CHANNELOPATHIES AND RELATED DISORDERS: EP.227 Novel compound heterozygous mutations in CLCN1 in a patient with myotonia congenita

Abstract

Myotonia congenita (MC) is a rare hereditary chloride channel neuromuscular disorder. It caused by CLCN1 mutations which encodes chloride channel CLC1 for skeletal muscle. MC is characterized by transient muscle weakness, generalized muscle hypertrophy, non-progressive painless myotonia, and impaired muscle relaxation after contraction which resulting in muscle stiffness. We report a clinical case of an affected 14-year-old boy with athletic appearance due to generalized muscle hypertrophy, calf and brachial muscle stiffness, weakness especially in the legs, and normal deep tendon reflexes. He was born after uneventful pregnancy and delivery, with non-consanguineous marriage of his parents. There was no family history of neuromuscular disorders. He had numbness in the legs, getting tired quickly while walking, difficulties in starting voluntary activities such as walking and running. He had also delayed relaxation of hand grip after forceful holding. The neurological examination showed percussion-activated myotonia in the tongue, upper arms and legs. Plasma creatine kinase level was mildly elevated (200 UI/L, reference range: 0-190 UI/L), and transaminase levels were normal. We identified novel compound heterozygous mutations of CLCN1 [c.1673C>T (p.Pro558Leu) in exon 15, paternal and c.1886T>C (p.Leu629Pro) in exon 16, maternal] with next generation sequencing. Molecular genetic analysis is an accurate option for diagnosing MC. The present case expands the genotypic spectrum of MC.