508P Clinical and genetic features of patients with myotonia congenita in Korea.

Myotonia congenita is a genetic muscle disorders characterized by muscle stiffness, pain, and non-dystrophic changes on muscle biopsy. It results from pathogenic variants in CLCN1. The condition manifests in early childhood, but symptoms can be variable. Most children are two or three years old when parents first notice their muscle stiffness, particularly in the legs, often triggered by sudden activity after rest. We investigated the clinical and genetic features of Korean patients with myotonia congenita. We conducted a retrospective review of medical records within the myopathy database from August 2002 to March 2024. Among the records examined, we identified 19 patients with pathogenic variants in CLCN1. Then, we analyzed the patient's clinical, laboratory, electrodiagnostic, and genetic findings. This study analyzed 19 patients from 16 unrelated families. A family history was positive in 14 (87.5%) unrelated families. Genetic analysis revealed that 11 unrelated families exhibited an autosomal dominant pattern, while three exhibited a recessive pattern, and two were sporadic cases. Among 19 patients, 14 (73.7%) were male and 5 (26.3%) were female. The median age of myotonia onset was 7 years [interquartile range: 4 – 13.5 years]. Myotonia was presented in all 19 patients. Muscle stiffness at the onset of exercise was present in 17 (89.5%) patients. Facial muscle involvement was noted in five (26.3%) patients. Grip myotonia was present in 15 (78.9%) patients, and warm-up phenomenon in 12 (63.2%) patients. Muscle hypertrophy in the lower leg was evident in three patients. The most common exacerbating factor was exertion (15/19, 89.5%). Creatine kinase levels were measured in 16 patients, and the median value was 159, with seven (43.8%) patients showing elevation above this value. Needle electromyography was performed in 17 patients, and myotonic discharges were observed in all cases. The most prevalent pathogenic variant of CLCN1 was c.892G>A, which was observed in six unrelated families (37.5%), followed by c.826G>T in two (12.5%). Additionally, the following variants were identified: c.566C>G, c.1297T>C, c.1063G>A, c.950G>A, c.1438C>T, c.2509-1G>A, c.949C>T, and c.962T>A, each in one family. Among them, c.826G>T and c.2509-1G>A were novel variants. Our study showed the clinical and genetic features of Korean patients diagnosed with myotonia congenita, contributing to the understanding of the manifestation and genetic basis of this disease. [ABSTRACT FROM AUTHOR]