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Koolen-de Vries Syndrome
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Koolen-de Vries Syndrome
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Author: Kenneth A. Myers, MD, PhD, FRCPC
Research Institute of the McGill University Medical Centre; Montreal Children’s Hospital, McGill University Health Centre, Montreal, Quebec, Canada 

Reviewed: November 2021

SUMMARY

Koolen-de Vries syndrome (KdVS) is a genetic condition. People with KdVS have a particular set of facial features. People with KdVS also have intellectual disability. People with KdVS may have other medical issues, too. These can include: 

Koolen-de Vries syndrome is caused by mutations in a gene called KANSL1.  

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Disorder Overview

SIGNS AND SYMPTOMS 

Two symptoms appear in all children with KdVS: 

  • Intellectual disability. Intellectual disability is usually mild to moderate.  
  • A particular set of facial features. The same set of facial features are seen in all individuals. They may involve: 
    • Upslanting eyes 
    • Drooping eyelids 
    • A pear-shaped nose 
    • Large, protruding ears 
Mirabel
Mirabel

There are many other possible signs and symptoms.

They include: 

Speech delays

Children with KdVS usually say a first word at 2.5 to 3.5 years of age. They may have a hard time coordinating their mouth to form words. 

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Low muscle tone (floppiness)

Low muscle tone is often seen in those with KdVS. It is especially seen right after birth and during the first 1 or 2 years of life. Children with low tone may develop scoliosis. Scoliosis is an abnormal curvature of the spine.

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Epilepsy

In epilepsy, a child has recurrent seizures. Epilepsy affects about 1 in 3 children with KdVS. The seizures are sometimes long. They may initially be hard to control with antiseizure medications. Children with KdVS can experience different types of seizures. Often, however, the seizures make the child pale and unresponsive. They may also involve sweating, drooling, or vomiting. 

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Brain abnormalities

Children with KdVS often have differences in how their brains are structured. 

Many malformations may occur, but the two most common brain differences in KdVS are: 

  • Problems with the corpus callosum. A structure called the corpus callosum connects the left and right sides of the brain. It can be malformed in those with KdVS.  
  • Enlarged ventricles. Fluid-filled pockets in the brain are called ventricles. They can be enlarged in those with KdVS. 
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Undescended testicles

Testicles fail to descend normally in about half of boys with KdVS. 

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Developmental regressions

This refers to the loss of some developmental milestones already reached. Regressions tend to appear during childhood. They sometimes take place at the same time as seizures. They may occur alongside a specific pattern of brain activity called electrical status epilepticus in sleep (ESES) or continuous spike-wave in sleep (CSWS). The activity is detectable with a test called an electroencephalogram (EEG). Developmental improvement following the regressions is usually slow, and often dependent on how well seizures or epileptiform activity on EEG (ESES/CSWS) can be controlled with medication. 

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Kidney or bladder malformations

These occur in about half of children with KdVS. 

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Heart malformations

These occur in about 1 in 3 children with KdVS. 

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Problems with vision or hearing

Vision and hearing problems are seen in about 2 in 3 children with KdVS. 

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Feeding difficulties

Problems with feeding can occur during infancy. They appear in about 3 in 4 infants with KdVS. 

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CAUSES

KdVS is a genetic condition. It is caused by mutations involving a gene called KANSL1. Healthy people carry two normal copies of the gene. People with KdVS have a problem with one of their KANSL1 genes. 

This can be: 

  • A gene deletion. 95% of people with KdVS have only one copy of the gene. 
  • A coding error. 5% of people with KdVS have a small error in the code of one copy. 

In almost all cases, the mutation that causes KdVS is a new change to the DNA. This is called a de novo genetic change. It was not inherited from either parent. De novo genetic changes occur spontaneously. They are not related to any events during pregnancy. They are not related to other parental factors, including age. 

LAB INVESTIGATIONS

Diagnosis 

To diagnose Koolen-de Vries syndrome: 

  1. A doctor will observe clinical features of KdVS 
  2. The diagnosis will be confirmed through genetic testing 

The genetic testing needed will depend upon what type of genetic change is present. 

Chromosomal microarray

95% of patients are missing a copy of the KANSL1 gene. They will need a chromosomal microarray. This can tell if there are any pieces of DNA that are added or missing. 

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Gene sequencing

5% of patients have a coding error in KANSL1. They will need gene sequencing. This can identify the specific error in the code. In most cases, doctors will order a gene panel for this. The panel will include many genes associated with intellectual disability. KANSL1 will be part of the panel. 

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Further Tests 

Children with KdVS will usually receive a variety of other tests, too. These tests can look for certain problems associated with KdVS. 

Possible tests include: 

Echocardiogram

An echocardiogram can detect abnormalities in the structure of the heart. 

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Magnetic resonance imaging (MRI)

Brain MRI can detect abnormalities in the structure of the brain. 

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X-ray

An X-ray of the spine may be needed. This can detect scoliosis. 

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Ultrasound

An ultrasound can detect abnormalities of the kidneys and bladder. 

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Holoprosencephaly 2

TREATMENT AND THERAPIES

There is not presently any way to treat the genetic cause of KdVS. 

