SNP Shot: Genomic Insights

Alexander disease is an uncommon neurological condition belonging to a group of disorders called leukodystrophies. Leukodystrophies, including Alexander disease, are characterized by the breakdown of myelin, the protective fatty layer around nerve fibers. Myelin is essential for the fast and efficient relay of nerve signals. When myelin is damaged, as in Alexander disease, nerve impulses are disrupted, leading to impaired nervous system function.

The most common form of Alexander disease is the infantile form, which typically begins before the age of 2. Infants with this form often exhibit an abnormally large brain and head (megalencephaly), seizures, muscle stiffness (spasticity), intellectual disability, and delayed development. While less common, the disease can also appear later in childhood (juvenile form) or in adulthood. Juvenile and adult forms are often marked by speech problems, difficulty swallowing, seizures, and impaired coordination (ataxia). In rare instances, a neonatal form manifests within the first month of life, causing severe intellectual disability and developmental delays, fluid accumulation in the brain (hydrocephalus), and seizures.

A hallmark of Alexander disease is the presence of Rosenthal fibers, which are unusual protein clumps. These fibers are located within astroglial cells, specialized cells that provide support and nourishment to other cells within the brain and spinal cord (the central nervous system).

Inheritance:

Alexander disease typically follows an autosomal dominant inheritance pattern. This means that having just one copy of the mutated gene in each cell is enough to cause the disorder. Most cases arise from new, spontaneous mutations in the gene, occurring in individuals with no family history of the disease. In rare instances, the affected individual inherits the mutated gene from a parent who also has the condition.