[PS17-3A-2] Congenital Muscular Dystrophy with Defective alpha-Dystroglycan Glycosylation; Lessons learned from Korean experience
Congenital muscular dystrophy (CMD) is genetically and phenotypically heterogeneous group of disorders, so that accurate genetic diagnosis is challenging even in the era of next generation sequencing. Among CMD, LAMA 2 related CMD (merosin deficient form) is more common in western countries, but in Asian, Collagen VI related CMD and alpha-dystroglycan defective CMDs are more common. Alpha-dystroglycanopathy is also a clinically and genetically heterogeneous group of muscular dystrophies characterized by defective glycosylation of alpha-dystroglycan. The hypoglycosylation of alpha-dystroglycan in skeletal muscle and brain leads to variable clinical features and the most frequently reported phenotypes include muscle-eye-brain disease, Walker-Walburg syndrome, and Fukuyama congenital muscular dystrophy. An increasing number of associated genes have been identified up to date: FKTN, FKRP, POMT1, POMT2, POMGnT1, LARGE, ISPD, GTDC2, B3GNT1, B3GALNT2, GMPPB, TMEM5, POMK, and DAG1. In this presentation, we report the clinical and mutational characteristics of congenital muscular dystrophy in our cohort, a tertiary single center in Korea , especially focusing on the defective alpha-dystroglycan glycosylation in. Thirty genetically confirmed alpha-dystroglycanopathy children from 26 unrelated Korean families were included: FKTN (n = 23) POMGnT1 (n = 3), GMPPB (n = 2), POMT1 (n = 1), and ISPD (n = 1). All patients with FKTN mutations showed various degree of mental retardation with a relevant brain MRI abnormality. Two patients with GMPPB mutation showed no abnormality in brain MRI but both had suffered from congenital cataracts. Four patients (2 cases with FKTN mutations and 2 cases with POMGnT1 mutations) in our cohort have undergone a retinal detachment surgery implying this ophthalmologic emergency is not rare in the patients with severe phenotypes. The ongoing identification of mutations and further studies regarding the clinical features of each mutation in the associated genes will provide better understanding of this rare group of inherited muscle diseases.