Congenital Myasthenia

Gene: SYT2

Green List (high evidence)

Mono-allelic disease, PMID 25192047 and 30533528: dominant missense variants in SYT2 reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment in two families. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated.

Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function.

Created: 23 Oct 2020, 7:22 a.m. | Last Modified: 23 Oct 2020, 7:30 a.m.

Panel Version: 0.31

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040; Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive OMIM#619461

Publications

• 25192047
• 32776697
• 32250532
• 30533528