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

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 104 |

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Blepharophimosis	Narrow opening between the eyelids	0000581
Broad forehead	Increased width of the forehead Wide forehead [ more ]	0000337
Bulbous nose		0000414
Coarse facial features	Coarse facial appearance	0000280
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
Everted lower lip vermilion	Outward turned lower lip Drooping lower lip [ more ]	0000232
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Global developmental delay		0001263
High forehead		0000348
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Long face	Elongation of face Increased length of face Increased height of face Vertical overgrowth of face Vertical enlargement of face Vertical elongation of face [ more ]	0000276
Muscular hypotonia	Low or weak muscle tone	0001252
Overfolded helix	Overfolded ears	0000396
Overfriendliness		0100025
Prominent nasal bridge	Elevated nasal bridge High nasal bridge Prominent bridge of nose Prominent nasal root Protruding bridge of nose Protruding nasal bridge [ more ]	0000426
Protruding ear	Prominent ear Prominent ears [ more ]	0000411
Ptosis	Drooping upper eyelid	0000508
Thick nasal alae		0009928
Underdeveloped nasal alae	Underdeveloped tissue around nostril	0000430
Upslanted palpebral fissure	Upward slanting of the opening between the eyelids	0000582
Wide nasal bridge	Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal bridge [ more ]	0000431
30%-79% of people have these symptoms
Abnormal cardiac septum morphology		0001671
Abnormality of hair pigmentation	Abnormality of hair color	0009887
Abnormality of hair texture		0010719
Abnormality of the dentition	Abnormal dentition Abnormal teeth Dental abnormality [ more ]	0000164
Aplasia/Hypoplasia of the corpus callosum		0007370
Arachnodactyly	Long slender fingers Spider fingers [ more ]	0001166
Conspicuously happy disposition		0100024
Cryptorchidism	Undescended testis Undescended testes [ more ]	0000028
Delayed speech and language development	Deficiency of speech development Delayed language development Delayed speech Delayed speech acquisition Delayed speech development Impaired speech and language development Impaired speech development Language delay Language delayed Language development deficit Late-onset speech development Poor language development Speech and language delay Speech and language difficulties Speech delay [ more ]	0000750
Feeding difficulties in infancy		0008872
High hypermetropia	Severe farsightedness Severe long-sightedness [ more ]	0008499
High palate	Elevated palate Increased palatal height [ more ]	0000218
High, narrow palate	Narrow, highly arched roof of mouth Narrow, high-arched roof of mouth [ more ]	0002705
Hip dislocation	Dislocated hips Dislocation of hip [ more ]	0002827
Hip dysplasia		0001385
Hypermetropia	Farsightedness Long-sightedness [ more ]	0000540
Hypopigmentation of hair	Loss of hair color	0005599
Hypospadias		0000047
Hypotrophy of the small hand muscles	Degeneration of small hand muscles	0006006
Joint hyperflexibility	Joints move beyond expected range of motion	0005692
Joint hypermobility	Double-Jointed Flexible joints Increased mobility of joints [ more ]	0001382
Kyphosis	Hunched back Round back [ more ]	0002808
Macrotia	Large ears	0000400
Microdontia	Decreased width of tooth	0000691
Narrow palate	Narrow roof of mouth	0000189
Narrow palm		0004283
Nasal speech	Nasal voice	0001611
Pear-shaped nose		0000447
Poor speech		0002465
Positional foot deformity		0005656
Prominent fingertip pads	Prominent finger pads	0001212
Scoliosis		0002650
Seizure		0001250
Slender finger	Narrow fingers Slender fingers thin fingers [ more ]	0001238
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
Ventriculomegaly		0002119
5%-29% of people have these symptoms
Abnormality of dental enamel	Abnormal tooth enamel Enamel abnormalities Enamel abnormality [ more ]	0000682
Aortic aneurysm	Bulge in wall of large artery that carries blood away from heart	0004942
Bicuspid aortic valve	Aortic valve has two leaflets rather than three	0001647
Cataract	Clouding of the lens of the eye Cloudy lens [ more ]	0000518
Cleft palate	Cleft roof of mouth	0000175
Dry skin		0000958
Hydronephrosis		0000126
