Clinical genetic studies in benign childhood epilepsy with centrotemporal spikes.
OBJECTIVE
To accurately determine the frequency and nature of the family history of seizures in patients with benign childhood epilepsy with centrotemporal spikes (BECTS).


METHODS
Participants with BECTS were recruited from the electroencephalography (EEG) laboratories of three pediatric centers and by referral. Pedigrees were constructed for up to three degrees of relatedness for each proband. All available affected and unaffected individuals underwent phenotyping using a validated seizure questionnaire. The proportion of affected relatives according to degree of relatedness was calculated and phenotypic patterns were analyzed.


RESULTS
Fifty-three probands with BECTS had a mean age of seizure onset at 7.8 years (range 2-12 years). Thirty-four (64%) of 53 patients were male. For 51 participants, pedigrees were available for three degrees of relatedness. Fifty-seven (2.7%) of 2,085 relatives had a history of seizures: Twenty-one (9.8%) of 214 first-degree, 15 (3%) of 494 second-degree, and 21 (1.5%) of 1,377 third-degree relatives. Febrile seizures were the most frequent phenotype, occurring in 26 of 57 affected relatives. There were 34 relatives with epilepsy: 6.5% (14 of 214) first-degree, 1.8% (9 of 494) second-degree, and 0.8% (11 of 1,377) third-degree relatives. Of 21 affected first-degree relatives: 8 of 21 had febrile seizures (FS), 4 had BECTS, 2 had epilepsy-aphasia spectrum disorder, one had temporal lobe epilepsy with hippocampal sclerosis, 2 had focal epilepsy of unknown cause, 2 had genetic generalized epilepsies, and 3 had miscellaneous.


CONCLUSIONS
The frequency of epilepsies in relatives and the heterogeneous syndromes observed suggest that BECTS has a genetic component consistent with complex inheritance. Focal epilepsies are the most common seizure disorder observed in relatives, especially BECTS and epilepsy-aphasia spectrum disorder. Additional acquired or environmental factors are likely to be necessary for expression of the seizure disorder.
Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Danya F
DF
Vears
Meng-Han
MH
Tsai
Lynette G
LG
Sadleir
Bronwyn E
BE
Grinton
Leasha M
LM
Lillywhite
Patrick W
PW
Carney
A Simon
AS
Harvey
Samuel F
SF
Berkovic
Ingrid E
IE
Scheffer
D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D019305:Epilepsy, Rolandic / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010375:Pedigree