Alexander disease infantile form presenting with GFAP gene DNA mutation in exon 1 with substitution missense c.715C>T in p.R239C : a case report

Alexander disease is a rare disorder of the central nervous system caused by mutations in the gene for the glial fibrillaryacidic protein (GFAP). Since the disorder was first described in 1949, about 500 cases have been reported and more than 50 GFAP disease-causing mutations have been identified so far. We here report the case of a five-year-old Italian girl diagnosed with infantile form of Alexander disease after the identification, by molecular genetic analysis of the GFAP gene, of a c.715C>T (p.R239C) heterozygous missense substitution in exon 1. Such mutations are a very uncommon condition and have rarely been reported: only 18 cases has been described worldwide and, most of interest, no evidence of such mutation has been described throughout Italy. Our patient showed speech and neurological delays, ataxia, milestones regression, macrocephaly and wide base gait since she was 2 and a half years old. Magnetic resonance imaging reported frontal lobe white matter abnormalities. Brainstem auditory and visual evoked potentials were indicative of impaired bilateral central auditory and visual pathways. GFAP gene mutations have been previously determined as a cause infantile form of Alexander disease, but this kind of mutation represent a rare scenario, especially in Italy where it has never been described before. This case report could then contribute to the growing knowledge of Alexander Disease pattern worldwide, to more accurate genetic counseling and to provide further insight into the syndrome, especially with regard to the clinical features possibly associated with this kind of mutation.