INTRODUCTION AND HISTORY
Vanishing white matter disease (VWM; MIM #603896), also known as childhood ataxia with central nervous system hypomyelination, leukoencephalopathy with vanishing white matter, and Cree leukoencephalopathy, is a chronic and progressive white matter disorder, often exacerbated by infection or head trauma.
Scattered neuropathologic case reports beginning in the 1960s were the earliest descriptions of the disease [1-8]. In 1988, a study from Canada described a severe infantile leukodystrophy in three Cree Indian villages termed "Cree leukoencephalopathy" , a condition that is now recognized as a phenotypic variant of VWM . However, VWM was not recognized as a clinical syndrome until the 1990s.
●A 1993 study from Germany described three children with normal early development who rapidly declined with progressive ataxia and spasticity, followed later by bulbar symptoms, optic atrophy, and seizures; brain magnetic resonance imaging (MRI) showed a diffuse hypodensity of the white matter similar to the signal of the ventricles .
●A 1994 report from the United States described four unrelated patients with progressive ataxic diplegia that was named "childhood ataxia with diffuse central nervous system hypomyelination" .
●In 1997, a study from the Netherlands described a cohort of nine children, including three affected sibling pairs, who had similar clinical, radiographic, and pathologic characteristics and were diagnosed with a "new leukoencephalopathy with vanishing white matter" .