Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


Koolen-de Vries syndrome ...; Deletion 17q21.31 (Koolen-de Vries syndrome) - Gen KANSL1 and chromosome 17


Syndrome Koolen-de Vries, also known as deletion or microdeletion syndrome 17q21.31, is a process characterized by developmental delay and mild to moderate mental retardation. Usually, people affected manifest an attitude described as cheerful, sociable and cooperative. These individuals manifest hypotonia in childhood and about half have recurrent episodes of epilepsy. People usually have distinctive facial features, including a high and broad forehead; ptosis; blepharophimosis; palpebral fissures inclined upwards; epicanto; a round nose; and prominent ears. Often, men with Koolen-de Vries syndrome have cryptorchidism. In addition, some affected individuals have septal defects or other heart abnormalities, kidney problems and skeletal abnormalities such as foot deformities.

Syndrome Koolen-de Vries is due to genetic changes that eliminate the function of a copy of KANSL1 (NSL KAT8 complex regulatory subunit 1) gene in every cell. This gene, located on the long arm of chromosome 17 (17q21.31), encodes a subunit of NSL KAT8 regulator. This complex is classified as a histone acetyltransferase complex (HAT). It helps regulate gene activity through modification of chromatin, the DNA complex protein and joining DNA in chromosomes. The protein encoded from KANSL1 gene found in most organs and tissues before birth and throughout life. For their participation in controlling the activity of other genes, it plays an important role in the development and function of many parts of the body.

Most affected individuals have a microdeletion of genetic material, including KANSL1 gene from one copy of chromosome 17. A small number of people with Koolen-de Vries syndrome have a microdeletion on chromosome 17, but have a mutation in the KANSL1 gene that makes a copy of the gene is not functional. The microdeletion responsible of Koolen-de Vries syndrome occurs in the long arm of chromosome 17 in the region q21.31. While the exact size of the deletion varies among affected individuals, most have a deletion of 500 kb containing several genes. However, because individuals with gene mutations KANSL1 have the same signs and symptoms than those who have the microdeletion, it has concluded that the loss of this gene is responsible for the characteristics of this entity. The loss of a copy of KANSL1 gene in every cell alters the development and function of various organs and tissues, although the relationship between the loss of KANSL1 genes and specific signs and symptoms of Koolen-de Vries syndrome is unclear .

Syndrome Koolen-de Vries is inherited as an autosomal dominant pattern because a deletion or mutation affecting a copy of the gene in every cell KANSL1 is sufficient to express syndrome; however, in most cases are not inherited. The genetic change occurs more frequently as a random event during the formation of reproductive cells or early embryonic development, so affected individuals often have no history of the disease in his family. While it is possible that they can transmit the disease to their children, they have not been reports of individuals with Koolen-de Vries who have had offspring syndrome.

Most people with Koolen-de Vries syndrome due to a deletion have at least one parent with a common variant of the 17q21.31 region of chromosome 17 called the lineage H2. This variant has been identified in 20% of people of European descent and the Middle East, although it is rare in other populations. In the line H2, a segment of 900 kb of DNA, including the region deleted in most cases of Koolen-de Vries syndrome, has been the subject of an investment. An investment involves two breaks in a chromosome; the unit resulting DNA is inverted and reinserted into the chromosome. People with H2 lineage have no health problems related to investment. However, the genetic material can be lost or duplicated when the investment is transmitted to the next generation. It is believed that other unknown factors may play a role in this process. So while investment is very common, only a very small percentage of parents with investing have a child affected by the syndrome of Koolen-de Vries.

Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome Koolen-de Vries, by complete PCR amplification of exons KANSL1 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).