Koolen de Vries syndrome

Información en español Title

Other Names:

17q21.31 deletion syndrome; Monosomy 17q21.31; Microdeletion 17q21.31 syndrome; 17q21.31 deletion syndrome; Monosomy 17q21.31; Microdeletion 17q21.31 syndrome; Chromosome 17q21.31 microdeletion syndrome; 17q21.31 microdeletion syndrome; KANSL1-Related Intellectual Disability Syndrome See More

Categories:

Chromosome Disorders; Congenital and Genetic Diseases

Summary Summary

Koolen de Vries syndrome is a disorder characterized by developmental delay, mild to moderate intellectual disability, congenital malformations, and behavioral features.^[1]^[2] Developmental delay is noted from an early age. Other problems include weak muscle tone (hypotonia) in childhood, recurrent seizures (epilepsy), and distinctive facial features. Males with Koolen de Vries syndrome often have undescended testes (cryptorchidism). Other symptoms may include defects in the walls between the chambers of the heart (septal defects) or other heart defects, kidney problems, and skeletal anomalies such as foot deformities.^[1] It is caused by mutations in the KANSL1 gene, or by the loss of a small amount of genetic material in chromosome 17 that includes the KANSL1 gene (chromosome 17 q21.31 microdeletion).^[2]^[3] Inheritance is autosomal dominant. Treatment may include physiotherapy, speech therapy, and educational programs, as well as medication for epilepsy and surgical treatment for malformations needing to be corrected.^[2]

Last updated: 3/3/2017

Symptoms Symptoms

The most frequent symptoms (present in more than 75% of the cases) may include:^[2]^[1]

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)
Developmental delay/ intellectual disability
Low muscle tone (hypotonia) in childhood
Friendly and cheerful attitude

In about 50% to 75% of the cases the following symptoms may be present:^[2]

Epilepsy
Skin and hair problems
Nasal speech
Narrow/high palate
Dental anomalies
Slender/long fingers
Joints that are too flexible (hypermobility) and/or joint dislocation or deformation
Brain anomalies
Kidney and genital anomalies

Less frequent symptoms (25%-50%) are:^[2]

Far-sightedness (hypermetropia)
Crossed eyes (strabismus)
Narrow hands
Small hands
Heart defects
Hip dislocation/dysplasia
Persistence of fingertip pads
Slender lower limbs
Positional deformity of the feet
Abnormal curvature of the spine (scoliosis/kyphosis)

In some cases (10% to 25% of the cases) the following symptoms may be present:^[2]

Hearing loss due to chronic infection of the ears (otitis media)
Low birth weight
Short stature
Abnormal head shape
Sunken chest (pectus excavatum)

Uncommon symptoms (in less than 10% of the cases) include:^[2]

Cleft lip/palate
Very small head (microcephaly)
Clouding of the lens in the eye (cataract)
Narrowing of the muscular opening at the lower end of the stomach that connects to the intestines (pyloric stenosis)
Vertebras that are joined together (fused vertebrae)
A condition in which a bone (vertebra) in the spine moves forward out of the proper position onto the bone below it (spondylolisthesis)
Hypothyroidism

