Congenital Myopathies: Characteristics and Subtypes in Hong Kong

Congenital myopathies are a group of childhood onset neuromuscular disorder with the diagnosis mainly based on genetic and pathological features. This is a unique group with phenotypic, genotypic and pathological heterogeneity, so the confirmation of an underlying diagnosis is often challenging. This is the first congenital myopathy case series in Hong Kong. A total of 15 patients have been diagnosed to have congenital myopathies with 11 patients had the genetic mutations being identified (4 patients had RYR1 mutations, 3 patients had ACTA1 mutations, 2 patients had KLHL40 mutations, 1 patient had MTM1 mutation and 1 patient had DNM2 mutation). There is genotypic heterogeneity as shown in our 5 patients with nemaline myopathies having different mutations including RYR1 (1 patient), ACTA1 (2 patients) and KLHL40 (2 patients) being identified. Pathological heterogeneity is also noted in our 4 patients with RYR1 mutations having different pathological features including nemaline rods, central cores, multi-minicores or only type 1 fiber predominance. The selective muscle involvement on muscle MRI provides clues to the underlying RYR1 mutations. Severe neonatal presentation with significant weakness that required early ventilation is common in our locality especially 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 spot mutation among Chinese patients.