Clinical And Molecular Genetic Study Of A Familiy With Familial Partial Epilepsy

ObjectiveThree forms of idiopathic partial epilepsy with autosomal dominant inheritance have been describled: (a) autosomal dominant nocturnal frontal lobe epilepsy(ADNFLE);(b) autosomal dominant lateral temporal lobe epilepsy(ADLTLE) or autosomal dominant partial epilepsy with auditory features(ADPEAF);and (c) familial partial epilepsy with variable foci(FPEVF). Here we describe a three-generation family with partial epilepsy. We performed clinical and molecular genetic study related to this family.MethodsEvery affected member of the family was carefully evaluated related to ictal semeiology, interictal active EEG, structural and functional neuroimaging, and neuropsychological tests, in order to acquire the complete clinical phenotype. Based on the progress reported in this field, we selected three genes(LGI1, CHRNA4, CHRNB2) as candidate genes, DNA sequencing was performed on all their exons and the exon-intron splicing sites.ResultsThe characteristics of this family are as follows: (1). there are 8 affected members in three generation, one male in the first generation, seven(2 male, 5 female) in the second generation. In the third generation, a male has epileptic abnormalities in EEG, however, he has no clinical seizures;(2). the onset age range from 26 to 43 years, median age is 32.5 years, mean age is 32.75±10.25 years;(3).all members had no febrile seizures;(4).there is no known history of any condition that could have caused seizures;(5).most seizures are during waking time;(6). seizure frequency in every affected member is relatively low, the course seems benign with only two members still having seizures occasionally;(7).AEDs responsiveness is good;(8).auditory aura is found in only one members, visualaura in three members, other auras including vertigo, head deviation, psychic symptoms, autonomic symptoms. Ictal semeiology and interictal active EEG abnormalities suggest temporal lobe origin, especially lateral temporal lobe in three members;(9).nueroimaging(MRI/CT) is normal, except for one member, demonstrating moderate cerebral atrophy and white matter dymyelination without definite relation to seizures;GOXseizures can be triggered in six members by twinkling, sleep deprivation, and/or fatigue;OD. most seizure type is simple partial or secondarily generalized tonic-clonic seizures(SGTCS). SGTCS is common(7/8), one member only has simple partial seizures;Q2). Neurological examination is normal. MMSE evaluation does not suggest intellectual impairment;(13). epileptic abnormalities in interictal active EEG are frequent, epileptic foci most locate in temporal lobe, however, some foci locate in parietal and occipital lobe. Light sleep tiggers epileptic discharge. Clinically diagnosis of ADLTLE and differential diagnosis of FPEVF type I are made.We carried out mutation screening of all exons and exon-intron splicing sites of the three candidate genes(LGIl, CHRNA4, CHRNB2). We do not find any mutations in these regions.Conclusions1. Genetic heterogeneity exists in this partial epilepsy family. We speculate there may exist other responsible gene related to ADPEAF syndrome. Linkage analysis may be an approach for new genes identification related to this syndrome.2. Clinical phenotype heterogeneity exists in this partial epilepsy family. Although clinical manifestation fulfills criteria of ADLTLE, diagnosis of FPEVF can not be excluded. Linkage study with genetic markers near 2q, and 22ql 1-12 can be carried out in order to confirm it.