Aim:

To describe phenotype-genotype correlation in a cohort of children with genetically conformed congenital myasthenic syndrome (CMS)

Methods:

Retrospective chart review of children with genetically proven CMS from January 2015 to April 2018 was analysed for clinical profile, electrophysiology and response to treatment

Results:

Twenty three children were included. Genetic panel (NGS) included CHRNE, RAPSYN, COLQ, DOK7 and GFPT1.  12(54%) had mutations in CHRNE gene, 6 (27%) in COLQ, 3 (14%) in GFPT1 and one each with RAPSYN and DOK7 gene. The mean age at presentation was 4.9 years (range of 1 to 14 years) in CHRNE cohort, 5.25 years (0.5 to 10 years) in COLQ, 7.3 years (2 to 11 years) in GFPT1 and 5 years and 16 years in RSPSYN and DOK7 respectively. All patients in CHRNE group had limb involvement with 7(60%) having ocular involvement and 2(16%) with pharyngeal weakness in addition. Children with GFPT1 and RAPSYN mutation had limb girdle phenotype and children with COLQ mutation had generalised involvement.Nerve conduction study was normal in all, except 4 children(2 each in Col Q and CHRNE group) who had motor axonopathy. RNS at 3 Hz revealed significant decrement in all cases. One child in CHRNE group and one child in COLQ group had repetitive CMAPs. Response to treatment with pyridostigmine was good in patients with CHRNE, GFPT1 and RAPSYN, whereas COLQ group has partial response to salbutamol.

Conclusion:

Genotype in CMS plays an integral part in diagnosis, selection of appropriate medications and follow-up.