SNP Shot: Genomic Insights

Periventricular heterotopia (PVH) is a brain development disorder that occurs during fetal development, specifically between the 6th and 24th week of pregnancy. In PVH, neurons, which are nerve cells, fail to migrate correctly to their final locations in the brain. Typically, neurons are formed near the ventricles (fluid-filled cavities) in the center of the brain and then move outwards to create the cerebral cortex, which has a layered structure. However, in PVH, some neurons remain clustered around the ventricles instead of reaching their proper destination. The term "heterotopia" refers to the misplaced neurons.

PVH is often first suspected when seizures begin, commonly during adolescence. The clusters of neurons near the ventricles are then usually identified through MRI scans. While many individuals with PVH have normal intelligence, some may experience mild intellectual disability. Difficulties with reading and spelling (dyslexia), as well as movement problems, have also been observed in some individuals with PVH.

In some cases, individuals with PVH may present with additional features, including more significant brain malformations, a smaller than normal head size (microcephaly), developmental delays, recurring infections, blood vessel abnormalities, digestive issues, or lung problems. PVH can also be associated with other conditions, such as Ehlers-Danlos syndrome, characterized by overly flexible joints, easily stretched skin, and fragile blood vessels.

Inheritance:

The inheritance pattern of PVH varies. When caused by mutations in the FLNA gene, PVH is inherited in an X-linked dominant manner. X-linked conditions are caused by mutated genes located on the X chromosome, one of the sex chromosomes. Dominant inheritance means that only one copy of the altered gene is sufficient to cause the condition. A key feature of X-linked inheritance is that fathers cannot transmit X-linked traits to their sons. In X-linked PVH, affected males typically experience more severe symptoms and often do not survive to birth. Approximately 50% of individuals with X-linked PVH inherit the mutation from their affected mothers. Other cases arise from new mutations in the gene, occurring in individuals with no prior family history of the disorder.

PVH caused by mutations in the ARFGEF2 gene follows an autosomal recessive inheritance pattern. This means that both copies of the gene in each cell must have mutations for the condition to develop. Individuals with PVH and identified ARFGEF2 gene mutations often have a severe form of the disorder, characterized by microcephaly, significant developmental delay, and seizures starting in infancy. In autosomal recessive conditions, parents typically carry one copy of the mutated gene each but do not exhibit any signs or symptoms of the condition.