Abstracts

Chorea-acanthocytosis (CHAC; OMIM 100500) is a neurodegenerative disorder characterized by the gradual onset of involuntary movements, dysarthria, areflexia, seizures, and dementia, and the presence of acanthocytes in peripheral blood smears. Seizures rarely constitute a predominant or presenting feature of the disease, and have been poorly described to date. In the majority of CHAC families, the disease is inherited as an autosomal recessive trait which maps to chr 9q21, and has recently been cloned (Rampoldi et al, 2001). We have studied 4 large French-Canadian kindreds with CHAC. Detailed medical and family histories, as well as medical records, of affected family members were obtained. Detailed biochemical tests and peripheral fresh blood smears for acanthocytes were performed. EEG, video-telemetry, MRI, volumetric and neuropsychological tests were carried out. Bloods were collected for DNA studies in 75 individuals. 11 patients in 6 sibships had clinical features of CHAC. 4 of the 6 sibships had clear parental consanguinity. 7 patients presented with epilepsy, 6 with confirmed temporal lobe epilepsy, years before developing involuntary movements including chorea, dysarthria, orofacial dyskinesia and unusual tics. The epileptic aura consisted of a sensation of déj[agrave] vu, fear, palpitation and vertigo.Epilepsy was intractable in most patients. Lamotrigine and carbamazepine worsened the involuntary movements. The patients had mood disorders and slowly progressive cognitive and memory dysfunction. EEG with video-telemetry confirmed ictal and interictal temporal epileptic abnormalities. Brain MRI showed caudate atrophy and abnormal signal in the basal ganglia. Peripheral blood smears showed acanthocytosis in all patients. Molecular tests ruled out Huntingdon disease, oculopharyngeal muscular dystrophy and MERRF. All 4 kindreds were homozygous for a large deletion mutation spanning exons 70-73 of the CHAC gene, and shared a common haplotype in the region. We describe 4 French-Canadian kindreds, three of which manifested familial mesial temporal lobe epilepsy as a presenting feature, delaying the diagnosis of CHAC. Parental consanguinity, the finding of a common haplotype and a shared deletion mutation, all suggest a founder effect. CHAC represents the first gene mutation associated with the clinical features of familial mesial temporal lobe epilepsy, to our knowledge. (Supported by an operating grant from CIHR to EA)