A new form of childhood onset, autosomal recessive spinocerebellar ataxia and epilepsy is localized at 16q21-q23

• Published in: Brain (London, England : 1878) Vol. 130; no. 7; pp. 1921 - 1928
• Main Authors: Gribaa, M., Salih, M., Anheim, M., Lagier-Tourenne, C., H'mida, D., Drouot, N., Mohamed, A., Elmalik, S., Kabiraj, M., Al-Rayess, M., Almubarak, M., Bétard, C., Goebel, H., Koenig, M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-07-2007; Oxford Publishing Limited (England)
• Subjects: Adolescent; Biochemistry, Molecular Biology; Biological and medical sciences; Biopsy; Brain; Brain - pathology; Child; Child, Preschool; Chromosome Mapping; Chromosomes, Human, Pair 16; Chromosomes, Human, Pair 16 - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Electroencephalography; Epilepsy, Tonic-Clonic; Epilepsy, Tonic-Clonic - genetics; Epilepsy, Tonic-Clonic - pathology; Female; Genotype; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Homozygote; Humans; Intellectual Disability - genetics; Intellectual Disability - pathology; Life Sciences; Magnetic Resonance Imaging; Male; Medical sciences; Mental Retardation; Microscopy, Electron; Molecular biology; Nervous system (semeiology, syndromes); Neurology; Pedigree; Quadriceps Muscle; Quadriceps Muscle - ultrastructure; Spinocerebellar Ataxias; Spinocerebellar Ataxias - genetics; Spinocerebellar Ataxias - pathology; Vacuoles; Vacuoles - ultrastructure; brain imaging; epilepsy; ataxia; homozygosity mapping; Cartography; Nervous system diseases; Spinocerebellar ataxia; Epilepsy; Central nervous system disease; Degenerative disease; Homozygosity; Cerebral disorder; Genetic disease
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awm078

Childhood ataxias are a complex set of inherited disorders. Ataxias associated with generalized tonic-clonic epilepsy are usually included with the progressive myoclonus epilepsies (PME). Five disease entities, Unverricht-Lundborg disease, Lafora's disease, neuronal ceroid lipofuscinoses, myoclonic epilepsy with ragged red fibres and sialidoses, account for the majority of PME cases. Two rare forms of ataxia plus epilepsy, sensory ataxic neuropathy, dysarthria and ophthalmoparesis, and infantile onset spinocerebellar ataxia were described recently and found to be caused by defective mitochondrial proteins. We report here a large consanguineous family from Saudi Arabia with four affected children presenting with generalized tonic-clonic epilepsy, ataxia and mental retardation, but neither myoclonus nor mental deterioration. MRI and muscle biopsy of one patient revealed, respectively, posterior white matter hyperintensities and vacuolization of the sarcotubular system. We localized the defective gene by homozygosity mapping to a 19 Mb interval in 16q21-q23 between markers D16S3091 and D16S3050. Linkage studies in this region will allow testing for homogeneity of this novel ataxia-epilepsy entity.