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. 2024 Sep:158:57-65.
doi: 10.1016/j.pediatrneurol.2024.06.002. Epub 2024 Jun 11.

Congenital Myasthenic Syndromes in Belgium: Genetic and Clinical Characterization of Pediatric and Adult Patients

Nathalie Smeets  1 , Alexander Gheldof  2 , Bart Dequeker  2 , Margaux Poleur  3 , Sofia Maldonado Slootjes  4 , Vinciane Van Parijs  4 , Nicolas Deconinck  5 , Pauline Dontaine  5 , Alicia Alonso-Jimenez  6 , Jan De Bleecker  7 , Willem De Ridder  6 , Sarah Herdewyn  7 , Stéphanie Paquay  8 , Arnaud Vanlander  9 , Liesbeth De Waele  10 , Geertrui Peirens  10 , Diane Beysen  11 , Kristl G Claeys  12 , Nicolas Dubuisson  4 , Isabelle Hansen  13 , Gauthier Remiche  14 , Sara Seneca  2 , Véronique Bissay  15 , Luc Régal  16
Affiliations
Free article

Congenital Myasthenic Syndromes in Belgium: Genetic and Clinical Characterization of Pediatric and Adult Patients

Nathalie Smeets et al. Pediatr Neurol. 2024 Sep.
Free article

Abstract

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.

Keywords: Belgium; CHRNE; Congenital myasthenic syndrome; Electrophysiology; Molecular genetics; Neuromuscular junction; Treatment.

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Conflict of interest statement

Declaration of competing interest There has been no commercial involvement in the study design or manuscript preparation, and none of the authors report any other conflicts of interest.