What is KDVS?

Koolen-de Vries Syndrome is genetic syndrome involving the 17th chromosome and is caused by a microdeletion at 17q21.31 (including the KANSL1 gene) or is caused by a change or mutation of the KANSL1 gene. The microdeletion or the KANSL1 mutation cause developmental delays, learning difficulties and can cause a number of other health concerns.

In 2008, the prevalence of Koolen-de Vries Syndrome was estimated at 1 in 16,000 individuals. The prevalence of the microdeletion is now estimated at 1 in 55,000 individuals Due to the limited number of identified KANSL1 mutations, at this time the prevalence of the KANSL1 mutation can not be determined. Mutations of KANSL1 may be as frequent as the microdeletion, but more studies are required to determine the prevalence. (Koolen et al. 2016. The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant. Eur J Hum Genet 24(5): 652-659.)

Unique, a non-profit involved with awareness and information about rare chromosome disorders, has published a guide that covers many detailed aspects of Koolen-de Vries Syndrome. We encourage you to visit their website and download the guide.

Has someone in your family received a diagnosis of KdVS and are unsure of what to do next?
Please click here to find a list of helpful resources, including a quick “What to do after receiving a diagnosis” guide.

From Unique’s Guide:

Koolen-De Vries Syndrome

Koolen-De Vries syndrome (you pronounce Vries as “freeze”) is a rare genetic condition caused by the loss of part of chromosome 17 [17q21.31 microdeletion] including the gene called KANSL1, or by a change in the KANSL1 gene. These genetic changes cause developmental delay, learning difficulties and possibly some health concerns as well. But individuals vary, both in the degree to which they are affected and in other effects.

The KANSL1 gene is found on the long arm of chromosome 17. Chromosomes are the structures in the nucleus of the body’s cells that carry genetic information, telling the body how to develop and function. They come in pairs, one from each parent, and are numbered 1 to 22 approximately from largest to smallest. The 23 pair are the sex chromosomes. XX for females and XY for males. Each chromosome has a short [p] arm and a long [q] arm. KANSL1 is found at a place on the long arm of chromosome 17 called 17q21.31. Until 2012 Koolen-De Vries syndrome was called 17q21.31 microdeletion syndrome.

Most likely features of Koolen-De Vries Syndrome

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  • Young babies are floppy
  • Young babies have difficulty feeding. They may need tube feeding for a time
  • Babies hold their head up, sit, stand, move and walk late
  • Children start speaking late and have difficulty making all the sounds of speech
  • Children need support with learning. Some children are taught in mainstream schools, others do better in a special school
  • Children and adults are generally friendly and cooperative
  • Children and adults have recognizable facial features, especially a pear-shaped nose with a bulbous tip and a long face. The typical facial features may not be seen in babies and young children.

Chromosome 17q and genetic testing

You can’t see chromosomes with the naked eye, but if you stain them and magnify them under a microscope, you can see that each one has a distinctive pattern of light and dark bands. Each band contains millions of base pairs of DNA. Base pairs are the chemicals in DNA that form the ends of the “rungs” of its ladder-like structure and make up genes.

A technique known as microarray comparative genomic hybridization [array CGH] can show the loss of tiny amounts of DNA from a chromosome or a change in a particular gene. Using this technique, laboratory geneticists can see whether the 17q21.31 region including the KANSL1 gene is missing. Another technique known as FISH can also be used to show that DNA is missing, but these techniques do not show tiny changes in the KANSL1 gene. A technique known as DNA sequence analysis is used to identify small changes in KANSL1 at the base pair level.

The KANSL1 gene is found between base pair 44,107,282-44,302,733 on chromosome 17. These numbers are from Human Genome build 19. The human genome is updated as more information is found; each new version is called a “build”. In each build, the base pair numbers may change slightly. In February 2013, hg19 is the newest build. Confusingly, hg19 is also sometimes called Genome Reference Consortium human genome 37, GRCh37. In the previous build hg18, KANSL1 was found between base pairs 41,463,129-41,658,510.

Sources
The information in the Unique guide is drawn from information on the 17q21 website; from articles in the medical literature; and from Unique’s database [Varela 2006; El-Chehadeh-Djebbar 2011; Write 2011; Terrone 2012; Unique]. With the first-named author and publication date you can look for abstracts or original articles on the internet in PubMed (www.ncbi.nlm.nih.gov/pubmed). When this updated guide was compiled, Unique had 51 members with Koolen-De Vries syndrome. This information is used on the Supporting Families with KdVS Website with permission from Unique.