P.42 - Congenital muscular dystrophy in Taiwan: a referral center experience

Abstract

Congenital muscular dystrophy (CMD) is a heterogeneous disease entity. The detailed clinical manifestation and causative gene for each subgroup of CMD are quite variable. This study aims to analyze the phenotypes and genotypes of Taiwanese patients with CMD as the epidemiology of CMD varies among populations and has been scantly described in Asia. A total of 48 patients suspected to have CMD were screened and categorized by histochemistry and immunohistochemistry studies. Different genetic analyses, including next-generation sequencing (NGS), were used. We identified 17 patients with sarcolemma-specific collagen VI deficiency (SSCD), 6 patients with merosin deficiency, two with reduced alpha-dystroglycan staining, and two with striking lymphocyte infiltration in addition to dystrophic change on muscle pathology. Fourteen in 15 patients with SSCD whose DNA were available, were shown to have COL6A1, COL6A2 or COL6A3 mutations by NGS analysis; all presented with marked distal hyperlaxity and normal intelligence. All six patients with merosin deficiency carried mutations in LAMA2. The clinical features were relatively uniform that were compatible with previous studies, except for higher proportion of mental retardation with epilepsy. With reduced alpha-dystroglycan staining, one patient was found to carry mutations in POMT1 while another patient carried mutations in TRAPPC11. LMNA mutations were found in the two patients with inflammatory change on muscle pathology. They were clinically characterized by neck flexion limitation and early joint contracture, but no cardiac problem had developed yet. Our study showed that muscle pathology remains helpful in guiding further molecular analyses by direct sequencing of certain genes or by target capture/NGS as a second-tier diagnostic tool, and is crucial for establishing the genotype-phenotype correlation. We also determined the frequencies of the different types of CMD in our cohort which is important for the development of a specific care system for each disease.