Abstract
•Key features of CMS are hypotonia with fatigable muscle weakness.•Pyridostigmine therapy gradually improved our patient's motor milestones.•We found a splicing mutation in VAMP1 by WES, autozygosity mapping and filtering.•RT-PCR unequivocally demonstrated skipping of exon 2.
Congenital myasthenic syndrome comprises several genetic disorders that impair neuromuscular junction transmission. Causative mutations occur in at least 30 genes, approximately 6–8% of which are presynaptic. One such gene, VAMP1, encodes vesicle-associated membrane protein-1, which is crucial in the formation and fusion of synaptic vesicles with the presynaptic membrane at the neuromuscular junction. VAMP1 mutations are associated with two main phenotypes: a) autosomal recessive congenital myasthenic syndrome and b) autosomal dominant spastic ataxia 1. We report a girl from a consanguineous Saudi family presenting with hypotonia, developmental delay, feeding difficulties and floppiness since birth. Comprehensive genetic testing revealed a homozygous splicing mutation in VAMP1. RT-PCR confirmed the presence of an aberrant transcript causing skipping of exon 2 in the gene.