GENE GUIDE

DYRK1A-Related Syndrome

This guide is not meant to take the place of medical advice. Please consult with your doctor about your genetic results and health care choices. This Gene Guide was last updated on 2024. As new information comes to light with new research we will update this page. You may find it helpful to share this guide with friends and family members or doctors and teachers of the person who has DYRK1A-Related Syndrome.
a doctor sees a patient

DYRK1A-related syndrome happens when there are changes to the DYRK1A gene. These changes can keep the gene from working as it should.

Key Role

The DYRK1A gene plays a key role in brain development. It is especially important for creating new brain cells and for updating connections among brain cells.

Symptoms

Because the DYRK1A gene is important in brain development, many people who have DYRK1A-related syndrome have:

  • Intellectual disability
  • Speech delay
  • Motor difficulties
  • Small head, also called microcephaly
  • Feeding problems
  • Vision problems
  • Behavioral issues
  • Seizures
  • Shorter than average height
  • Features of autism

Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the DYRK1A gene: one copy from their mother, from the egg, and one copy from their father, from the sperm. In most cases, parents pass on exact copies of the gene to their child. But the process of copying genes is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both.

Sometimes a random change happens in the sperm or egg. This change to the genetic code is called a ‘de novo’, or new, change. The child can be the first in the family to have the gene change.

De novo changes can take place in any gene. We all have some de novo changes, most of which don’t affect our health. But because DYRK1A plays a key role in development, de novo changes in this gene can have a meaningful effect.

Research shows that DYRK1A-related syndrome is often the result of a de novo change in DYRK1A. Many parents who have had their genes tested do not have the DYRK1A gene change found in their child who has the syndrome. In some cases, DYRK1A-related syndrome happens because the change was passed down from a parent.

Dominant Inheritance

Children have a 50% chance of inheriting the genetic change

Autosomal Dominant Genetic Syndrome

GENE / gene
GENE / gene
Genetic variant that happens in sperm or egg, or after fertilization
GENE / gene
Child with de novo genetic variant
gene / gene
Non-carrier child
gene / gene
Non-carrier child

Why does my child have a change in the DYRK1A gene?

No parent causes their child’s DYRK1A-related syndrome. We know this because no parent has any control over the gene 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 gene change takes place on its own and cannot be predicted or stopped.

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 DYRK1A-related syndrome depends on the genes of both birth parents.

  • If neither birth parent has the same gene change 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 change in the gene.
  • If one birth parent has the same gene change found in their child, the chance of having another child who has the syndrome is 50 percent.

For a symptom-free sibling, a brother or sister, of someone who has DYRK1A-related syndrome, the risk of having a child who has the syndrome depends on the symptom-free sibling’s genes and their parents’ genes.

  • If neither parent has the same gene change found in their child who has the syndrome, the symptom- free sibling has a nearly 0 percent chance of having a child who has DYRK1A-related syndrome.
  • If one birth parent has the same gene change found in their child who has the syndrome, the symptom-free sibling has a small chance of also having the same gene change. If the symptom- free sibling has the same gene change as their sibling who has the syndrome, the symptom-free sibling’s chance of having a child who has DYRK1A-related syndrome is 50 percent.

For a person who has DYRK1A-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, 238 people with DYRK1A-related syndrome have been identified in a medical clinic. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

People who have DYRK1A-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Deep-set eyes that look hooded
  • Narrow forehead
  • Larger than average brow with high hairline
  • Tube-shaped nose
  • Larger than average nasal bridge
  • Lower jaw set back from upper jaw
  • Small chin

Scientists and doctors have only just begun to study DYRK1A-related syndrome. At this point, there are no medicines designed to treat the 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
  • Development 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 DYRK1A-related syndrome should begin as early as possible, ideally before a child begins school.

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.

The section includes medical information on about 81 people with DYRK1A-related syndrome described in research publications.

Speech and Learning

All people with DYRK1A-related syndrome had intellectual disability or developmental delay. Most people had speech delay, and some learned to speak later in development.

  • 81 out of 81 people had intellectual disability or developmental delay (100 percent)
  • 69 out of 77 people had speech delay (90 percent)

Behavior

Autistic features were common, but only about one-half of people met the diagnostic criteria for autism. Many people were hyperactive or had anxiety.

