an abnormal response after repetitive nerve stimulation (RNS). Pharmacologic treatment can improve symptoms, depending on the underlying defect. Prevalence is likely underestimated. This study reports on patients with CMS followed in Belgium in 2022.
METHODS: Data were gathered retrospectively from the medical charts. Only likely pathogenic and pathogenic variants were included in the analysis.
RESULTS: We identified 37 patients, resulting in an estimated prevalence of 3.19 per 1,000,000. The patients harbored pathogenic variants in CHRNE, RAPSN, DOK7, PREPL, CHRNB1, CHRNG, COLQ, MUSK, CHRND, GFPT1, and GMPPB. CHRNE was the most commonly affected gene. Most patients showed disease onset at birth, during infancy, or during childhood. Symptom onset was at adult age in seven patients, caused by variants in CHRNE, DOK7, MUSK, CHRND, and GMPPB. Severity and distribution of weakness varied, as did the presence of respiratory involvement, feeding problems, and extraneuromuscular manifestations. RNS was performed in 23 patients of whom 18 demonstrated a pathologic decrement. Most treatment responses were predictable based on the genotype.
CONCLUSIONS: This is the first pooled characterization of patients with CMS in Belgium. We broaden the phenotypical spectrum of pathogenic variants in CHRNE with adult-onset CMS. Systematically documenting larger cohorts of patients with CMS can aid in better clinical characterization and earlier recognition of this rare disease. We emphasize the importance of establishing a molecular genetic diagnosis to tailor treatment choices.
Disciplines :
Pediatrics
Author, co-author :
Smeets, Nathalie ; Child Neurology Unit, Department of Pediatrics, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel, Brussels, Belgium. Electronic address: Nathalie.smeets@uzbrussel.be
Gheldof, Alexander; Center of Medical Genetics, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel, Brussels, Belgium
Dequeker, Bart; Center of Medical Genetics, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel, Brussels, Belgium
Poleur, Margaux ; Université de Liège - ULiège > Département des sciences cliniques
Maldonado Slootjes, Sofia ; Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Van Parijs, Vinciane; Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Deconinck, Nicolas; Department of Pediatric Neurology, Queen Fabiola Children's University Hospital, Université Libre De Bruxelles, Brussels, Belgium
Dontaine, Pauline; Department of Pediatric Neurology, Queen Fabiola Children's University Hospital, Université Libre De Bruxelles, Brussels, Belgium
Alonso-Jimenez, Alicia; Department of Neurology, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium
De Bleecker, Jan ; Department of Neurology, Ghent University Hospital, Ghent, Belgium
De Ridder, Willem; Department of Neurology, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium
Herdewyn, Sarah ; Department of Neurology, Ghent University Hospital, Ghent, Belgium
Paquay, Stéphanie; Department of Neuropediatrics, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Vanlander, Arnaud ; Department of Pediatric Neurology and Metabolic Diseases, Ghent University Hospital, Ghent, Belgium
De Waele, Liesbeth ; Department of Development and Regeneration, KU Leuven, Leuven, Belgium, Department of Pediatric Neurology, University Hospitals Leuven, Leuven, Belgium
Peirens, Geertrui; Department of Development and Regeneration, KU Leuven, Leuven, Belgium, Department of Pediatric Neurology, University Hospitals Leuven, Leuven, Belgium
Beysen, Diane; Department of Pediatric Neurology, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium
Claeys, Kristl G; Department of Neurology, University Hospitals Leuven, Leuven, Belgium, Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, Leuven Brain Institute (LBI), Leuven, Belgium
Dubuisson, Nicolas ; Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Hansen, Isabelle; Department of Neurology, University of Liège, Centre Hospitalier Universitaire de Liège, Liège, Belgium
Remiche, Gauthier ; Department of Neurology, Hôpital Universitaire de Bruxelles - Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
Seneca, Sara ; Center of Medical Genetics, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel, Brussels, Belgium
Bissay, Véronique; NEUR Research Group and Department of Neurology, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel, Brussels, Belgium
Régal, Luc; Child Neurology Unit, Department of Pediatrics, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel, Brussels, Belgium
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