SNP Shot: Genomic Insights

Koolen-de Vries syndrome is a genetic condition characterized by delays in development and mild to moderate intellectual disability. Individuals with this syndrome are often described as cheerful, friendly, and cooperative. Hypotonia, or weak muscle tone, is common during childhood. Approximately half of affected individuals experience recurrent seizures, also known as epilepsy.

People with Koolen-de Vries syndrome frequently exhibit distinctive facial features. These can include a high, broad forehead; drooping eyelids (ptosis); narrowed eye openings (blepharophimosis); eyes that slant upwards (upward-slanting palpebral fissures); folds of skin covering the inner corners of the eyes (epicanthal folds); a bulbous nose; and prominent ears. Males with the syndrome may have undescended testicles (cryptorchidism). Some individuals may also have heart defects, such as holes in the walls separating the heart chambers (septal defects), or other cardiac problems, kidney issues, and skeletal abnormalities like foot deformities.

Inheritance:

Koolen-de Vries syndrome is generally considered an autosomal dominant disorder. This means that a deletion or mutation in just one copy of the KANSL1 gene within each cell is enough to cause the condition. In the majority of cases, the syndrome is not inherited but arises spontaneously. The genetic alteration typically occurs as a new, random event either during the formation of egg or sperm cells or in the early stages of fetal development. Consequently, most affected individuals have no family history of the disorder. While theoretically they could pass the condition to their offspring, there are currently no documented cases of individuals with Koolen-de Vries syndrome having children. A significant proportion of individuals with Koolen-de Vries syndrome due to a deletion have a parent carrying a common variation in the 17q21.31 region of chromosome 17, known as the H2 lineage. This H2 lineage, characterized by an inversion of a 900 kb DNA segment, including the region commonly deleted in Koolen-de Vries syndrome, is found in approximately 20% of people with European or Middle Eastern ancestry, but is rare in other populations.

The H2 lineage itself doesn't cause health problems. However, during the transmission of this inverted segment to the next generation, genetic material can sometimes be lost or duplicated. Other contributing factors are also believed to be involved. As a result, despite the relatively common occurrence of the H2 inversion, only a very small fraction of parents with the inversion will have a child with Koolen-de Vries syndrome.