Alexander Disease: Report of Two Unrelated Infantile Form Cases, Identified by GFAP Mutation Analysis and Review of Literature; The First Report from Iran

Background: Alexander disease (AD) is a sporadic leukodystrophy that predominantly affects infants and children and usually results in death within ten years after onset. The infantile form comprises the most of affected individuals. It presents in the first two years of life, typically with progressive psychomotor retardation with loss of developmental milestones, megalencephaly and frontal bossing, seizures, pyramidal signs and ataxia. The diagnosis is based on magnetic resonance imaging (MRI) findings and confirmed by GFAP gene molecular testing. GFAP gene encodes glial fibrillary acidic protein, is the only gene in which mutation is currently known to cause AD which is inherited in autosomal dominant manner.
Case Presentation: In this article we report the first two Iranian cases of infantile AD and their clinical, brain MRI and molecular findings. We report two novel mutations too in the GFAP gene that are associated with infantile form of AD.
Conclusion: GFAP gene mutations are a reliable marker for infantile AD diagnosed according to clinical and MRI defined criteria. A genotype-phenotype correlation had been discerned for the two most frequently reported GFAP gene mutations in infantile type of AD (R79 and R239), with the phenotype of the R79 mutations appearing much less severe than that of the R239 mutations. Our findings confirm this theory.

Keywords
Alexander Disease; Leukoencephalopathy; Alexander's leukodystrophy; Megalencephaly; Macrocephaly