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Koolen de Vries syndrome

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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:
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
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
Drooping lower lip
Outward turned 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 height of face
Increased length of face
Vertical elongation of face
Vertical enlargement of face
Vertical overgrowth 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
Spider fingers
Long slender fingers
[ more ] 		0001166
Conspicuously happy disposition 0100024
Cryptorchidism
Undescended testes
Undescended testis
[ 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, high-arched roof of mouth
Narrow, highly 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
Round back
Hunched 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 |
Last updated: 7/1/2020
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
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
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 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

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

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 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. 

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

Social Networking Websites

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.

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.

  1. Koolen-de Vries syndrome. Genetics Home Reference. 2013; http://ghr.nlm.nih.gov/condition=17q2131microdeletionsyndrome.
  2. Koolen DA & de Vries BBA. KANSL1-Related Intellectual Disability Syndrome. GeneReviews. 2013; https://www.ncbi.nlm.nih.gov/books/NBK24676/.
  3. Koolen DA & cols. Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome. Nat Genet. 2012; 44::639–41.
  4. 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.
  5. Koolen-De Vries syndrome. Orphanet. January, 2009; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96169.