Myotonia congenita associated to multiple sclerosis in a Tunisian family

Objectives The CLCN family of voltage-dependent chloride channel genes comprises nine members (CLCN1-7, Ka and Kb) which demonstrate quite diverse functional characteristics while sharing significant sequence homology. Here, we report a CLCN1 gene mutation associated to myotonia congenita and multiple sclerosis. Methods Neurological examinations, biological and electrophysiological investigations were offered to a female child suffering from learning difficulties and muscle weakness/hypertrophy as well as her parents who complain for infertility and were candidate for an artificial reproduction technique (ART) attempt. The diagnosis of myotonia congenita was suspected and molecular investigation of CLCN1 gene was conducted for the girl, her mother and her father who suffered from multiple sclerosis associated to stigmatas of non-dystrophic myotonias. Results A CLCN1 mutation was detected in the child and her non-consanguineous parents. Family history was apparently negative for neuromuscular diseases and ectrophysiological investigation in the parents did not show any muscle abnormality. Conclusion Molecular results were concordant with the recessive inheritance mode of the detected CLCN1 mutation in our Tunisian family. Genetic counseling provided to the non-consanguineous couple before ART was offered with multiple reservations. In fact, the non-consanguinity and the description of the same mutation in literature in association with the two forms of myotonia congenital: recessive and dominant forms were confusing. The association in the father of multiple sclerosis (MS) with the patient-reported clinical myotonia was also intriguing. Here, the heterouzygous CLCN1 mutation may be responsible of the clinical association underlying a unique channelopathy simultaneously involving the peripheral and the central nervous system.
Keywords: Myotonia congenita, multiple sclerosis, CLCCN1, ART genetic counselling