Leukoencephalopathy with Vanishing White Matter

Background and History: 

This is a rare, chronic, and unrelenting neurological disease involving primarily brain structures although the course is highly variable.

Clinical Correlations: 

The title for this condition likely applies to a group of disorders with common features but with variable age of onset and rates of progression.  In very young children normal milestones such crawling and walking may be the first signs of disease.  In patients with a later onset, the first signs are unsteady walking and a spastic, stiff gait.  The neurological deterioration is relentless but somewhat episodic.  Periods of stability are often interrupted by episodes of acute deterioration following head trauma or infections which may be of a relatively minor nature.  Patients may lapse into unconsciousness or extended periods of coma after witnessing frightening events.  A few patients have seizures.  Behavioral problems, psychiatric symptoms and dementia can occur.  Almost all patients have some cognitive disabilities and eventually become immobile.  Death can occur within a few years in patients with an early onset of symptoms but even older patients do not have a normal lifespan.

The optic nerve is often affected in this condition and it is not uncommon for blindness to occur.

Some females who live to puberty experience ovarian failure.

Genetics: 

This condition is inherited in an autosomal recessive pattern as the result of DNA mutations in one of at least five genes.  Parents who carry one mutation are clinically normal but children born to parents who each are carriers have a 1 in 4 chance that each child will inherit the two mutations and develop this disorder.

Diagnosis and Prognosis: 

Neurologists usually diagnosis this disorder based on the results of a clinical examination and an MRI.  There is no effective treatment for the neurological deterioration although seizures can sometimes be treated.  Lifespan is shortened in almost all patients.

Additional Information
Inheritance/Pedigree: 
Autosomal recessive