Co-occurrence of the Gene ZNF9 Mutations (Myotonic Dystrophy Type 2) and Gene CLCN1 (Myotonia Congenita) in One Family – a Case Report

Summary

Myotonia is delayed skeletal muscle relaxation after voluntary contraction. It is associated with impaired chloride or, less frequently, sodium channels in the muscle membrane. The chloride channel defect may be caused by a primary mutation in the skeletal muscle chloride channel gene (CLCN1) or it is secondary as in myotonic dystrophy caused by post-transcription effect of accumulated ribonucleic acid, containing expanded triplets or tetraplets of the mutated gene, on the synthesis of chloride channels. Impaired muscle relaxation that occurs in childhood dominates in patients with congenital myotonia. Clinically, the myotonia is evident and is mitigated by moderate exercise (warmup phenomenon). On the contrary, muscle weakness and systemic symptoms are prominent in myotonic dystrophy, myotonia is is less apparent. Unlike the size of the expansion (myotonic dystrophy type 1), there is no evidence that homozygous state in myotonic dystrophy would be associated with poorer clinical course or an earlier onset of the disease. We present a rare case of a patient with decontraction disorder from 33 years of age. The objective neurological finding included mild pelvic girdle muscle weakness, significant action myotonia, percussion myotonia and positive warm-up phenomenon. Molecular genetic testing confirmed myotonic dystrophy type 2 with the expansion on both alleles of the ZNF9 gene, homozygous state was supported by examination of ancestors and their relatives. Concurrently, the patient is a carrier of a mutation in the semidominate CLCN1 gene that she acquired from her mother, a carrier of heterozygous mutations in the ZNF9 gene. Homozygous phenotype of the expansive autosomal dominant gene mutations (myotonic dystrophy) generally does not lead to more severe phenotype, this condition is probably due to a concurrent mutation in chloride channels.

Key words:
myotonia – myotonic dystrophy – congenital myotonia – molecular genetics

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manu­script met the ICMJE “uniform requirements” for biomedical papers.