SNP Shot: Genomic Insights

Polymicrogyria is a brain malformation that happens before birth. In a typical brain, the surface has many folds called gyri. However, in individuals with polymicrogyria, there are too many folds, and these folds are abnormally small. The term "polymicrogyria" literally means "many small folds" on the brain's surface.

Polymicrogyria can affect a portion of the brain or the entire brain. If it affects only one side, it's called unilateral. If it affects both sides, it's called bilateral. The symptoms and effects of polymicrogyria vary depending on how much of the brain is affected and which specific areas are involved.

There are different types of polymicrogyria. The mildest form is unilateral focal polymicrogyria, where a small area on one side of the brain is affected. This might cause minor neurological issues like mild seizures that are easily managed with medication. Some individuals with this form may not experience any noticeable problems.

Bilateral forms of polymicrogyria tend to cause more significant neurological problems. Symptoms can include recurring seizures (epilepsy), developmental delays, misaligned eyes, difficulties with speech and swallowing, and muscle weakness or paralysis. The most severe type, bilateral generalized polymicrogyria, affects the entire brain. This results in severe intellectual disability, movement problems, and seizures that are hard or impossible to control with medication.

Polymicrogyria often occurs as an isolated condition, but it can also occur alongside other brain abnormalities. It can also be a feature of various genetic syndromes characterized by intellectual disability and multiple birth defects, such as 22q11.2 deletion syndrome, Adams-Oliver syndrome, Aicardi syndrome, Galloway-Mowat syndrome, Joubert syndrome, and Zellweger spectrum disorder.

Inheritance:

Isolated polymicrogyria can be inherited in different ways. Some forms, like bilateral frontoparietal polymicrogyria (linked to ADGRG1 gene mutations), follow an autosomal recessive inheritance pattern. This means that both copies of the responsible gene in each cell must have mutations for the condition to develop. Parents of individuals with autosomal recessive conditions typically carry one copy of the mutated gene but don't show symptoms themselves. Polymicrogyria can also be inherited in an autosomal dominant manner, where only one copy of the altered gene in each cell is enough to cause the disorder. Other forms appear to have an X-linked inheritance pattern. Genes involved in X-linked conditions are located on the X chromosome (a sex chromosome). A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Some individuals with polymicrogyria have family members with the condition, while others have no family history. When someone is the only affected individual in their family, determining the cause and potential inheritance pattern can be challenging.