17q21.31 Deletion Syndrome
17q21.31 deletion syndrome is also called Koolen-de Vries syndrome. For this webpage, we will be using the name 17q21.31 deletion syndrome to encompass the wide range of variants observed in the people identified.
What is 17q21.31 deletion syndrome?
17q21.31 deletion syndrome happens when a person is missing a piece of chromosome 17, one of the body’s 46 chromosomes. Chromosomes are structures in our cells that house our genes. The missing piece can affect learning and how the body develops.
17q21.31 deletion syndrome is caused by a deletion in the KANSL1 gene, which is missing when a person has a 17q21.31 deletion. Both 17q21.31 deletion syndrome and KANSL1-related syndrome share the same set of symptoms.
Key Role
The KANSL1 gene in the 17q21.31 region helps to control other genes during brain development.
Symptoms
Because the 17q21.31 region is important for brain activity, many people who have 17q21.31 deletion syndrome have:
- Developmental delay
- Intellectual disability
- Low muscle tone
- Speech and language issues
- Features of autism
- Hyperactivity
- Anxiety
- Seizures
- Brain changes seen on magnetic resonance imaging (MRI)
- Heart or kidney defects
What causes 17q21.31 deletion syndrome?
17q21.31 deletion syndrome is a genetic condition, which means that it is caused by variants in genes. Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the 17q21.31 gene: one copy from their mother’s egg, and one copy from their father’s sperm. In most cases, parents pass on exact copies of the gene to their child. But the process of creating the egg or sperm is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both.
Sometimes a spontaneous variant happens in the sperm, egg or after fertilization. When a brand new genetic variant happens in the genetic code is called a ‘de novo’ genetic variant. The child is usually the first in the family to have the genetic variant.
De novo variants can take place in any gene. We all have some de novo variants, most of which don’t affect our health. But because 17q21.31 plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that 17q21.31 deletion syndrome is often the result of a de novo variant in 17q21.31. Many parents who have had their genes tested do not have the 17q21.31 genetic variant found in their child who has the syndrome. In some cases, 17q21.31 deletion syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
17q21.31 deletion syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in 17q21.31 they will likely have symptoms of 17q21.31 deletion syndrome. For someone with an autosomal dominant genetic syndrome, every time they have a child there is a 50 percent chance they pass on the same genetic variant and a 50 percent chance they do not pass on the same genetic variant.
Autosomal Dominant Genetic Syndrome
What does my child have 17q21.31 deletion syndrome?
No parent causes their child’s 17q21.31 deletion syndrome. We know this because no parent has any control over the chromosome changes that they do or do not pass on to their children. Please keep in mind that nothing a parent does before or during the pregnancy causes this to happen. The genetic change takes place on its own and cannot be predicted or stopped.
What are the chances that other family members or future children will have 17q21.31 deletion syndrome?
Each family is different. A geneticist or genetic counselor can give you advice on the chance that this will happen again in your family.
The risk of having another child who has 17q21.31 deletion syndrome depends on the genes of both biological parents.
- If neither biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is on average 1 percent. This 1 percent chance is higher than the chance of the general population. The increase in risk is due to the very unlikely chance that more of the mother’s egg cells or the father’s sperm cells carry the same genetic variant.
- If one biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is 50 percent.
For a symptom-free brother or sister of someone who has 17q21.31 deletion syndrome, the sibling’s risk of having a child who has 17q21.31 deletion syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing 17q21.31 deletion syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit 17q12 deletion syndrome.
- If one biological parent has the same genetic variant causing 17q21.31 deletion syndrome, the symptom-free sibling has a 50 percent chance of also having the same genetic variant. If the symptom-free sibling has the same genetic variant, their chance of having a child who has the genetic variant is 50 percent.
For a person who has 17q21.31 deletion syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have 17q21.31 deletion syndrome?
As of 2024, over 156 people with 17q21.31 deletion syndrome have been identified in a medical clinic. This includes people with pathogenic or likely pathogenic variants in the KANSL1 gene and people with large deletions that include the KANSL1 gene.
Do people who have 17q21.31 deletion syndrome look different?
People who have 17q21.31 deletion syndrome may look different. Appearance can vary and can include some but not all of these features:
- Long face
- Pear-shaped nose with a round tip
- Large ears
- An opening between the eyelids that is narrow or has an upward slant
- Drooping eyelids
- A skin fold covering the inner corner of the eye
- High forehead
- Unusual hair texture
- Smaller than average teeth size
- Fewer number of teeth than average
- Smaller than average head size
- Short height
How is 17q21.31 deletion syndrome treated?
At this point, there are no medicines designed to treat 17q21.31 deletion syndrome. A genetic diagnosis can help people decide on the best way to track the condition and manage therapies. Doctors can refer people to specialists for:
- Physical exams and brain studies
- Genetics consults
- Developmental and behavior studies
- Other issues, as needed.
A developmental pediatrician, neurologist, or psychologist can follow progress over time and can help:
- Suggest the right therapies. This can include physical, occupational, speech, or behavioral therapy.
- Guide individualized education plans (IEPs).
Specialists advise that therapies for 17q21.31 deletion syndrome should begin as early as possible, ideally before a child begins school.
Your doctor can recommend whether to see an endocrinologist to check for kidney and urinary issues.
