Autosomal dominant nocturnal frontal lobe epilepsy: An electroclinical study of a Norwegian family with ten affected members

Purpose: The aim of the study was to describe in detail the electroclinical findings associated with a mutation in the acetylcholine receptor in a Nor wegian family with autosomal dominant nocturnal frontal lobe epilepsy (ADNF LE). Furthermore, we compared the clinical features associated with this mu tation with those of an Australian family with a different mutation at the same locus, as well as with those of eight Italian families with ADNFLE and without a verified mutation in this gene. Methods: We obtained medical records from all of the 10 known affected memb ers of the Norwegian family. A personal interview and a clinical neurologic examination were carried out in six of them. Interictal and ictal scalp EE G recordings were obtained in eight and three, respectively, computed tomog raphy/magnetic resonance imaging (CT/MRI) in five, and blood samples for ge netic analysis in seven individuals. The clinical features after an inserti on of a leucine residue in the alpha 4 subunit of the neuronal nicotinic ac etylcholine receptor are examined. Furthermore, the clinical features that accompany this insertion and the clinical features associated with a missen se mutation (Ser248Phe) in the same gene were compared. Results: All the affected individuals had a seizure semiology consistent wi th frontal lobe seizures. Their seizures started in childhood (mean age, 8 years) and were often misinterpreted as benign nocturnal parasomnias, noctu rnal paroxysmal dystonia, or a psychiatric disorder. The affected family me mbers were of normal intellect and showed no abnormalities at neurologic an d neuroradiologic examinations. Interictal scalp EEG registrations were mos tly normal, ictal scalp EEG registrations in three individuals revealed lef t frontal low-voltage epileptiform discharges in two, and only shallow arou sal preceding the attack in one. Although the seizure susceptibility varied among the affected individuals, the epilepsy course was mostly benign. Conclusions: Patients with ADNFLE, either with the 776ins3 mutation or the Ser248Phe mutation, and those without any recognized mutation in the acetyl choline receptor, have strikingly homogeneous phenotypes, and it seems diff icult to separate them on clinical grounds.