Last updated: 3/3/2017

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Blepharophimosis	Very frequent (present in 80%-99% of cases)
Broad forehead	Very frequent (present in 80%-99% of cases)
Bulbous nose	Very frequent (present in 80%-99% of cases)
Coarse facial features	Very frequent (present in 80%-99% of cases)
Epicanthus	Very frequent (present in 80%-99% of cases)
Everted lower lip vermilion	Very frequent (present in 80%-99% of cases)
Generalized hypotonia	Very frequent (present in 80%-99% of cases)
High forehead	Very frequent (present in 80%-99% of cases)
Intellectual disability	Very frequent (present in 80%-99% of cases)
Long face	Very frequent (present in 80%-99% of cases)
Muscular hypotonia	Very frequent (present in 80%-99% of cases)
Overfolded helix	Very frequent (present in 80%-99% of cases)
Overfriendliness	Very frequent (present in 80%-99% of cases)
Prominent nasal bridge	Very frequent (present in 80%-99% of cases)
Protruding ear	Very frequent (present in 80%-99% of cases)
Ptosis	Very frequent (present in 80%-99% of cases)
Thick nasal alae	Very frequent (present in 80%-99% of cases)
Underdeveloped nasal alae	Very frequent (present in 80%-99% of cases)
Upslanted palpebral fissure	Very frequent (present in 80%-99% of cases)
Wide nasal bridge	Very frequent (present in 80%-99% of cases)
Abnormality of hair pigmentation	Frequent (present in 30%-79% of cases)
Abnormality of hair texture	Frequent (present in 30%-79% of cases)
Abnormality of the cardiac septa	Frequent (present in 30%-79% of cases)
Abnormality of the dentition	Frequent (present in 30%-79% of cases)
Aplasia/Hypoplasia of the corpus callosum	Frequent (present in 30%-79% of cases)
Arachnodactyly	Frequent (present in 30%-79% of cases)
Conspicuously happy disposition	Frequent (present in 30%-79% of cases)
Cryptorchidism	Frequent (present in 30%-79% of cases)
Delayed speech and language development	Frequent (present in 30%-79% of cases)
Feeding difficulties in infancy	Frequent (present in 30%-79% of cases)
High palate	Frequent (present in 30%-79% of cases)
High, narrow palate	Frequent (present in 30%-79% of cases)
High-grade hypermetropia	Frequent (present in 30%-79% of cases)
Hip dislocation	Frequent (present in 30%-79% of cases)
Hip dysplasia	Frequent (present in 30%-79% of cases)
Hypermetropia	Frequent (present in 30%-79% of cases)
Hypopigmentation of hair	Frequent (present in 30%-79% of cases)
Hypospadias	Frequent (present in 30%-79% of cases)
Hypotrophy of the small hand muscles	Frequent (present in 30%-79% of cases)
Joint hyperflexibility	Frequent (present in 30%-79% of cases)
Joint hypermobility	Frequent (present in 30%-79% of cases)
Kyphosis	Frequent (present in 30%-79% of cases)
Macrotia	Frequent (present in 30%-79% of cases)
Microdontia	Frequent (present in 30%-79% of cases)
Narrow palate	Frequent (present in 30%-79% of cases)
Narrow palm	Frequent (present in 30%-79% of cases)
Nasal speech	Frequent (present in 30%-79% of cases)
Pear-shaped nose	Frequent (present in 30%-79% of cases)
Poor speech	Frequent (present in 30%-79% of cases)
Positional foot deformity	Frequent (present in 30%-79% of cases)
Prominent fingertip pads	Frequent (present in 30%-79% of cases)
Scoliosis	Frequent (present in 30%-79% of cases)
Seizures	Frequent (present in 30%-79% of cases)
Slender finger	Frequent (present in 30%-79% of cases)
Strabismus	Frequent (present in 30%-79% of cases)
Ventriculomegaly	Frequent (present in 30%-79% of cases)
Abnormality of dental enamel	Occasional (present in 5%-29% of cases)
Aortic dilatation	Occasional (present in 5%-29% of cases)
Bicuspid aortic valve	Occasional (present in 5%-29% of cases)
Cataract	Occasional (present in 5%-29% of cases)
Dry skin	Occasional (present in 5%-29% of cases)
Hydronephrosis	Occasional (present in 5%-29% of cases)
Hypodontia	Occasional (present in 5%-29% of cases)
Hypotelorism	Occasional (present in 5%-29% of cases)
Hypothyroidism	Occasional (present in 5%-29% of cases)
Ichthyosis	Occasional (present in 5%-29% of cases)
Microcephaly	Occasional (present in 5%-29% of cases)
Pectus excavatum	Occasional (present in 5%-29% of cases)
Prominent metopic ridge	Occasional (present in 5%-29% of cases)
Pyloric stenosis	Occasional (present in 5%-29% of cases)
Renal duplication	Occasional (present in 5%-29% of cases)
Small for gestational age	Occasional (present in 5%-29% of cases)
Spondylolisthesis	Occasional (present in 5%-29% of cases)
Ureteral duplication	Occasional (present in 5%-29% of cases)
Vertebral fusion	Occasional (present in 5%-29% of cases)
Vesicoureteral reflux	Occasional (present in 5%-29% of cases)
Abnormality of cardiovascular system morphology	Very rare (present in 1%-4% of cases)
Abnormality of the urinary system	Very rare (present in 1%-4% of cases)
Broad chin	Very rare (present in 1%-4% of cases)
Anteverted ears	-
Atrial septal defect	-
Autosomal dominant inheritance	-
Cleft upper lip	-
Contiguous gene syndrome	-
Eczema	-
Failure to thrive	-
Intrauterine growth retardation	-
Open mouth	-
Pulmonic stenosis	-
Sacral dimple	-
Sporadic	-
Variable expressivity	-
Ventricular septal defect	-
Wide intermamillary distance	-
Widely spaced teeth	-

