Childhood Absence Epilepsy with Tonic-Clonic Seizures and Electroencephalogram 3–4-Hz Spike and Multispike–Slow Wave Complexes: Linkage to Chromosome 8q24

Abstract

Childhood absence epilepsy (CAE), a common form of idiopathic generalized epilepsy, accounts for 5%-15% of childhood epilepsies. To map the chromosomal locus of persisting CAE, we studied the clinical and electroencephalographic traits of 78 members of a five-generation family from Bombay, India. The model-free affected-pedigree member method was used during initial screening with chromosome 6p, 8q, and 1p microsatellites, and only individuals with absence seizures and/or electroencephalogram 3-4-Hz spike- and multispike-slow wave complexes were considered to be affected. Significant P values of .00000-.02 for several markers on 8q were obtained. Two-point linkage analysis, assuming autosomal dominant inheritance with 50% penetrance, yielded a maximum LOD score (Zmax) of 3.6 for D8S502. No other locus in the genome achieved a significant Zmax. For five smaller multiplex families, summed Zmax was 2.4 for D8S537 and 1.7 for D8S1761. Haplotypes composed of the same 8q24 microsatellites segregated with affected members of the large family from India and with all five smaller families. Recombinations positioned the CAE gene in a 3.2-cM interval.

Long-term prognosis for childhood and juvenile absence epilepsy

“…Recent studies discovered two gene mutations in CAE probands with further epileptic or other neurological features [19,27] and several susceptibility loci [8,12,13,14,20,24,26,27] supporting genetic heterogeneity and the hypothesis of fundamental biological differences within IGE syndromes and even CAE subsyndromes. These findings may account for the different prognostic scenarios for a child with CAE, namely either entering remission of absences or evolving into other IGE syndromes (e. g. JME) either with later development of GTCS or myoclonic seizures or both [8,13,28,29].…”

Multiple exostoses, mental retardation, hypertrichosis, and brain abnormalities in a boy with a de novo 8q24 submicroscopic interstitial deletion

“…Of note is the fact that several forms of epilepsy have been mapped to 8q24, including childhood absence epilepsy (CAE; OMIM 600131), familial adult myoclonic epilepsy (MEBA; OMIM 601068), and benign neonatal epilepsy (EBN2; OMIM 121201) [DelgadoEscueta et al, 1999]. The CAE linkage interval has been defined between D8S1710 and D8S502 [Fong et al, 1998] and a strong candidate gene, the human homolog of the jerky mouse gene JH8, has been mapped into this interval [Morita et al, 1998]. However, both interval and JH8 are located distal of D8S1728, the marker defining the distal border of the deletion.…”

Linkage Analysis of Autopsy-Confirmed Familial Alzheimer Disease Supports an Alzheimer Disease Locus in 8q24

“…There are four different types of epilepsy mapped to 8q24 by linkage studies [71,72,73,74]. Earlier prospective cohort studies have noted a significantly higher incidence of seizures in AD patients than in nondemented elderly controls, with an up to 10-fold increased risk [75,76,77].…”