Congenital Myopathies are a Group of Phenotypically and Genetically Heterogeneous Diseases

Abstract

Congenital myopathies are a group of childhood-onset neuromuscular disorder diagnosed by specific clinical, pathological, and genetic features. With the phenotypic, genotypic, and pathological heterogeneity of these specific conditions, diagnostic confirmation is often challenging. Among our 16 patients with the pathological findings of congenital myopathies, 11 have confirmed genetic mutations. Four patients have RYR1 mutations, three patients have ACTA1 mutations, two patients have KLHL40 mutations, one patient has MTM1 mutation, and one patient has DNM2 mutation. Genetically heterogeneity is well illustrated in the five patients with nemaline myopathy having different mutations including RYR1 (1 patient), ACTA1 (2 patients), and KLHL40 (2 patients). Pathological heterogeneity is nicely demonstrated in the four patients with confirmed RYR1 mutations but having different pathological features including nemaline rods, central cores, multi-minicores or type 1 fibre predominance. The specific finding of rectus femoris sparing on muscle magnetic resonance imaging provides helpful clues to the underlying RYR1 mutations. Neonatal onset of severe weakness requiring early ventilation is common in our cohort in patients with ACTA1 autosomal dominant mutation, KLHL40 autosomal recessive mutation, DNM2 autosomal dominant mutation, and MTM1 X-linked mutation. The missense RYR1 mutation (c.3523G>A) was found in two patients, and the missense KLHL40 mutation (c.1516A>C) was found in another two patients, suggesting that these variants could probably be the hot spots mutations among Chinese patients.