Konjenital Miyopatilerin Klinik Özelliklerinin Değerlendirilmesi ve Genotip-Fenotip İlişkilerinin Belirlenmesi

Abstract

Congenital myopathies are a group of musculoskeletal disorders characterized by the presence of specific morphological features in skeletal muscle fibers, presenting with clinical or genetic heterogenicity, presenting with hypotonia or weakness at birth or early childhood. Recent advances in genetic research have made significant progress in understanding the pathophysiological mechanisms and increased accessibility to next-generation sequencing and whole exome sequencing. The definition of a specific genetic cause in a child with congenital myopathy is now becoming the gold standard in diagnosis, it will become increasingly important with the development of responsible gene specific therapies. Thanks to these developments, new perspectives have been introduced to the classification of congenital myopathies. The use of genetic classification instead of the histopathological classification used since the day it was defined. In our study, patients diagnosed as congenital myopathy; ages ranging from 3.2 to 31.7 years; 34 (54.8%) male and 28 (45.2%) female were evaluated by clinical and laboratory features, family history, age of diagnosis and waiting time until diagnosis, histopathological diagnosis and genetic analysis. The mean age at the time of diagnosis was 5.7 ± 4.6 (years) and the median waiting period was 31 months. Histopathologically, 13 (21%) of the patients had nemalin myopathy, 7 (11.3%) had core myopathy, 3 (4.8%) had centronuclear myopathy, 3 (4.8%) had CFTD, while 28 (45.2%) did not have specific diagnosis. Muscle biopsy is not procedured in 8 (12.9%) patients. Of the 37 patients, 6 (16.2%) had RYR1, 6 (16.2%) had TTN, 4 (10.8%) had NEB, 2 (5.4%) had PYROXD1, 1 (% 2,7) had MYH6, 1 (% 2,7) had KLHL40, 1 (% 2,7) had SEPN1, 1 (% 2,7) had TPM3, 1 (% 2,7) had ACTA1, 1 (% 2,7) had FBLN2, 1 (% 2,7) had FBLN5, 1 (% 2,7) had BTBD1, 1 (% 2,7) had SLC12A6, 1 (% 2,7) had SLC18A3, 1 (2.7%) had ATP2A1, 1 (2.7%) had TRIM54, 1 (2.7%) had AFG3L2, 1 (%2,7) had CCDC78, 1 (% 2,7) had COL6A3, 1 (% 2,7) had MYOT gene mutation, while the results of genetic analysis of 3 patients were negative. The genetic analysis process of 25 patients is still ongoing. In our study, we tried to obtain clinical clues to guide genetic analysis by comparing the clinical information of the patients with the results of genetic analysis.