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Childhood Ataxia with Central Nervous System Hypomyelination/Vanishing White Matter.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
2003 Feb 20 [updated 2012 Aug 09].

Excerpt

CLINICAL CHARACTERISTICS:

Childhood ataxia with central nervous system hypomyelination/vanishing white matter disease (CACH/VWM) is characterized by ataxia, spasticity, and variable optic atrophy. The phenotypic range includes a prenatal/congenital form, a subacute infantile form (onset age <1 year), an early childhood onset form (onset age 1-5 years), a late childhood /juvenile onset form (onset age 5-15 years), and an adult onset form. The prenatal/congenital form is characterized by severe encephalopathy. In the later onset forms initial motor and intellectual development is normal or mildly delayed followed by neurologic deterioration with a chronic progressive or subacute course. Chronic progressive decline can be exacerbated by rapid deterioration during febrile illnesses or following head trauma or major surgical procedures, or by acute psychological stresses such as extreme fright.

DIAGNOSIS/TESTING:

The diagnosis of CACH/VWM can be made with confidence in individuals with typical clinical findings, characteristic abnormalities on cranial MRI, and identifiable mutations in one of five genes (EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5), encoding the five subunits of the eukaryotic translation initiation factor 2B (eIF2B). Mutations have been found in approximately 90% of individuals with CACH/VWM using sequence analysis or mutation scanning.

MANAGEMENT:

Treatment of manifestations: Physical therapy and rehabilitation for motor dysfunction (mainly spasticity and ataxia); antiepileptic drugs for seizures. Prevention of secondary complications: Prevention of infections and fever when possible through the use of vaccinations, low-dose maintenance antibiotics during winter, antibiotics for minor infections, and antipyretics for fever. For children, wearing a helmet outside helps minimize the effects of head trauma. Surveillance: Close monitoring of neurologic status for several days following head trauma or surgical procedures with anesthesia. Agents/circumstances to avoid: Contact sports, head trauma, stressful situations including high body temperature.

GENETIC COUNSELING:

CACH/VWM is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once an at-risk sib is known to be unaffected, the chance of his/her being a carrier is 2/3. Prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing mutations in an affected relative have been identified.

Copyright © 1993-2015, University of Washington, Seattle. All rights reserved.

PMID:
20301435
[PubMed]
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