The importance of combining multiple genetic techniques to define recessive forms of myotonia congenita

Myotonia congenita (MC) is a hereditary skeletal muscle disorder characterized by muscle stiffness at the beginning of exercise (i.e. myotonia), alleviated by repetition of contraction (ie. warm-up effect). MC is caused by mutations in the CLCN1 gene, encoding the skeletal muscle voltage-gated chloride channel (ClC-1) and is traditionally classified as Thomsen (autosomal dominant) and Becker (autosomal recessive) diseases. We report here an Italian patient affected by diffuse muscle hypertrophy, predominant in lower limb, neck, and trapezius and difficulty in getting up from a chair after prolonged rest, suggestive of recessive MC. The combination of a specific next-generation sequencing panel for skeletal muscle channelopathies and multiplex ligation-dependent probe amplification for CLCN1, leaded to the detection of the known missense mutation p.G482R and a novel deletion of the last 3 exons of the CLCN1. This report demonstrates the importance of combining multiple genetic techniques to define recessive forms of MC.