title: Familial adult myoclonic epilepsy: recognition of mild phenotypes and refinement of the 2q locus.
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.
  
  
  OBJECTIVE
  To expand the phenotypic spectrum of FAME, to highlight diagnostic pointers to this underrecognized disorder, and to refine the FAME2 genetic locus.
  
  
  METHODS
  Observational family study.
  
  
  METHODS
  The study was coordinated in a tertiary academic hospital, with data acquired in diverse primary, secondary, and tertiary care settings.
  
  
  METHODS
  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.
authors.affiliation: Institute of Genetic Medicine, Faculty of Medical Sciences and Newcastle Biomedicine, Newcastle University, Central Parkway, Newcastle upon Tyne, England. DECrompton@me.com
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Crompton
authors.forename: Lynette G
authors.initials: LG
authors.lastname: Sadleir
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Bromhead
authors.forename: Melanie
authors.initials: M
authors.lastname: Bahlo
authors.forename: Susannah T
authors.initials: ST
authors.lastname: Bellows
authors.forename: Todor
authors.initials: T
authors.lastname: Arsov
authors.forename: Rosemary
authors.initials: R
authors.lastname: Harty
authors.forename: Kate M
authors.initials: KM
authors.lastname: Lawrence
authors.forename: John W
authors.initials: JW
authors.lastname: Dunne
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D004569:Electroencephalography; D004576:Electromyography; D004831:Epilepsies, Myoclonic / Q000150:complications* / Q000235:genetics*; D005073:Evoked Potentials, Somatosensory / Q000235:genetics; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007558:Italy; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D021641:Recognition, Psychology / Q000502:physiology*; D012018:Reflex / Q000235:genetics; D014202:Tremor / Q000209:etiology / Q000235:genetics; D055815:Young Adult