A Korean kindred with autosomal dominant nocturnal frontal lobe epilepsy and mental retardation.
BACKGROUND
A Korean family had distinctive clinical and neuroimaging features and carried the same genetic mutation that was found in a previously described Japanese kindred with autosomal dominant nocturnal frontal lobe epilepsy.


OBJECTIVE
To describe the first Korean family with autosomal dominant nocturnal frontal lobe epilepsy.


METHODS
Members of a large family, including 9 affected individuals from 3 generations, underwent a comprehensive genetic, clinical, electroencephalographic, neuropsychological, and neuroimaging evaluation. Affected members were tested for possible mutations in transmembrane regions 1 through 3 of the neuronal nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) by direct sequencing and subsequent restriction analysis.


RESULTS
Seizures began in childhood, presenting as nocturnal episodes of staring, confusion, shouting, perioral movements, unintelligible speech, and hand waving. Some patients had ictal or interictal epileptiform activity in the temporal and/or frontocentral areas. Neurological examination and brain magnetic resonance imaging results showed no abnormalities, except that all patients available for testing had mild to moderate mental retardation. Fluorodeoxyglucose F 18 with positron emission tomography showed mild decreased glucose uptake in the superior and middle frontal regions, more so on the left than on the right. Patient response to carbamazepine was poor. All affected members were heterozygous for the CHRNA4 Ser252Leu mutation.


CONCLUSIONS
Disorders associated with mutations in the transmembrane region 2 of CHRNA4 are genetically and phenotypically heterogeneous. Distinctive features of this kindred include (1) mental retardation in all affected members available for testing, (2) abnormal brain findings on fluorodeoxyglucose F 18 with positron emission tomography, (3) poor response to carbamazepine, and (4) full penetrance.
Cho
Yong-Won
YW
Department of Neurology, Georgetown University Hospital, Washington, D.C. 20007, USA.
Motamedi
Gholam K
GK
Laufenberg
Iris
I
Sohn
Sung-Il
SI
Lim
Jeong-Geun
JG
Lee
Hyung
H
Yi
Sang-Doe
SD
Lee
Ju-Hwa
JH
Kim
Dae-Kwang
DK
Reba
Richard
R
Gaillard
William D
WD
Theodore
William H
WH
Lesser
Ronald P
RP
Steinlein
Ortrud K
OK
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D017034:Epilepsy, Frontal Lobe / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008607:Intellectual Disability / Q000150:complications* / Q000235:genetics*; D007723:Korea; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests; D010375:Pedigree; D019683:Penetrance; D011978:Receptors, Nicotinic / Q000235:genetics; D014055:Tomography, Emission-Computed
D011978:Receptors, Nicotinic