Epilepsy, Familial Adult Myoclonic, 3

For a phenotypic description and a discussion of genetic heterogeneity of familial adult myoclonic epilepsy, see FAME1 (601068).

Clinical Features

Depienne et al. (2010) reported a large French family in which 16 individuals had a form of myoclonic epilepsy. Most patients had onset as adults in their twenties or thirties, although 1 boy had onset of cortical myoclonus at age 10. Five patients presented with cortical myoclonus, 5 with seizures, and 6 with both at the same time. Two had only cortical myoclonus without seizures. Of the 14 with seizures, 11 had generalized tonic-clonic seizures and 3 had only focal seizures, characterized by visual hallucinations or transient loss of consciousness. Five patients met the electrophysiologic criteria for cortical myoclonus: paroxysmal polyspike and wave activity on EEG, photosensitivity, and recording of enlarged cortical components of somatosensory evoked potential, enhanced long-loop reflex (C-reflex), and cortical transients preceding the myoclonic jerks. Exercise, uneven ground, light, and low blood sugar precipitated the episodes. All patients responded to treatment. Seven patients were older than 60 years, and all had severe myoclonus affecting both upper and lower limbs, leading to walking impairment in 6. None had mental retardation or cognitive impairment.

Mapping

By genomewide linkage analysis of a large French family with cortical myoclonic epilepsy, Depienne et al. (2010) found linkage to a 9.31-Mb region on chromosome 5p15.31-p15.1 between D5S580 and D5S2096 (multipoint lod score of 3.66). Two asymptomatic family members also shared this region. The highest 2-point lod scores were 6.3 and 6.2 for D5S486 and D5S1380, respectively. Sequencing excluded mutations in the coding regions of the SEMA5A (609297) and CTNND2 (604275) genes.