Neonatal Alexander disease : novel GFAP mutation and comparison to previously published cases

Abstract

<div lang="en" class="abs"><p class="abs_header">Abstract</p><p>Alexander disease (AxD) is a genetic leukodystrophy caused by <em>GFAP</em> mutations leading to astrocyte dysfunction. Neonatal AxD is a rare phenotype with onset in the first month of life. The proband, belonging to a large pedigree with dominantly inherited benign familial neonatal epilepsy (BFNE), had a phenotype distinct from the rest of the family, with hypotonia and macrocephaly in addition to drug-resistant neonatal seizures. The patient deteriorated and passed away at 6 weeks of age. The pathological and neuroimaging data were consistent with the diagnosis of AxD. Genetic analysis of the proband identified a novel de novo <em>GFAP</em> missense mutation and a <em>KCNQ2</em> splice site mutation segregating with the BFNE phenotype in the family. The <em>GFAP</em> mutation was located in the coil 2B region of GFAP protein, similar to most neonatal-onset AxD cases with an early death. The clinical and neuroradiological features of the previously published neonatal AxD patients are presented. This study further supports the classification of neonatal-onset AxD as a distinct phenotype based on the age of onset.</p></div>