SNP Shot: Genomic Insights

CLCN2-related leukoencephalopathy is a brain disorder characterized by neurological issues that emerge from childhood to adulthood and generally remain stable. The most common symptom is impaired coordination and balance (ataxia), though most individuals can walk unaided. Many also experience frequent headaches. Children diagnosed with the condition often have learning disabilities, while adults typically develop vision problems. These vision problems stem from retinopathy (degradation of light-sensing tissue in the eyes) or optic nerve atrophy (degeneration of the nerves carrying visual information to the brain). Some individuals may experience mild muscle stiffness (spasticity), and affected males are usually infertile.

In rare cases, individuals with CLCN2-related leukoencephalopathy may experience dizziness (vertigo), ringing in the ears (tinnitus), hearing loss, episodes of abnormal movements (paroxysmal kinesigenic dyskinesia), or psychiatric disorders. However, the connection between these symptoms and CLCN2-related leukoencephalopathy is uncertain.

The neurological problems in CLCN2-related leukoencephalopathy arise from brain abnormalities, specifically leukoencephalopathy, which affects the brain's white matter. This white matter comprises nerve fibers insulated by myelin, a fatty substance crucial for rapid nerve impulse transmission. In affected individuals, the myelin becomes fluid-filled (edematous), disrupting the efficient transmission of nerve signals.

Inheritance:

CLCN2-related leukoencephalopathy follows an autosomal recessive inheritance pattern. This means that both copies of the CLCN2 gene in each cell must have mutations for the disorder to manifest. Individuals with the condition inherit one mutated copy of the gene from each parent, who are carriers of the mutation but typically do not exhibit symptoms themselves.