Apolipoprotein E genotype and cerebral palsy.

AIM: Apolipoprotein E (APOE, protein; [ApoE, gene]) is a lipid transport protein abundantly present in brain cells. We investigated whether the APOE genotype is associated with cerebral palsy (CP) and whether patients with CP with comorbid conditions and more severe neurological deficits are likely to have a particular genotype. METHOD: In a cross-sectional study, 243 individuals with spastic CP (135 males, 108 females; mean age at data collection 11 year ([SD 6y 7mo], 34% with hemiplegia, 37% with diplegia, 29% with triplegia/tetraplegia; 44% with mild motor involvement), 31% with moderate motor involvement, 25% with severe motor involvement, were compared with healthy individuals matched by age, race, and sex to analyse the association between APOE genotype and the incidence of CP. Associations between the APOE genotype and the incidence of comorbidities and neurological deficits were studied in the group with CP. RESULTS: The APOE epsilon2epsilon3 genotype was significantly more prevalent in the group with CP (11%) than the comparison group (5%) (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.01-7.66). The presence of the epsilon2 allele raised the probability of having CP (OR 3.2; 95% CI 1.27-8.27). The presence of ApoE epsilon4 was not significantly different among groups. No relation was found between APOE genotype and severity of neurological deficit or distribution of motor involvement. Four patients with CP presented the epsilon4epsilon4 genotype, and all exhibited epilepsy and microcephaly. Eleven of 12 individuals with CP and macrocephaly carried the epsilon3epsilon3 genotype. INTERPRETATION: A higher prevalence of the APOE epsilon2 genotype was found among those with CP. The association of microcephaly and epilepsy with the epsilon4epsilon4 genotype and the association of macrocephaly with epsilon3 demand further investigation.

Homozygosity enhances severity in spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3, or Machado-Joseph disease, is an autosomal dominant neurodegenerative disease characterized by a wide spectrum of clinical findings that include progressive cerebellar ataxia. All affected individuals have an expanded CAG repeat mutation in one allele of the ATXN3 gene. An inverse relationship exists between the age of onset and the number of repeats in the abnormal expanded allele. The case described is that of a child with Machado-Joseph disease, daughter of a consanguineous affected couple. She inherited the expanded allele in homozygosity with CAG repeat size similar to that of her parents, and had a distinct early onset (4 years of age) and severe clinical phenotype. This case supports the conclusion that homozygosity aggravates the clinical phenotype. Loss of function of the normal expressed ataxin-3, or possibly aggregation of ataxin-3, may be implicated in disease mechanism.