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What is Koolen-de Vries Syndrome (KdVS)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional.
KdVS was discovered in 2006 by Dr. David Koolen and Dr. Burt De Vries. It is a disorder characterized by developmental delay and mild to moderate intellectual disability. People with this disorder typically have a disposition that is described as cheerful, sociable, and cooperative. They usually have weak muscle tone (Hypotonia ) in childhood. About half have recurrent seizures (epilepsy). There are about 135 Kool Kids currently diagnosed in the US. It is estimated that there are about 500 Kool Kids worldwide.
Affected individuals often have distinctive facial features including a high, broad forehead; droopy eyelids (ptosis); a narrowing of the eye openings (blepharophimosis); outer corners of the eyes that point upward (upward-slanting palpebral fissures); skin folds covering the inner corner of the eyes (epicanthal folds); a bulbous nose; and prominent ears. Males with Koolen-de Vries syndrome often have undescended testes (cryptorchidism). Defects in the walls between the chambers of the heart (septal defects) or other cardiac abnormalities, kidney problems, and skeletal anomalies such as foot deformities occur in some affected individuals.
Humans normally have 46 chromosomes in each cell, divided into 23 pairs. Two copies of chromosome 17, one copy inherited from each parent, form one of the pairs. Chromosome 17 spans about 81 million DNA building blocks (base pairs) and represents between 2.5 and 3 percent of the total DNA in cells.
Identifying genes on each chromosome is an active area of genetic research. Because researchers use different approaches to predict the number of genes on each chromosome, the estimated number of genes varies. Chromosome 17 likely contains 1,200 to 1,300 genes that provide instructions for making proteins. These proteins perform a variety of different roles in the body.
Genes on chromosome 17 are among the estimated 20,000 to 25,000 total genes in the human genome. Chromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 83 million base pairs (the building material of DNA) and represents between 2.5 and 3% of the total DNA in cells.
Identifying genes on each chromosome is an active area of genetic research. Because researchers use different approaches to predict the number of genes on each chromosome, the estimated number of genes varies. Chromosome 17 likely contains between 1,200 and 1,500 genes. It also contains the Homeobox B gene cluster.
At the Department of Human Genetics, Radboud University Medical Center, they have developed a clinical survey, allowing parents to submit clinical data in a systematic way. This will allow the development of specific management protocols.
What are the genetic changes related
to Koolen-de Vries syndrome?
Koolen-de Vries syndrome is caused by genetic changes that eliminate the function of one copy of the KANSL1 gene in each cell. Most affected individuals are missing a small amount of genetic material, including the KANSL1 gene, from one copy of chromosome 17. This type of genetic abnormality is called a micro-deletion. A small number of individuals with Koolen-de Vries syndrome do not have a chromosome 17 micro deletion but instead have a mutation within the KANSL1 gene that causes one copy of the gene to be nonfunctional.
The micro-deletion that causes Koolen-de Vries syndrome occurs on the long (q) arm of chromosome 17 at a location designated q21.31. While the exact size of the deletion varies among affected individuals, most are missing a sequence of about 500,000 DNA building blocks (base pairs) containing several genes. However, because individuals with KANSL1 gene mutations have the same signs and symptoms as those with the micro deletion, researchers have concluded that the loss of this gene accounts for the features of this disorder.
The KANSL1 gene provides instructions for making a protein that helps regulate gene activity (expression) by modifying chromatin. Chromatin is the complex of DNA and protein that packages DNA into chromosomes. The protein produced from the KANSL1 gene is found in most organs and tissues of the body before birth and throughout life. By its involvement in controlling the activity of other genes, this protein plays an important role in the development and function of many parts of the body. Loss of one copy of this gene impairs normal development and function, but the relationship of KANSL1 gene loss to the specific signs and symptoms of Koolen-de Vries syndrome is unclear.
Read more about the KANSL1 gene and chromosome 17.
Dr. David Koolen (Right) and Dr. Bert De Vries (Left).
Can KdVS be inherited?
Koolen-de Vries syndrome is considered an autosomal dominant condition because a deletion or mutation affecting one copy of the KANSL1 gene in each cell is sufficient to cause the disorder. In most cases, the disorder is not inherited. The genetic change occurs most often as a random event during the formation of reproductive cells (eggs and sperm) or in early fetal development. Affected people typically have no history of the disorder in their family. While it is possible for them to pass the condition on to their children, no individuals with Koolen-de Vries syndrome have been known to reproduce.
Most people with Koolen-de Vries syndrome caused by a deletion have had at least one parent with a common variant of the 17q21.31 region of chromosome 17 called the H2 lineage. This variant is found in 20 percent of people of European and Middle Eastern descent, although it is rare in other populations. In the H2 lineage, a 900 kb segment of DNA, which includes the region deleted in most cases of Koolen-de Vries syndrome, has undergone an inversion. An inversion involves two breaks in a chromosome; the resulting piece of DNA is reversed and reinserted into the chromosome.
People with the H2 lineage have no health problems related to the inversion. However, genetic material can be lost or duplicated when the inversion is passed to the next generation. Other, unknown factors are thought to play a role in this process. So while the inversion is very common, only an extremely small percentage of parents with the inversion have a child affected by Koolen-de Vries syndrome.
Dr. Koolen's Clinical Survey
Each year, a larger number of people are diagnosed with Koolen-de Vries Syndrome as the genetic tests become more accessible and more commonplace.
Dr. Koolen continues to gather data on individuals with KDVS. Parents and caregivers of children/adults with KDVS are kindly asked to share information to help Dr. Koolen continue to research, refine and define Koolen-de Vries Syndrome.
Dr. Koolen has developed a clinical survey which will allow data to be collected in a systematic manner to allow proper scientific analysis. Questions on the survey focus mostly on the health and development of the individual with KDVS.
The survey can be found at :http://www.17q21.com/en/Clinical%20survey.php.
FAQ's INFORMATION GATHERED FROM
The United States National Library of Medicine, operated by the United States federal government, is the world's largest medical library. Located in Bethesda, Maryland, the NLM is an institute within the National Institutes of Health.
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional.
