Familial Partial Epilepsy with Variable Foci in a Dutch Family: Clinical Characteristics and Confirmation of Linkage to Chromosome 22q

Abstract

Summary:  Purpose: Three forms of idiopathic partial epilepsy with autosomal dominant inheritance have been described: (a) autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE); (b) autosomal dominant lateral temporal epilepsy (ADLTE) or partial epilepsy with auditory features (ADPEAF); and (c) familial partial epilepsy with variable foci (FPEVF). Here we describe linkage analysis in a Dutch four‐generation family with epilepsy fulfilling criteria of both ADNFLE and FPEVF. Methods: Clinical characteristics and results of EEG, computed tomography (CT), and magnetic resonance imaging (MRI) were evaluated in a family with autosomal dominantly inherited partial epilepsy with apparent incomplete penetrance. Linkage analysis was performed with markers of the ADNFLE (1p21, 15q24, 20q13.3) and FPEVF (2q, 22q11‐q12) loci. Results: Epilepsy was diagnosed in 10 relatives. Age at onset ranged from 3 months to 24 years. Seizures were mostly tonic, tonic–clonic, or hyperkinetic, with a wide variety in symptoms and severity. Most interictal EEGs showed no abnormalities, but some showed frontal, central, and/or temporal spikes and spike–wave complexes. From two patients, an ictal EEG was available, showing frontotemporal abnormalities in one and frontal and central abnormalities in the other. Linkage analysis with the known loci for ADNFLE and FPEVF revealed linkage to chromosome 22q in this family. Conclusions: The clinical characteristics of this family fulfilled criteria of both ADNFLE and FPEVF. The frequent occurrence of seizures during daytime and the observation of interictal EEG abnormalities originating from different cortical areas were more in agreement with FPEVF. The observed linkage to chromosome 22q supported the diagnosis of FPEVF and confirmed that this locus is responsible for this syndrome.