  • 22 out of 62 people had autism (36 percent)
  • 14 out of 43 people had hyperactivity (33 percent)
  • 12 out of 44 people had anxiety (27 percent)
36%
22 out of 62 people had autism.
33%
14 out of 43 people had hyperactivity.
27%
12 out of 44 people had anxiety.

Brain

Almost everyone had a smaller than average head. Seizures were common, as well as brain changes seen on magnetic resonance imaging (MRI).

  • 78 out of 81 people had a smaller than average head size (96 percent)
  • 52 out of 78 people had seizures (67 percent)
  • 26 out of 42 people had abnormal findings on MRI (62 percent)

Growth

Some people with DYRK1A-related syndrome had a diagnosis of microcephaly by the age of 2 and were short in height. Doctors studying DYRK1A-related syndrome have created unique growth charts for children under the age of 5. Share this resource with your doctor to help determine your child’s growth compared with others who have DYRK1A-related syndrome.

  • 30 out of 68 people had short height (44 percent)
  • 33 out of 68 people had a small build and weight below 2 standard deviations (49 percent)
  • 19 out of 39 people were found to have growth restriction when they are developing in pregnancy (49 percent)
44%
30 out of 68 people had short height.
49%
33 out of 68 people had a small build and weight below 2 standard deviations.
49%
19 out of 39 people were found to have growth restriction when they are developing in pregnancy.

Motor concerns

Almost everyone had motor challenges.

  • 52 out of 53 people had motor difficulties, including walking (98 percent)

Feeding and digestion issues

Most people had feeding issues, and some had gastrointestinal issues.

  • 52 out of 55 people had feeding difficulties (95 percent)
  • 14 out of 35 people had gastrointestinal issues (40 percent)

Eyes and ears

Many people had eye defects. About one-half had an unusual shape to their ears, with the outer edge of the ear appearing thick and overfolded.

  • 45 out of 62 people had eye defects (73 percent)

Other issues

Some people had heart defects or issues with their hormones. Many people had skeletal defects.

  • 7 out of 32 people had heart defects (22 percent)
  • 4 out of 14 people had hormone issues (29 percent)
  • 31 out of 45 people had skeletal defects (69 percent)
22%
7 out of 32 people had heart defects.
29%
4 out of 14 people had hormone issues.
69%
31 out of 45 people had skeletal defects.

Where can I find support and resources?

DYRK1A Syndrome International Association

DYRK1A Syndrome International Association (DSIA) will exist to support and maintain a unified community of families and professionals focused on improving the lives of individuals affected by DYRK1A Syndrome. The DYRK1A Syndrome International Association includes organizations & groups throughout the world who are working together to improve the quality of life for those affected by DYRK1A Syndrome. These groups include DYRK1A Syndrome US, the DYRK1A Community UK, the Spanish Syndrome Association DYRK1A, and smaller groups in Italy, Australia, Cyprus, Denmark, France, Poland, and Canada.

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.”

Sources and References

The content in this guide comes from published studies about DYRK1A-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.

  • Bronicki LM. et al. European Journal of Human Genetics, 23, 1482-1487, (2015). Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A www.ncbi.nlm.nih.gov/pubmed/25920557
  • Ji J. et al. European Journal of Human Genetics, 23, 1473-1481, (2015). DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies www.ncbi.nlm.nih.gov/pubmed/25944381
  • Earl RK. et al. Molecular Autism, 8, 54, (2017). Clinical phenotype of ASD-associated DYRK1A haploinsufficiency www.ncbi.nlm.nih.gov/pubmed/29034068
  • Lanvin, P. L., … Vincent, M. (2024). Growth charts in DYRK1A syndrome. American Journal of Medical Genetics Part A, 194(1), 9-16. https://pubmed.ncbi.nlm.nih.gov/37740550/
  • Meissner, L. E., Macnamara, E. F., D’Souza, P., Yang, J., Vezina, G., Ferreira, C. R., Zein, W. M., Tifft, C. J., & Adams, D. R. (2020). DYRK1A pathogenic variants in two patients with syndromic intellectual disability and a review of the literature. Molecular Genetics & Genomic Medicine, 8(12), e1544. https://pubmed.ncbi.nlm.nih.gov/33159716/
  • van Bon, B. W. M., Coe, B. P., de Vries, B. B. A., & Eichler, E. E. DYRK1A Syndrome. 2021 Mar 18. 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/NBK333438/

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