Studying clinical and genetic characteristics of myopathies with early contracture

INTRODUCTION: Myopathies with early contracture are the heterogeneous hereditary muscle disorders characterized by early contractures and muscle weakness. The most common groups are Emery-Dreifuss muscular dystrophy (EDMD), Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). OBJECTIVE: In this study, the clinical and genetic characteristics of 50 patients from 31 unrelated families who followed up between 1989-2018 years at the Neuromuscular Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine were examined. RESULTS: The genetic cause of the myopathy with early contracture was found in 18 families (58%). Nineteen patients from eight unrelated families (25%) with EDMD-1, two patients from two families (6%) with EDMD-2, two patients from one family (3%) with EDMD-3, seven patients from seven families (22%) related collagen 6 were diagnosed. In EDMD-1 group, the mean onset age of disease was 5.5 ± 2.4 years, the most common initial sign was toe walking due to Achilles contracture. Scapuloperoneal muscle weakness distribution was the most common phenotypical feature. Cardiac involvement was observed in 90% of the patients during follow-up period and pace maker was implanted in 55% of the patients. Furthermore, 40% of female carriers had severe cardiac conduction defect. Four novel mutations were identified in the EMD gene c.416_417delTT; c.248_252delTACTC; c.19delC; Q44X [c.130C> T]). Although the number of OD-laminopathy patients were limited, the age of onset in EDMD-2 patients were earlier and symptoms were more severe than EDMD-1. Molecular examination revealed heterozygous mutation (c.1357C>T; c.127G>A) in two patients and homozygous novel mutation (c.71C> G) in one patient. Five of the patients in the collagen VI related myopathy group were BM, one was UCMD and one was OD collagen VI related LGMD phenotype. Four novel mutations were detected in the Col6A genes (c.838G>T; c.901-1G>C; c.6063+5G>A; c.8377_8379delGTC ). CONCLUSION: In our study, we detailed the clinical and genetic characteristics of myopathy patients with early contractures, as well as several novel mutations were identified.