Hypodontia	Failure of development of between one and six teeth	0000668
Hypotelorism	Abnormally close eyes Closely spaced eyes [ more ]	0000601
Hypothyroidism	Underactive thyroid	0000821
Ichthyosis		0008064
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Pectus excavatum	Funnel chest	0000767
Prominent metopic ridge		0005487
Pyloric stenosis		0002021
Renal duplication	Extra kidney	0000075
Short stature	Decreased body height Small stature [ more ]	0004322
Small for gestational age	Birth weight less than 10th percentile Low birth weight [ more ]	0001518
Spondylolisthesis	Displacement of one backbone compared to another Slipped backbone [ more ]	0003302
Ureteral duplication	Double ureter	0000073
Vertebral fusion	Spinal fusion	0002948
Vesicoureteral reflux		0000076
1%-4% of people have these symptoms
Abnormality of cardiovascular system morphology		0030680
Abnormality of the urinary system	Urinary tract abnormalities Urinary tract abnormality Urinary tract anomalies [ more ]	0000079
Broad chin	Increased width of chin Wide chin [ more ]	0011822
Percent of people who have these symptoms is not available through HPO
Anteverted ears		0040080
Anxiety	Excessive, persistent worry and fear	0000739
Atrial septal defect	An opening in the wall separating the top two chambers of the heart Hole in heart wall separating two upper heart chambers [ more ]	0001631
Autosomal dominant inheritance		0000006
Cleft upper lip	Harelip	0000204
Contiguous gene syndrome		0001466
Eczema		0000964
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Gray matter heterotopia		0002282
Hyperactivity	More active than typical	0000752
Hypoplasia of the corpus callosum	Underdevelopment of part of brain called corpus callosum	0002079
Impulsivity	Impulsive	0100710
Intrauterine growth retardation	Prenatal growth deficiency Prenatal growth retardation [ more ]	0001511
Laryngomalacia	Softening of voice box tissue	0001601
Open mouth	Gaped jawed appearance Gaped mouthed appearance Slack jawed appearance [ more ]	0000194
Pulmonic stenosis	Narrowing of pulmonic valve	0001642
Sacral dimple	Spinal dimple	0000960
Sporadic	No previous family history	0003745
Variable expressivity		0003828
Ventricular septal defect	Hole in heart wall separating two lower heart chambers	0001629
Wide intermamillary distance	Wide-spaced nipples Widely spaced nipples Widely-spaced nipples [ more ]	0006610
Widely spaced teeth	Wide-spaced teeth Widely-spaced teeth [ more ]	0000687

Showing of 104 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 5/1/2020

Do you have updated information on this disease? We want to hear from you.

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

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]^[5]

Last updated: 3/3/2017

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare 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 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.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include Prader-Willi syndrome in the neonatal period and 22q11.2 deletion syndrome, fragile X syndrome, Angelman syndrome and blepharophimosis-intellectual disability syndrome, SBBYS type in older patients. Visit the Orphanet disease page for more information.

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 (CDO)
PO Box 724
Boca Raton, FL 33429
Telephone: +1-561-395-4252
E-mail: https://chromodisorder.org/contact/
Website: https://chromodisorder.org/
Koolen-de Vries Syndrome Foundation
P.O. Box 470218
Fort Worth, TX 76147
Telephone: 1-833-721-KDVS
E-mail: https://kdvsfoundation.org/contact/
Website: https://kdvsfoundation.org/
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: https://www.rarechromo.org/

Social Networking Websites

Visit the Koolen de Vries Europe group on Facebook.

Do you know of an organization? We want to hear from you.

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

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.
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

NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community
May 22, 2020
NCATS Translational Approach Addresses COVID-19
May 21, 2020

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.

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-De Vries syndrome. Orphanet. January, 2009; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96169.