Myoclonus, Familial, 2

A number sign (#) is used with this entry because of evidence that familial myoclonus-2 (MYOCL2) is caused by heterozygous mutation in the SCN8A gene (600702) on chromosome 12q13. One such family has been reported.

For a discussion of genetic heterogeneity of familial myoclonus, see MYOCL1 (614937).

Clinical Features

Wagnon et al. (2018) reported a 3-generation family in which 5 individuals had onset of isolated action-induced nonepileptic myoclonus affecting the upper limb in the first decade. Two patients were examined and the other 3 were reportedly affected with a similar disorder. The 2 patients had onset at age 5 and 7 years, and had no other neurologic findings, particularly no dystonia, seizures, or cognitive impairment. The disorder was nonprogressive. Electrophysiologic studies of 1 patient in the first decade showed evidence of subcortical origin, but not cortical origin. The 35-year-old proband reported that the myoclonus was responsive to alcohol, suggesting cerebellar involvement.

Inheritance

The transmission pattern of MYOCL2 in the family reported by Wagnon et al. (2018) was consistent with autosomal dominant inheritance.

Molecular Genetics

In 3 affected members of a family with MYOCL2, Wagnon et al. (2018) identified a heterozygous missense mutation in the SCN8A gene (P1719R; 600702.0012). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family in those who agreed to testing. In vitro functional expression studies in transfected neuron-derived cells showed that the mutation caused a partial loss of function, manifest as decreased inward sodium current compared to controls.