SNP Shot: Genomic Insights

Dandy-Walker malformation is a condition that disrupts brain development, especially the cerebellum, which controls movement. The cerebellum develops abnormally in individuals with this condition, leading to observable malformations through medical imaging. Specifically, the vermis (the central part of the cerebellum) might be missing, unusually small, or misplaced. Also, the right and left cerebellar hemispheres might be underdeveloped. Furthermore, the fourth ventricle (a fluid-filled space between the brainstem and cerebellum) and the posterior fossa (the skull area housing the cerebellum and brainstem) are often abnormally enlarged. These brain differences can lead to difficulties with movement, coordination, thinking, mood, and other neurological functions.

In most cases of Dandy-Walker malformation, symptoms appear either at birth or within the first year of life due to the abnormal brain development. Some infants develop hydrocephalus (fluid buildup in the brain), potentially causing macrocephaly (an enlarged head). Intellectual disability, ranging from mild to severe, affects up to half of those with the condition, while others with normal intelligence may experience learning challenges. Delayed development is common, particularly in motor skills such as crawling, walking, and coordination. Muscle stiffness, spastic paraplegia (partial paralysis of the lower limbs), and seizures can also occur. Hearing and vision issues, although rare, can also be present.

Less frequently, individuals with Dandy-Walker malformation may have other brain abnormalities. These can include agenesis of the corpus callosum (underdevelopment or absence of the tissue connecting the brain's hemispheres), occipital encephalocele (a sac-like protrusion of the brain through the back of the skull), or the failure of neurons to migrate correctly during brain development. These additional malformations often lead to more severe symptoms.

While Dandy-Walker malformation mainly affects the brain, other systems can be involved. These include heart defects, urogenital tract malformations, polydactyly (extra fingers or toes), syndactyly (fused fingers or toes), or abnormal facial features.

In a smaller percentage (10-20%) of individuals, the symptoms of Dandy-Walker malformation don't surface until later childhood or even adulthood. These individuals often exhibit a different set of features compared to those affected in infancy. These features may include headaches, an unsteady gait, facial palsy (paralysis of facial muscles), increased muscle tone, muscle spasms, and alterations in mental state and behavior. In rare instances, people with Dandy-Walker malformation experience no health issues associated with the condition.

The most common cause of death in people with Dandy-Walker malformation is related to hydrocephalus or complications arising from its treatment.

Inheritance:

Most Dandy-Walker malformation cases are sporadic, meaning they occur in individuals without a family history of the disorder. However, a small number of cases appear to run in families, although a clear inheritance pattern is lacking. The risk of developing the condition is likely influenced by a combination of genetic and environmental factors. First-degree relatives (like siblings and children) of individuals with Dandy-Walker malformation have a higher risk compared to the general population. When Dandy-Walker malformation is part of a larger genetic condition, it is inherited according to the inheritance pattern of that specific genetic condition.