However, there are many ways to treat its symptoms.  

Antiseizure Medication

Seizures are usually treated with these medicines. In many cases, they are only needed for a limited period during childhood. After this period, children can usually slowly wean off the medicine. 

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Speech therapy

Speech therapy can help with speech and language delays.

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Surgery

This may be used for:  

  • Bringing the testicles down into the scrotum when needed 
  • Helping with severe heart, kidney, or bladder abnormalities 
  • Helping with severe scoliosis (a spine problem) 
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Eye treatments

Ophthalmologists are medical eye doctors. They can help address any issues with vision. 

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Physical therapy

A physical therapist can assess and help children with low muscle tone. 

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Braces

A brace may be needed for some cases of scoliosis 

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Hearing treatments

Hearing should be tested. If there are concerns, a referral to an ear, nose, and throat surgeon may be needed. 

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Feeding assistance

Some children will have trouble feeding. They should be checked for their ability to suck and swallow.

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OUTLOOK

Education 

Children with KdVS will usually need extra help in school. They may do better in specialized classes.  

Language delays may be severe in early childhood. However, speech usually improves significantly between the ages of 8 and 12. Support from a speech therapist is very important. The speech therapist can help with language challenges.

Daily Life 

Daily life for children with KdVS can vary from child to child. It depends on what specific issues a child has. Some children will have frequent appointments with different medical specialists and therapists. They may need to take medication daily. Others will need fewer interventions. 

Someone with KdVS will not likely be able to live independently as an adult. This depends on how serious the intellectual disability is. An adult with KdVS may have a hard time: 

  • Finding a job 
  • Taking care of routine, day-to-day tasks, such as buying groceries, cooking meals, and paying bills on time 

Medical Outlook 

There is not yet reliable data on life expectancy in KdVS. However, people with KdVS typically live at least into adulthood. For children with epilepsy, seizures may be hard to control. However, many children grow out of their seizures later in life. They may eventually be able to come off antiseizure medication. 

Koolen de Vries Syndrome

Resources 

Koolen-de Vries Syndrome Foundation 

The mission of the Koolen-de Vries Syndrome Foundation (KDVS Foundation) is to educate, increase awareness, and promote research for the support and enrichment of individuals living with Koolen-de Vries syndrome and their families. 

Childhood Stroke 1

Child Neurology Foundation (CNF) solicits resources from the community to be included on this webpage through an application process. CNF reserves the right to remove entities at any time if information is deemed inappropriate or inconsistent with the mission, vision, and values of CNF. 

Research 

ClinicalTrials.gov for Koolen-de Vries Syndrome are clinical trials that are recruiting or will be recruiting. Updates are made daily, so you are encouraged to check back frequently.  

ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world. This is a resource provided by the U.S. National Library of Medicine (NLM), which is an institute within the National Institutes of Health (NIH). Listing a study does not mean it has been evaluated by the U.S. Federal Government. Please read the NLM disclaimer for details.   

Before participating in a study, you are encouraged to talk to your health care provider and learn about the risks and potential benefits.  

Find Clinical Trials For Koolen-de Vries Syndrome

The information in the CNF Child Neurology Disorder Directory is not intended to provide diagnosis, treatment, or medical advice and should not be considered a substitute for advice from a healthcare professional. Content provided is for informational purposes only.  CNF is not responsible for actions taken based on the information included on this webpage. Please consult with a physician or other healthcare professional regarding any medical or health related diagnosis or treatment options. 

References

Morgan AT, Haaften LV, van Hulst K, Edley C, Mei C, Tan TY, Amor D, Fisher SE, Koolen DA. Early speech development in Koolen de Vries syndrome limited by oral praxis and hypotonia. Eur J Hum Genet. 2018 Jan;26(1):75-84. Epub 2017 Dec 11. PMID: 29225339; PMCID: PMC5839037; https://doi.org/10.1038/s41431-017-0035-9  

Koolen DA, Sharp AJ, Hurst JA, Firth HV, Knight SJ, Goldenberg A, et al. Clinical and molecular delineation of the 17q21.31 microdeletion syndrome. J Med Genet. 2008 Nov;45(11):710-20. Epub 2008 Jul 15. Erratum in: J Med Genet. 2009 Aug;46(8):576. PMID: 18628315; PMCID: PMC3071570; https://doi.org/10.1136/jmg.2008.058701  

Myers KA, Mandelstam SA, Ramantani G, Rushing EJ, de Vries BB, Koolen DA, Scheffer IE. The epileptology of Koolen-de Vries syndrome: Electro-clinico-radiologic findings in 31 patients. Epilepsia. 2017 Jun;58(6):1085-1094. Epub 2017 Apr 25. PMID: 28440867; https://doi.org/10.1111/epi.13746  

Koolen DA, Morgan A, de Vries BBA. Koolen-de Vries Syndrome. 2010 Jan 26 [updated 2019 Jun 13]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2021. PMID: 20301783. 

Koolen-de Vries Syndrome Foundation. Koolen-de Vries Syndrome Foundation 2019 [cited 2021]. Available from: https://KdVSfoundation.org  

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