SNP Shot: Genomic Insights

Leukoencephalopathy with vanishing white matter (VWM) is a progressive disease primarily affecting the brain and spinal cord, which together form the central nervous system. VWM leads to the breakdown of the brain and spinal cord's white matter. This white matter is composed of nerve fibers insulated by a fatty substance called myelin, crucial for nerve protection and function.

Typically, individuals with VWM do not exhibit symptoms at birth. Affected children might experience slightly delayed motor skill development, such as delays in crawling or walking. As they enter early childhood, most develop motor problems, including muscle stiffness (spasticity) and coordination difficulties (ataxia). Cognitive decline may occur, but it's usually less severe than the motor impairments. Some affected females may experience abnormal ovarian development (ovarian dysgenesis). Distinctive brain changes, detectable through magnetic resonance imaging (MRI), are a hallmark of VWM and can be observed even before symptoms appear.

Although childhood onset is the most frequent form of VWM, severe cases can be present at birth. Cree leukoencephalopathy is a particularly severe, early-onset form observed in the Cree and Chippewayan populations of Quebec and Manitoba. In milder forms, symptoms may not manifest until adolescence or adulthood, with behavioral or psychiatric issues being the initial indicators. Adolescent females with milder forms of VWM may also experience ovarian dysfunction. This specific presentation is known as ovarioleukodystrophy.

VWM progression is usually characterized by fluctuating periods of stability interspersed with periods of rapid decline. Individuals with VWM are highly susceptible to stressors like infections, minor head injuries, or even severe fright. These stressors can trigger the onset of symptoms or exacerbate existing ones, potentially leading to lethargy or coma.

Inheritance:

VWM is inherited in an autosomal recessive manner. This means that an individual must inherit a mutated copy of the responsible gene from each parent. The parents, who each carry one copy of the mutated gene, usually do not display any signs or symptoms of the condition themselves.