Familial adult myoclonic epilepsy: A new expansion repeats disorder

Abstract

Familial adult myoclonic epilepsy (FAME), also described with different acronyms (ADCME, BAFME, FEME, FCTE and others), is a high-penetrant autosomal dominant condition featuring cortical hand tremors, myoclonic jerks, and occasional/rare convulsive seizures. Prevalence is unknown since this condition is often under-recognized, but it is estimated to be less than 1/35,000. The disease usually starts in the second decade of life and has been genetically associated with at least 4 different loci (8q24, 2p11.1-q12.2, 5p15.31-p15 and 3q26.32-3q28). Recently, the expansion of non coding TTTTA and TTTCA repeats has been identified as the causative mutation in Japanese families linked to the 8q24. The diagnosis is supported by clinical features and electrophysiological investigations as jerk-locked back averaging, C-reflex, and somatosensory-evoked potential. Photic stimulation, emotional stress, and sleep deprivation may trigger both tonic-clonic and myoclonic seizures. FAME has a slow but progressive clinical course occurring with intellectual disability and worsening of both tremor and myoclonus although with a less severe decline compared to other progressive myoclonic epilepsies. Valproate, levetiracetam, and benzodiazepines are considered the first-line treatments.

Keywords: Cortical tremor; Epilepsy syndrome; Expansion repeats; Genetics; Myoclonus.