Co-existence of CLCN1 and DNM2 variants in a phenotype overlapping myotonia and myopathy.
Fatemeh Sadat Haghighi, Seyed Mehdi Kalantar, Nasrin Ghasemi et al.
✦ AI-curated · Sources linked
Case in brief
An Iranian family was evaluated for a phenotype combining severe myotonia and myopathic features. The index patient had clinical and electrical myotonia, with myopathic changes on electromyography. Genetic testing identified two CLCN1 variants in a compound heterozygous state, consistent with recessive myotonia congenita. A heterozygous DNM2 p.Asp721Asn variant of uncertain significance was also found in three affected brothers with myopathic features. The CLCN1 findings support the myotonia diagnosis; whether the DNM2 variant contributes to the myopathy remains unresolved.
What made this case unusual
The overlapping phenotype was associated with compound heterozygous CLCN1 variants and a co-occurring DNM2 variant of uncertain significance in affected brothers, raising—but not establishing—the possibility of a genetic contribution to both myotonia and myopathy.
Diagnostic / clinical pearl
When myotonia and myopathic features coexist, comprehensive genetic evaluation may identify variants relevant to distinct components of the phenotype; a variant of uncertain significance should not be treated as causal without further evidence.