Thursday July 6, 200611:30–13:30Hall 5CDiscussion Group SessionNon–age-related familial focal epilepsies: genotype-phenotype correlations

¹ A. Gambardella (   ¹ Università Magna Graecia, Italy )
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a recently identified partial epilepsy, which is characterized by brief frontal-lobe motor seizures occurring mostly during light sleep. The age of onset is usually infancy and adolescence, although seizures may start in adult life. Inheritance is autosomal dominant with 70% penetrance. The clinical picture of ADNFLE is relatively homogeneous, even if a broad range of severity has been observed even among affected members of the same pedigree. The interictal EEG is usually normal but ictal recordings show that these events are epileptic and appear to arise from the frontal lobes. Misdiagnosis as nightmares, night terrors, other parasomnias or even hysteria is common if clinicians are unaware of ADNFLE.
So far, ADNFLE has been associated with mutations affecting two genes coding for alfa4 and beta2 subunits of the neuronal nicotinic acetylcholine receptor (nAChR), which are located on chromosome 20q and chromosome 1 respectively. Moreover, although the gene has not yet been identified, another ADNFLE locus has been mapped to chromosome 15q24. More recently, there has been evidence that variations in the promoter of the corticotropic-releasing hormone gene may be also associated with ADNFLE. Nonetheless, the underlying gene has not yet been found in most ADNFLE families. Overall, these data support the pathogenic role of the cholinergic system in ADNFLE, even if its etiology appears to be the result of a variety of molecular defects despite the relative homogeneity of the clinical manifestations.