Vanishing white matter disease
- Amy T Waldman, MD
Amy T Waldman, MD
- Assistant Professor of Child Neurology
- Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine
- Raphael Schiffmann, MD, MHSc
Raphael Schiffmann, MD, MHSc
- Medical Director of the Institute of Metabolic Disease
- Adjunct Professor of Biomedical Studies
- Baylor University Medical Center
- Section Editors
- Francisco González-Scarano, MD
Francisco González-Scarano, MD
- Section Editor — Multiple Sclerosis; Neurovirology & NeuroAIDS
- John P. Howe, III, MD, Distinguished Chair in Health Policy
- The University of Texas Health Science Center at San Antonio
- Marc C Patterson, MD, FRACP
Marc C Patterson, MD, FRACP
- Section Editor — Pediatric Neurology
- Professor of Neurology, Pediatrics, and Medical Genetics
- Chair, Division of Child and Adolescent Neurology
- Mayo Clinic College of Medicine
INTRODUCTION AND HISTORY
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" , a condition that is now recognized as a phenotypic variant of CACH/VWM . However, CACH/VWM was not recognized as a clinical syndrome until the 1990s.
●The disease was first recognized in 1992 . 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" .
●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 .
●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" .
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- INTRODUCTION AND HISTORY
- CLINICAL FEATURES
- Early childhood
- Late childhood/juvenile
- Headache and hemibody symptoms
- Genotype-phenotype correlations
- MRI criteria
- Genetic testing
- Laboratory testing
- Differential diagnosis
- SUMMARY AND RECOMMENDATIONS