Last updated: 9/1/2017

Cause Cause

Koolen de Vries syndrome is caused by either:

Mutations in the KANSL1 gene, resulting in the loss of function of this gene.
Loss (deletions) of a small amount of genetic material (microdeletion) from chromosome 17, that includes the KANSL1 gene.

Most of the cases are due to the microdeletion. The microdeletion occurs on the long (q) arm of chromosome 17 at a location q21.31. While the exact size of the deletion varies among individuals, most are missing several genes. However, because people with KANSL1 gene mutations have the same signs and symptoms as those with the microdeletion, researchers have concluded that the loss of this gene accounts for the features of this disorder.^[1]

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 involved in controlling the activity of other genes, and in the development and function of many parts of the body.^[1] The relationship of KANSL1 gene loss to the specific signs and symptoms of Koolen de Vries syndrome is unclear.^[1]^[2]

Last updated: 3/6/2017

Inheritance Inheritance

Most people with Koolen de Vries syndrome (KdVS) are the first person born in their family with the syndrome. So in almost every case, the parents of a child with KdVS do not have KdVS and therefore do not have a changed (mutated) or missing (deleted) copy of the KANSL1 gene.^[1]^[2]^[4] This is because the mutation or deletion happened by a chance mistake when the sperm or egg was being made. The chance this same mistake will happen again is low. So if a person without KdVS has a child with KdVS, the risk of having other children with the KdVS is low (probably less than 1 in 100).^[2]

If a person with KdVS has a child, then there is a 50% chance their child will have KdVS. This means that there is also an equal chance (also 50%) of having a child who does not have KdVS.^[1]^[2] In genetic terms, KdVS is called an autosomal dominant syndrome to describe the way it is inherited.

Last updated: 3/3/2017

Diagnosis Diagnosis

17q21.31 microdeletion syndrome is diagnosed in individuals who have a deletion of 500,000 to 650,000 DNA building blocks (base pairs) at chromosome 17q21.31. The diagnosis can be made by various genetic testing methods, including FISH and array CGH. This condition cannot be diagnosed by traditional chromosome tests (karyotype) that look at chromosome banding patterns under the microscope because the deletion is too small to be detected.^[5]

Last updated: 5/4/2010

The symptoms are very variable. Besides developmental delay and intellectual disability, no single clinical feature is required to establish the diagnosis, although childhood low muscle tone (hypotonia) is a common feature, reported in almost all affected people.

