OMIM ID:
Leukoencephalopathy with Vanishing White Matter
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Optic atrophy is a common feature and blindness is often the result.
Systemic Features
Onset of symptoms may occur at any time from 1.5 years of age to adulthood. Early psychomotor development may be normal but developmental milestones such as walking and crawling are often delayed. Patients with a later onset often have a milder course. Progression is chronic but often episodic with exacerbations following infection and blunt head trauma. Mental stress, even of a relatively minor nature such as fright, may likewise cause a worsening of symptoms. Such episodes can lead to loss of consciousness or even coma. Cerebellar ataxia and spasticity are common. Epilepsy may occur but is uncommon. Motor function is more severely impaired compared with mental deterioration. The MRI reveals a diffuse leukoencephalopathy as well as focal and cystic degeneration of white matter which may be present before the onset of symptoms. Cerebellar atrophy primarily involving the vermis is common. Behavioral problems, psychiatric symptoms, and even signs of dementia have been reported. The vast majority of patients have cognitive disabilities and many become severely handicapped and immobile. Early onset disease in children often leads to death within a few years whereas adults with later onset may live for many years.
Females with leukoencephalopathy who live to puberty may experience ovarian failure, a condition sometimes called ovarioleukodystrophy.
Genetics
Inheritance
This is an autosomal recessive disorder secondary to homozygous mutations in one of a group of five genes (EIF2B) located on chromosomes 1,2,3,12, and 14 encoding subunits of translation initiation factor 2B.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.