Familial adult myoclonic epilepsy (FAME): clinical features, molecular characteristics, pathophysiological aspects and diagnostic work-up.

Lorenz Peters,Stephan Klebe,Christel Depienne

doi:10.1515/medgen-2021-2100

Lorenz Peters, Stephan Klebe + Show 1 more

Open Access

https://doi.org/10.1515/medgen-2021-2100

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Abstract

Familial adult myoclonic epilepsy (FAME) is a rare autosomal dominant disorder characterized by myoclonus and seizures. The genetic variant underlying FAME is an intronic repeat expansion composed of two different pentamers: an expanded TTTTA, which is the motif originally present at the locus, and an insertion of TTTCA repeats, which is usually located at the 3' end and likely corresponds to the pathogenic part of the expansion. This repeat expansion has been identified so far in six genes located on different chromosomes, which remarkably encode proteins with distinct cellular localizations and functions. Although the exact pathophysiological mechanisms remain to be clarified, it is likely that FAME repeat expansions lead to disease independently of the gene where they occur. We herein review the clinical and molecular characteristics of this singular genetic disorder, which interestingly shares clinical features with other more common neurological disorders whose etiology remains mainly unsolved.

Highlights

Familial adult myoclonic epilepsy (FAME) is an autosomal dominant disorder characterized by a cortical myoclonic tremor and generalized seizures
The genetic variant underlying FAME is an intronic repeat expansion composed of two different pentamers: an expanded TTTTA, which is the motif originally present at the locus, and an insertion of TTTCA repeats, which is usually located at the 3′ end and likely corresponds to the pathogenic part of the expansion
Recent evidence suggests that the cause of FAME is linked to the same pathogenic repeat expansion in different genes and that the pathophysiological mechanisms are likely independent from the gene where the expansion occurs or its functions

Summary

Introduction

Familial adult myoclonic epilepsy (FAME) is an autosomal dominant disorder characterized by a cortical myoclonic tremor and generalized seizures. It was first described in 1990 in Japan [1] but has shown a worldwide distribution [2]. FAME symptoms usually occur in the second or third decade with a highly variable age of onset (range, 3–70 years) [2]. The defining symptom and most prominent movement disorder of FAME is cortical myoclonus. FAME2, seizures usually start a few years after myoclonus onset, whereas in patients with expansions in the MARCHF6 gene (FAME3), seizures may occur before or at the same time as cortical myoclonus in some family members [7].

16 TNRC6A

Findings

Conclusions