Clinical genetic studies in benign childhood epilepsy with centrotemporal spikes

Abstract

SUMMARYPurpose: To accurately determine the frequency and nature of the family history of seizures in patients with benign childhood epilepsy with centrotemporal spikes (BECTS). Method: 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. Key Findings: 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. Significance: 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.

GRIN2A mutations cause epilepsy-aphasia spectrum disorders

“…Investigation of relatives up to three degrees of relatedness to probands with BECTS or the epilepsy-aphasia spectrum suggest that complex inheritance is most likely with febrile seizures being the most common phenotype in relatives of probands 3, 9 .…”

Structural abnormalities in benign childhood epilepsy with centrotemporal spikes (BCECTS)

“…In benign childhood epilepsy with centrotemporal spikes (BCECTS), the marked agespecific onset and remission of electroclinical features, comorbid behavioral and cognitive problems, and genetic predisposition strongly suggest altered brain maturation [1][2][3][4][5]. To further understand developmental disorders of this nature, magnetic resonance imaging (MRI) analysis techniques have been used to identify the microstructural alterations of the brain in children with idiopathic focal epilepsy including BCECTS [6][7][8].…”

Identification of new risk factors for rolandic epilepsy: CNV at Xp22.31 and alterations at cholinergic synapses

“…Both an autosomal-dominant model of inheritance of the EEG trait CTS8 and a complex mode of inheritance for seizure risk9 have been suggested. Loci for CTS have been identified at ELP4-PAX6 on 11p1310 11 and at 15q13 ( CHRNA7) 12.…”