• E Andermann
  • Anna Jansen
  • A. Al-Asmi
  • C. Dobson-Stone
  • Anthony Monaco
  • A. Lang
  • Francine Robert
  • Amanpreet Badhwar
  • Suha Mercho
  • François Dubeau
  • Adrian Danek
  • Frederick Andermann
Rationale: 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).
Methods: 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.
Results: 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
d´ej`a vu, fear, palpitation and vertigo. Epilepsywas 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
Conclusions: 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)
Original languageEnglish
Pages (from-to)357-358
Number of pages2
Issue numbers7
Publication statusPublished - 2004
Event2004 Annual Meeting of the American Epilepsy Society - New Orleans, United States
Duration: 3 Dec 20047 Dec 2004

    Research areas

  • Epilepsy, Genetics, Chorea-acanthocytosis (CHAC)

ID: 2321312