Congenital myasthenic syndromes in Türkiye: genetic and clinical spectrum revisited in a nationwide pediatric cohort.
TL;DR
The results highlight the major contribution of a limited number of genes and underscore the importance of early molecular diagnosis in a population with high consanguinity and underscore the importance of early molecular diagnosis in a population with high consanguinity.
Abstract
Congenital myasthenic syndromes (CMS) are inherited disorders caused by defects in proteins essential for neuromuscular transmission. In this nationwide, multicenter retrospective study, we analyzed 133 genetically confirmed CMS cases from 118 unrelated families between 2017 and 2024 across 28 centers in Türkiye. Clinical, electrophysiological, and genetic data were collected from medical records. In addition, we performed a PubMed-based review of previously reported genetically confirmed Turkish CMS cases to place our findings in a broader national context. The median age at symptom onset, and the median diagnostic delay were 6 months and 24 months, respectively. Ocular involvement was the most common clinical feature, followed by respiratory and bulbar involvement. High consanguinity (82%) contributed to a predominance of homozygous variants. Variants were identified in 16 CMS-associated genes, with COLQ (34.6%), CHRNE (24.1%), and CHAT (12.8%) being the most frequent. Postsynaptic CMS was the most common anatomical subgroup. Eighteen novel variants across 11 genes expanded the mutational spectrum of CMS. Review of 23 previously published studies from Türkiye identified 139 additional genetically confirmed cases, showing a broadly similar genetic distribution, with CHRNE and COLQ predominating, followed by CHAT, whereas other CMS-associated genes were reported only sporadically. >These findings define the clinical and genetic landscape of CMS in Türkiye and, together with previously published Turkish cases, provide a broad national overview based on 272 genetically confirmed cases. The results highlight the major contribution of a limited number of genes and underscore the importance of early molecular diagnosis in a population with high consanguinity.