Chloride Channel Mutations Leading to Congenital Myotonia

Congenital myotonia is a non-dystrophic musculoskeletal disease that causes abnormal muscle relaxation. The prevalence of congenital disorders is notably high in Iran, emphasizing the importance of genetic assessment in suspicious cases. In this study, we aim to report cases with the chloride channel gene, CLCN1, mutations leading to significant morbidity. This case report study investigated four patients from four families with clinically defined congenital myotonia. Inclusion criteria were increased creatinine kinase (CK) and muscle stiffness. We collected data regarding family history, age of onset, and current therapeutic plan. All patients underwent skeletal muscle electromyography, cardiological evaluation, spirometry study, and hematochemistry assessment, including but not limited to muscle enzyme levels. Afterward, DNA was extracted from peripheral blood. Subsequently, whole exome sequencing (WES) and Sanger sequencing were done to detect and confirm variants, respectively. Age of onset ranged from 1 to 12 years in these patients, which are years apart from their first visit to the clinic. The warm-up phenomenon was present in all of them. A variant of uncertain clinical significance was found. We recommend that future research projects should study the efficiency of collaboration between clinicians, molecular geneticists, and other healthcare providers in order to find out about unclear variants as quickly as possible.