Koolen-de Vries Syndrome

Koolen-de Vries Syndrome (KdVS) was first identified in 2006 and thus is a relatively “new” syndrome; is a rare genetic condition caused by partial loss of part of chromosome 17 [17q21.31 microdeletion], including the gene called KANSL1. It can also be caused by a change in the KANSL1 gene. These genetic changes can cause developmental delay, learning difficulties, and create possible health concerns. However, 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 23rd pair is 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.

 

Current published literature describing the syndrome is based on small numbers of individuals. Research into the syndrome is continuously on-going and there is great need for parents/caregivers to get involved. Our team of researchers continues to collect and analyze medical data so in the future, they can and will continue developing specific disease management and surveillance strategies. 

What is Koolen de-Vries Syndrome (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 causes 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. It was later estimated at 1 in 55,000 individuals. The prevalence of the microdeletion is now estimated at 1 in 30,000 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.)

How does one inherit KdVS?

Koolen-de Vries Syndrome is an autosomal dominant condition, which means a deletion or mutation of one copy of the KANSL1 gene is enough to cause the disorder. Koolen-de Vries Syndrome is not typically inherited, but occurs randomly during the formation of reproductive cells, or during fetal development.

Most patients with Koolen-de Vries Syndrome are the first in their family to be diagnosed with the disorder. In most cases, the parents of children with Koolen-de Vries Syndrome don’t have the disorder. This means that neither parent has the microdeletion or the missing KANSL1 gene. The mutation or deletion happened randomly during fetal development. The likelihood that they will have another child with Koolen-de Vries Syndrome is very low. If patients with Koolen-de Vries Syndrome have children, there is a 50% chance their child will have the syndrome.

 

 

How do you treat KdVS?

For patients with Koolen-de Vries Syndrome, there are several recommended therapies that most individuals will find beneficial.. The earliest treatment is physiotherapy for feeding problems and motor delay, followed by physical therapy aimed at strengthening the muscles and core strength. As the child grows, the therapy focuses more on developing the child’s fine and gross motor skills with occupational therapy and continued physical therapy. Speech therapy help improve communication skills by using a multitude of techniques which can include sign language, pictures and Alternative and Augmentative Communication (AAC) or speech devices.

Patients should also seek orthopedic, cardiac, renal, and urologic care from physicians if those symptoms manifest. Neurologists can prescribe medication to help reduce epileptic seizures. Educational materials should also be made available for patients families on how to help care for a patient with Koolen-de Vries.

We are a Kool Community

Human Disease Gene Website

Human Disease Genes is a “library of websites for professional information about genes and copy number variants and their clinical consequences”.

The website includes a page dedicated to Koolen-de Vries Syndrome and the KdVS section is maintained and written by Dr. Koolen and Dr. Eichler. The website provides current information on Koolen-de Vries Syndrome including clinical data, molecular data, disease management, and research.

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Unique: Understanding Genes & Chromosomes

“Unique”, a UK based non-profit involved with promoting awareness and publishing education materials about rare chromosome disorders, has published a guide that covers many detailed aspects of Koolen-de Vries Syndrome. We encourage you to learn more about who they are! Information on this page gathered via Unique with permission.

Download disorder guides published by Unique.

Please note that some of the guides translated from English are older versions of the document!

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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.

Features and Genetics

KdVS Features

Features listed below are most likely but keep in mind, every individual is different:

  • Koolen-de Vries Syndrome typically manifests as a developmental delay, and with mild to moderate intellectual disability
  • Most babies and children with this disorder usually have weak muscle tone, and appear floppy (hypotonia)
  • Weak muscle tone causes babies to hold their head up, sit, stand, move, and walk late
  • Babies often have difficulty feeding and may require tube feeding
  • Children often need learning support. Some children do well in mainstream schools, but others require special schooling
  • Children and adults are generally friendly, cheerful, and cooperative
  • About half of those with Koolen-de Vries have recurring seizures (epilepsy)
  • Affected individuals often have distinctive facial features, including a pear-shaped nose, a long face and broad forehead, droopy eyelids, and prominent ears
  • Patients with Koolen-de Vries sometimes have heart defects, kidney problems, and skeletal and bone deformities

If you have any medical concerns for your KdVS individual, please reach out to your medical team. For anyone just starting out on their journey, we offer some treatment examples above and urge you to visit our resources page more more information.

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.

Received a KdVS diagnosis? Click here to view our Resources Page.