Familial adult myoclonic epilepsy: recognition of mild phenotypes and refinement of the 2q locus

Arch Neurol. 2012 Apr;69(4):474-81. doi: 10.1001/archneurol.2011.584.

Abstract

Background: Familial adult myoclonic epilepsy (FAME) is an autosomal dominant syndrome characterized by a core triad of cortical tremor, multifocal myoclonus, and generalized tonic-clonic seizures.

Objectives: To expand the phenotypic spectrum of FAME, to highlight diagnostic pointers to this underrecognized disorder, and to refine the FAME2 genetic locus.

Design: Observational family study.

Setting: The study was coordinated in a tertiary academic hospital, with data acquired in diverse primary, secondary, and tertiary care settings.

Participants: Consenting members of a single large family.

Results: A 6-generation FAME kindred of European descent was ascertained in New Zealand and Australia. Affected family members (N = 55) had fine hand tremor, with onset typically in adolescence (median age, 15 years; age range, 4-60 years). Proximal myoclonus was present in 44 of 55 (80%), arising later than hand tremor (median age, 17 years; age range, 5-60 years). Generalized tonic-clonic seizures occurred in 8 of 55 (15%), with a median age at onset of 43.5 years (age range, 18-76 years). Neurophysiological testing confirmed features of cortical reflex myoclonus. Genetic mapping narrows the FAME2 (OMIM 607876) locus on chromosome 2 to a 13.3-megabase interval, harboring 99 known protein-coding genes.

Conclusions: The most common FAME phenotype in this large family is mild postural hand tremor resembling essential tremor, combined with subtle proximal myoclonus. Generalized tonic-clonic seizures are uncommon and occur around sleep onset following severe generalized myoclonus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Child
  • Child, Preschool
  • Chromosome Mapping
  • Chromosomes, Human, Pair 2
  • Electroencephalography
  • Electromyography
  • Epilepsies, Myoclonic / complications*
  • Epilepsies, Myoclonic / genetics*
  • Evoked Potentials, Somatosensory / genetics
  • Family Health*
  • Female
  • Genetic Linkage*
  • Humans
  • Italy
  • Male
  • Memory Disorders / etiology*
  • Memory Disorders / genetics
  • Middle Aged
  • Phenotype
  • Recognition, Psychology / physiology*
  • Reflex / genetics
  • Tremor / etiology
  • Tremor / genetics
  • Young Adult