GENETIC LANDSCAPE OF CONGENITAL MUSCULAR DYSTROPHIES(CMD) FROM CENTRAL AEGEAN PART OF TURKEY

OBJECTIVES: Congential muscular dystrophies(CMDs) are a group of genetically hetereogenous neuromuscular disorders involving distinct core phenotypes with variable prognosis.The main goal of our study is to identify the genotype-phenotype spectrum of CMDs in central Aegean part of Turkey.

MATERIALS and METHODS: The subjects registered from 2010 to 2020 to the pediatric neurology department of Dokuz Eylul University were enrolled.Regarding recent classifications the patients were described as follows:(a) definite core phenotypes with genetic analysis (b) probable core phenotypes with evidence of elevated CK levels and/or dystrophic patern on muscle biopsy (c) unclassified other CMDs.

RESULTS: We identified 71 subjects(37 male,34 female) from 62 unrelated families.Confirmed genetic diagnosis and consanguinity rate were 73 %(n=52) and 61 %(n=34) respectively.The most common presenting symptom was early onset muscle weakness.The most common phenotype was alfa-dystroglycanopathies(n=23) followed by COL6-RD(n=13) and LAMA2-RD(n=9).Other relatively common phenotypes were LMNA related CMD(n=5),SEPN1 related myopathy(n=4) and megaconial(CHKB,n=4) CMDs. Among alfa-dystroglycanopathies in our cohort,MEB/FCMD was the most common subtype with structural brain abnormalities and eye involvement.POMGnT1 was the most common mutated gene.

CONCLUSION: In contrast to population based studies in Europe, alfa-dystroglycanopathies are the most common phenotype in Turkey and c.1814 G>A mutation in POMGnT1 is frequent in Turkish population suggesting a founder effect. References: 1- Zambon AA, Muntoni F. Congenital muscular dystrophies: What is new?. Neuromuscular Disorders, 2021, 31.10: 931-942. 2. Sframeli M, Sarkozy A, Bertoli M et al. Congenital muscular dystrophies in the UK population: Clinical and molecular spectrum of a large cohort diagnosed over a 12-year period. Neuromuscular Disorders,2021,27(9):793-803.
Keywords: hypotonia, dystrophy, scoliosis, congenital, creatine kinase