Vanishing white matter disease associated with progressive macrocephaly

Vanishing white matter disease (VWM) is one of the most frequent inherited childhood leukoencephalopathies. Five genes have been implicated in this disease (EIF2B1-5), which encode the five subunits of translation initiation factor eIF2B. The disease has an autosomal recessive mode of inheritance. The age of onset and clinical severity vary widely. The diagnosis is based on magnetic resonance imaging (MRI) findings and is confirmed by molecular studies. We describe an affected female patient with a common and a novel mutation of the EIF2B5 gene, who demonstrated a progressive neurological and radiological deterioration. An unusual feature was her striking macrocephaly. She had an early clinical onset at two years of age and is currently still alive at 26 years of age.