Objective We report on a case with clinical phenotype suggesting Alexander disease in which the genetic testing – sequencing of the GFAP gene – provided no definitive conclusions.

Case presentation The proband is a 3 years-old boy who was referred to our department for epileptic seizures and psychomotor delay. The personal history revealed a normal psychomotor development till the age of 13 months when epileptic seizures occurred with partial response to antiepileptic drugs. A psychomotor regression was also observed, at actual presentation the boy presenting a development quotient of around 2 months. The clinical examination revealed also macrocephaly. Two cerebral MRI exams showed diffuse demyelization in fronto-insular white matter and striate nucleus bilaterally, with progressive aspect. The clinical and neuroimaging features are suggestive for Alexander disease and genetic testing (sequencing of GFAP gene) was indicated.

Results the genetic testing revealed a heterozygous variant in exon 1 of the GFAP gene, c.292G>C (p.Ala98Pro), previously unreported, which was interpreted as being of uncertain significance.

Conclusions In this case, the gene sequencing, although identified a variant of the gene, could not offer a clear result. New data (genetic testing of the parents, other cases with similar variant, functional studies) could bring further information about the clinical impact of this variant.