Koolen-de Vries syndrome

Koolen-de Vries syndrome is a rare genetic disorder whose central features are delayed development and mild to moderate intellectual disability. Children usually have low muscle tone, and about half develop recurrent seizures. Many share a recognizable set of facial features, including a high broad forehead, droopy eyelids, narrow eye openings, upward-slanting eyes, a bulbous nose and prominent ears, and the people affected are often described as cheerful, sociable and cooperative. Boys frequently have undescended testes, and some individuals have heart defects, kidney problems or foot deformities. The cause is the loss of one working copy of the KANSL1 gene, usually through a small deletion on the long arm of chromosome 17 at position q21.31 and occasionally through a mutation inside the gene. It follows an autosomal dominant pattern but almost always arises as a new event, and the prevalence is estimated at about 1 in 16,000, likely an undercount because the genetic cause is often not tested for.