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A Korean Kindred With Autosomal Dominant Nocturnal Frontal Lobe Epilepsy and Mental Retardation
Yong-Won Cho, MD;
Gholam K. Motamedi, MD;
Iris Laufenberg;
Sung-Il Sohn, MD;
Jeong-Geun Lim, MD;
Hyung Lee, MD;
Sang-Doe Yi, MD;
Ju-Hwa Lee, PhD;
Dae-Kwang Kim, MD;
Richard Reba, MD;
William D. Gaillard, MD;
William H. Theodore, MD;
Ronald P. Lesser, MD;
Ortrud K. Steinlein, MD
Arch Neurol. 2003;60:1625-1632.
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  4 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.
From the Departments of Neurology (Drs Cho, Lim, H. Lee, Yi, and J.-H. Lee) and Anatomy (Dr Kim), Keimyung University, Dongsan Medical Center, Taegu, and Department of Neurology, Eulji University School of Medicine, Daejeon (Dr Sohn), Republic of Korea; Departments of Neurology (Dr Motamedi) and Nuclear Medicine (Dr Reba), Georgetown University School of Medicine, Georgetown University Hospital (Dr Motamedi), and Children's National Medical Center (Dr Gaillard), Washington, DC; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md (Dr Theodore); Departments of Neurology and Neurosurgery, School of Medicine, and Zanvyl Krieger Mind/Brain Institute, The Johns Hopkins University, Baltimore, Md (Dr Lesser); and Institut für Humangenetik, Universitätsklinikum Bonn, Rheinische Friedrich Wilhelms–Universität, Bonn, Germany (Dr Steinlein and Ms Laufenberg).
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