Genotypic and phenotypic spectrum of congenital myasthenic syndrome: Insights from Southeastern Türkiye.

Congenital myasthenic syndromes (CMS) are inherited disorders caused by defects of the neuromuscular junction. Both the definitive diagnosis and the treatment are structured in accordance with genetic analysis. We aimed to investigate the clinical and genetic characteristics of CMS in a pediatric cohort from Southeastern Türkiye, a region with high rates of consanguineous marriage. The clinical features and demographic data of fifteen patients (9 girls, 6 boys) with CMS were evaluated. Genetic analysis was performed using clinical exome sequencing. The mean age of patients was 7.4 ± 4.1 years, and the mean age at diagnosis was 5.8 ± 4 years. Symptoms were present from birth in most patients. The latest age at symptom onset was 11 years. The patients presented with ptosis, ophthalmoplegia, muscle weakness, frequent falls, collapse, respiratory distress, dysphagia, and laryngomalacia. Homozygous variants in COLQ (11/15, 73%), CHAT (1), DOK7 (1), RAPSN (1), and a compound heterozygous variant in MYO9A (1) were identified. The same variant, c.444G > A, was detected in all patients with COLQ variants except one, in whom the c.706C > T variant was identified. Epilepsy was observed in three patients (two with COLQ and one with CHAT variants). CMS in Southeastern Türkiye is predominantly caused by COLQ variants, particularly the recurrent c.444G > A nonsense variant, likely reflecting a founder effect in this region with a consanguineous marriage rate of 43%.