If seizures happen, consult a neurologist. There are many types of seizures, and not all types are easy to spot. To learn more, you can refer to resources such as the Epilepsy Foundation’s website: epilepsy.com/learn/types-seizures.
This section includes a summary of information from major published articles. It highlights how many people have different symptoms. To learn more about the articles, see the Sources and References section of this guide.
Behavior and development concerns linked to 17q21.31 deletion syndrome
Speech and learning
Most people with 17q21.31 deletion syndrome had developmental delay and/or intellectual disability, and speech delay. People usually had mild to moderate intellectual disability. Speech issues included oral muscle weakness and apraxia in early childhood. First words were spoken between 2 and a half to 3 and a half years old.
- 129 out of 131 people had developmental delay or intellectual disability (99 percent)
- 109 out of 111 people had speech delay (98 percent)
Behavior
People with 17q21.31 deletion syndrome had behavioral issues, including friendly behavior, features of autism, attention-deficit/hyperactivity disorder (ADHD), or anxiety.
- 103 out of 115 people had friendly behavior (90 percent)
Brain
About one-half of people with 17q21.31 deletion syndrome had seizures and/or brain changes seen on magnetic resonance imaging (MRI). Common seizure types included generalized seizures, unilateral clonic seizures, and focal seizures. Brain changes included ventriculomegaly, aplasia/hypoplasia of the corpus callosum, hydrocephalus, Arnold-Chiari malformation, and intraventricular hemorrhage. Most people had low muscle tone (hypotonia).
- 69 out of 135 people had seizures (51 percent)
- 60 out of 118 people had brain changes seen on MRI (51 percent)
- 122 out of 134 people had hypotonia (91 percent)
Medical and physical concerns linked to 17q21.31 deletion syndrome
Growth
Some people with 17q21.31 deletion syndrome had short height, and they had either intrauterine growth restriction (IUGR) or low birth weight. Some people had a smaller than average head size (microcephaly) or a larger than average head size (macrocephaly).
- 34 out of 104 people had short height (33 percent)
- 38 out of 121 people had IUGR or low birth weight (31 percent)
- 8 out of 102 people had microcephaly (8 percent)
- 15 out of 83 people had macrocephaly (18 percent)
Vision and hearing
The most common eye issues were ptosis (droopy eyelids), strabismus (crossed eyes), and refractive errors (when the shape of the eye causes a blurred image). Some people had hearing impairments.
- 68 out of 114 people had eye issues (60 percent)
- 22 out of 101 people had hearing impairment (22 percent)
Muscle and skeletal issues
People with 17q21.31 deletion syndrome often had musculoskeletal findings, including hypermobile joints, scoliosis/kyphosis (curvature of the spine), or changes in the pectus (breast bone).
- 99 out of 127 people had musculoskeletal findings (78 percent)
- 63 out of 99 people had hypermobile joints (64 percent)
- 40 out of 127 people had scoliosis/kyphosis (32 percent)
- 15 out of 85 people had changes in the pectus (18 percent)
Other medical findings
Some people had heart defects, such as a hole in the heart (atrial septal defect or ventricular septal defect), disease of the heart muscle (cardiomyopathy), or a dilation of the upper part of heart (aortic root dilation).
About one-half of people with 17q21.31 deletion syndrome had genitourinary defects, including cryptorchidism (undescended testicles), hypospadias (when the opening is not at the end of the penis), hydronephrosis/vesicoureteral reflux (when urine has difficulty flowing out the kidney), or kidney duplication.
Some people had hormone issues, including growth hormone issues or precocious puberty. Some people had skin findings.
- 47 out of 132 people had heart defects (36 percent)
- 62 out of 127 people had genitourinary defects (49 percent)
Where can I find support and resources?
KdVS Foundation
To educate, increase awareness and promote research for the support and enrichment of individuals living with Koolen-de Vries Syndrome and their families.
Simons Searchlight
Simons Searchlight is an online international research program, building an ever growing natural history database, biorepository, and resource network of over 175 rare genetic neurodevelopmental disorders. By joining their community and sharing your experiences, you contribute to a growing database used by scientists worldwide to advance the understanding of your genetic condition. Through online surveys and optional blood sample collection, they gather valuable information to improve lives and drive scientific progress. Families like yours are the key to making meaningful progress. To register for Simons Searchlight, go to the Simons Searchlight website at www.simonssearchlight.org and click “Join Us.”
- Learn more about Simons Searchlight: www.simonssearchlight.org/frequently-asked-questions
- Simons Searchlight page on 17q21.31 deletion syndrome: www.simonssearchlight.org/research/what-we-study/17q21-3-deletion
- Simons Searchlight 17q12 deletion syndrome Facebook Community: https://www.facebook.com/groups/17q21.31-deletion
Sources and References
The content in this guide comes from published studies about 17q21.31 deletion syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.
- Karamik, G., Tuysuz, B., Isik, E., Yilmaz, A., Alanay, Y., Sunamak, E. C., Durmusalioglu, E. A., Ozkinay, F., Cetin, G. O., … & Nur, B. (2023). The clinical phenotype of Koolen-de Vries syndrome in Turkish patients and literature review. American Journal of Medical Genetics Part A, 191(7), 1814-1825. https://pubmed.ncbi.nlm.nih.gov/37053206/
- Koolen, D. A., Morgan, A., & de Vries, B. B. A. Koolen-de Vries syndrome. 2023 Feb 2. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK24676/