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Vanishing white matter disease

Raphael Schiffmann, MD, MHSc
Section Editors
Francisco González-Scarano, MD
Marc C Patterson, MD, FRACP
Deputy Editor
John F Dashe, MD, PhD


Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease (CACH/VWM; MIM #603896), also known as myelinopathia centralis diffusa, 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" [9], a condition that is now recognized as a phenotypic variant of CACH/VWM [10]. However, CACH/VWM was not recognized as a clinical syndrome until the 1990s.

The disease was first recognized in 1992 [11]. A detailed 1994 report from the United States described four unrelated patients with progressive ataxic diplegia and characteristic MRI features that was named "childhood ataxia with diffuse central nervous system hypomyelination" [12].

A 1993 study from Germany identified similar features in three children with normal early development who rapidly declined with progressive ataxia and spasticity, followed later by bulbar symptoms, optic atrophy, and seizures; brain MRI showed a diffuse hypodensity of the white matter similar to the signal of the ventricles [13].

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" [14].

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Literature review current through: Nov 2017. | This topic last updated: Oct 06, 2017.
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