Genetic architecture of idiopathic generalized epilepsy: clinical genetic analysis of 55 multiplex families.
Epilepsia
; 45(5): 467-78, 2004 May.
Article
en En
| MEDLINE
| ID: mdl-15101828
ABSTRACT
PURPOSE:
In families with idiopathic generalized epilepsy (IGE), multiple IGE subsyndromes may occur. We performed a genetic study of IGE families to clarify the genetic relation of the IGE subsyndromes and to improve understanding of the mode(s) of inheritance.METHODS:
Clinical and genealogic data were obtained on probands with IGE and family members with a history of seizures. Families were grouped according to the probands' IGE subsyndrome childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and IGE with tonic-clonic seizures only (IGE-TCS). The subsyndromes in the relatives were analyzed. Mutations in genes encoding alpha1 and gamma 2 gamma-aminobutyric acid (GABA)-receptor subunits, alpha1 and beta1 sodium channel subunits, and the chloride channel CLC-2 were sought.RESULTS:
Fifty-five families were studied. 122 (13%) of 937 first- and second-degree relatives had seizures. Phenotypic concordance within families of CAE and JME probands was 28 and 27%, respectively. JAE and IGE-TCS families had a much lower concordance (10 and 13%), and in the JAE group, 31% of relatives had CAE. JME was rare among affected relatives of CAE and JAE probands and vice versa. Mothers were more frequently affected than fathers. No GABA-receptor or sodium or chloride channel gene mutations were identified.CONCLUSIONS:
The clinical genetic analysis of this set of families suggests that CAE and JAE share a close genetic relation, whereas JME is a more distinct entity. Febrile seizures and epilepsy with unclassified tonic-clonic seizures were frequent in affected relatives of all IGE individuals, perhaps representing a nonspecific susceptibility to seizures. A maternal effect also was seen. Our findings are consistent with an oligogenic model of inheritance.
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Banco de datos:
MEDLINE
Asunto principal:
Familia
/
Epilepsia Generalizada
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Epilepsia
Año:
2004
Tipo del documento:
Article
País de afiliación:
Australia