To establish the diagnosis of the syndrome one of the following is needed:^[2]

A 17q21.31 microdeletion involving at least KANSL1
A mutation in the KANSL1 gene (through an exam known as sequence analysis)

Last updated: 3/3/2017

Testing Resources

Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment Treatment

Treatment depends on the symptoms and may include:^[2]

Early intervention with physiotherapy for feeding problems and motor delay
Physical therapy aimed at strengthening the muscles
Therapy to improve development of the child's fine and gross motor skills
Speech therapy, sign language, pictures and computer touch screens aiming to improve communication skills
Educational programming directed to the specific disabilities identified
Routine antiepileptic drugs
Orthopedic care for scoliosis, hip dislocation, and positional deformities of the feet
Standard treatment for cardiac, renal, urologic, and other medical issues
Surgery cryptorchidism if indicated.

Affected people should have routine examinations by a primary care physician and pediatrician, cardiologist, nephrologist, and/or urologist. Referrals to other specialists is indicated if neurological or other problems are suspected.^[2]^[6]

Last updated: 3/3/2017

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

The 17q21.31 Research Project aims to better characterize the clinical spectrum of Koolen de Vries syndrome, to provide insights into the molecular effects of the 17q21.31 deletion and KANSL1 mutation, and to explore possibilities for treatment. These research studies are being conducted by investigators at the Department of Human Genetics, Radbound Univeristy Medical Center, Nijmegen, Netherlands and at the Department of Genome Sciences, University of Washington, Seattle, United States.
Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Chromosome Disorder Outreach
PO Box 724
Boca Raton, FL 33429
Telephone: 561-395-4252
E-mail: info@chromodisorder.org
Website: http://www.chromodisorder.org
Supporting Families with Koolen-de Vries Syndrome
PO Box 946
Brownsburg, IN 46112
Telephone: 317-514-5534
E-mail: http://www.koolenfamily.com/?page_id=5#contact-wrapper
Website: http://www.supportingkdvs.com/
Unique – Rare Chromosome Disorder Support Group
G1, The Stables
Station Road West
Surrey
RH8 9EE
United Kingdom
Telephone: +44 (0)1883 723356
E-mail: info@rarechromo.org
Website: http://www.rarechromo.org

Social Networking Websites

Visit the Koolen de Vries Europe group on Facebook.

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Koolen de Vries syndrome. This website is maintained by the National Library of Medicine.
Unique is a source of information and support to families and individuals affected by rare chromosome disorders. Click on the link to view information about 17q21.31 microdeletion syndrome.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Koolen de Vries syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

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August 31, 2017
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August 10, 2017

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My genetic counselor said my husband and I don’t have the deletion that caused our son’s Koolen de Vries syndrome (KdVS), but that we are at a slightly increased risk of having another child with KdVS. Can you help me understand why? See answer
My daughter has been diagnosed with 17q21.31 microdeletion syndrome, and I would like more information on this condition. See answer

Have a question? Contact a GARD Information Specialist.

References References

Koolen-de Vries syndrome. Genetics Home Reference. 2013; http://ghr.nlm.nih.gov/condition=17q2131microdeletionsyndrome.
Koolen DA & de Vries BBA. KANSL1-Related Intellectual Disability Syndrome. GeneReviews. 2013; https://www.ncbi.nlm.nih.gov/books/NBK24676/.
Koolen DA & cols. Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome. Nat Genet. 2012; 44::639–41.
Bernardo P, Madia F, Santulli L, Del Gaudio L, Caccavale C, Zara F, Traverso M, Cirillo M, Striano S, Coppola A. 17q21.31 microdeletion syndrome: Description of a case further contributing to the delineation of Koolen-de Vries syndrome. Brain Dev. 2016 Aug; 38(7):663-8. https://www.ncbi.nlm.nih.gov/pubmed/26897099.
Koolen DA, de Vries BBA. 17q21.31 Microdeletion Syndrome. GeneReviews. January 26, 2010; http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=mdel17q21_31. Accessed 5/4/2010.
Koolen-De Vries syndrome. Orphanet. January, 2009; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96169.