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Leukoencephalopathy with Vanishing White Matter, Genetic Testing

Leukoencephalopathy with vanishing white matter (VWM) is a rare genetic disorder that affects the central nervous system, mainly the brain's white matter. It is a type of leukodystrophy, a group of disorders characterized by abnormalities in the brain's white matter.

Leukoencephalopathy with vanishing white matter genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).

Critical features of Leukoencephalopathy with vanishing white matter include:

  • Onset and Progression: Symptoms often begin early to mid-childhood, although onset can vary. The disease tends to progress slowly, with intermittent periods of rapid deterioration triggered by stressors such as infection or trauma.
  • Neurological Symptoms: Individuals with VWM may experience various neurological symptoms, including loss of motor skills, difficulty walking, muscle stiffness, spasticity, and difficulty coordinating movements.
  • Cognitive Impairment: Cognitive decline and intellectual disability can affect learning abilities and overall cognitive function.
  • Seizures: Seizures may occur in some individuals with VWM.
  • Neuroimaging Findings: Magnetic resonance imaging (MRI) of the brain typically reveals progressive destruction of the white matter, leading to atrophy. The white matter appears abnormal and may "vanish" or become cystic.
  • Genetic Basis: VWM is caused by mutations in specific genes, including the EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5 genes. These genes provide instructions for making components of the eukaryotic translation initiation factor 2B (eIF2B), which plays a role in cell protein synthesis.
  • Stress-Induced Deterioration: Stressful events, such as illness or injury, can trigger episodes of rapid neurological deterioration in individuals with VWM.

There is currently no cure for Leukoencephalopathy with vanishing white matter. Treatment is generally supportive and focused on managing symptoms and providing appropriate care. Physical and occupational therapy may be beneficial to help individuals maintain mobility and function.

Given the disorder's genetic nature, genetic counseling is important for affected individuals and their families. Understanding the disorder's genetic basis can provide insights into the risk of recurrence in future generations and inform family planning decisions.

More Information

Evanescent white matter leukoencephalopathy is a rare autosomal recessive disease that causes deterioration of the white matter of the central nervous system. It primarily affects mature oligodendrocytes and astrocytes. The disease is caused by mutations in different genes. One of the most common is EIF2B5, which codes for the epsilon subunit of the eIF2B protein, which is involved in protein synthesis.

The c.338G>A (p.Arg113His) variant is one of the most common and has been observed in patients with homozygosis and compound heterozygosis. The amino acid change results in a significant reduction in protein activity. This variant is present in the general population with a frequency of 0.03%.

The c.318A>T (L106H) variant is another of the most frequent pathogenic variants in patients with evanescent white matter leukoencephalopathy. This variant causes functional loss of the eIF2B subunit and prevents the formation of protein complexes with the other four subunits that make up eIF2B. A review study showed that all patients with the c.318A>T variant, both in homozygosis and heterozygosis, were associated with a slow chronic course of the disease. However, further studies are required to support this assumption.

The c.545C>T (T182M) variant is not as frequent as the previous one, but it has also been shown to be present in certain patients with late-onset disease. The presence of the variant could be associated with a milder form of leukoencephalopathy. However, further study is also required to confirm the association of the c.545CíT variant with milder forms of the disease.

Leukoencephalopathy with vanishing white matter genetic testing analyzes the 3 most frequent pathogenic mutations of the EIF2B5 gene.

The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).

Additional information
Results Time4 - 5 Weeks
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