FAME 3: a novel form of progressive myoclonus and epilepsy.
BACKGROUND
Familial adult myoclonic epilepsy (FAME) is associated with myoclonus, tremor, and rare seizures, and is a nonprogressive disorder linked to the FAME 1 locus. A similar disorder has been linked to the FAME 2 locus.


METHODS
Seventeen patients from two families with myoclonus and epilepsy were evaluated clinically and underwent EEG, EMG, jerk-locked averaging, and MRI scanning. Three had responses to magnetic stimulation assessed. Linkage was assessed for microsatellite markers across the FAME 1 and 2 loci.


RESULTS
The median age at onset was 20 years, with many patients having frequent seizures, cognitive impairment, and cerebellar dysfunction. Electrophysiologic features of cortical myoclonus were typically present, but photosensitivity was uncommon. MRI frequently demonstrated cerebellar atrophy. Pathology of a single case showed Purkinje cell loss, dentate atrophy, and neuronal loss and gliosis in the olives and pallidum. Analysis of genotypes for markers at the FAME 1 and FAME 2 loci excluded these as the region containing the same locus in one family, but only the FAME 2 locus was excluded in the other family.


CONCLUSIONS
This form of familial adult myoclonic epilepsy does not show linkage to either of the known familial adult myoclonic epilepsy loci, and is characterized in some members by frequent seizures, cerebellar ataxia, dementia, and progression of the disease. This may represent a new form of progressive myoclonus and epilepsy, which we have termed familial adult myoclonic epilepsy type 3.
Carr
J A
JA
Division of Neurology, Faculty of Health Sciences, University of Stellenbosch, South Africa. jcarr@sun.ac.za
van der Walt
P E
PE
Nakayama
J
J
Fu
Y-H
YH
Corfield
V
V
Brink
P
P
Ptacek
L
L
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001284:Atrophy; D001921:Brain / Q000473:pathology; D002524:Cerebellar Ataxia / Q000235:genetics / Q000473:pathology; D003072:Cognition Disorders / Q000453:epidemiology / Q000235:genetics; D018450:Disease Progression; D004401:Dysarthria / Q000235:genetics; D004569:Electroencephalography; D004576:Electromyography; D004831:Epilepsies, Myoclonic / Q000145:classification / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D004830:Epilepsy, Tonic-Clonic / Q000235:genetics; D005071:Evoked Potentials; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005911:Gliosis / Q000473:pathology; D006801:Humans; D008126:Lod Score; D008279:Magnetic Resonance Imaging; D008297:Male; D018895:Microsatellite Repeats; D009759:Nystagmus, Pathologic / Q000235:genetics; D010375:Pedigree; D011689:Purkinje Cells / Q000473:pathology; D013019:South Africa; D050781:Transcranial Magnetic Stimulation