WAC-Related Syndrome
WAC-related syndrome is also called DeSanto-Shinawi syndrome or WAC-related intellectual disability. For this webpage, we will be using the name WAC-related syndrome to encompass the wide range of variants observed in the people identified.
What is WAC-related syndrome?
WAC-related syndrome happens when there are changes in the WAC gene. These changes can keep the gene from working as it should.
Key Role
The WAC protein plays an important role in repairing DNA after it’s damaged.
Symptoms
Because the WAC gene is important for brain activity, many people who have WAC-related syndrome have:
- Developmental delay
- Intellectual disability
- Delayed development of speech
- Seizures
- Autism
- Brain changes seen on magnetic resonance imaging (MRI)
- Attention-deficit/hyperactivity disorder (ADHD)
- Anxiety
- Aggression and self-injury behaviors
- Feeding issues and constipation
- Heart structure defects
- Low muscle tone
- Respiratory issues
What causes WAC-related syndrome?
WAC-related 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 WAC 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 WAC plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that WAC-related syndrome is often the result of a de novo variant in WAC. Many parents who have had their genes tested do not have the WAC genetic variant found in their child who has the syndrome. In some cases, WAC-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
WAC-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in WAC they will likely have symptoms of WAC-related 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
Why does my child have a change in the WAC gene?
No parent causes their child’s WAC-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.
What are the chances that other family members or future children will have WAC-related 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 WAC-related 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 WAC-related syndrome, the sibling’s risk of having a child who has WAC-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing WAC-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit WAC-related syndrome.
- If one biological parent has the same genetic variant causing WAC-related 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 WAC-related syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have WAC-related syndrome?
As of 2025, about 102 people with WAC-related syndrome have been identified in a medical clinic.
Do people who have WAC-related syndrome look different?
People with WAC-related syndrome may look different. Appearance can vary and can include some but not all of these features:
- Wide forehead
- Full cheeks
- Ears that are missing some of the regular grooves
- Eye and vision issues
- Thin upper lip
How is WAC-related syndrome treated?
Scientists and doctors have only just begun to study WAC-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:
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- 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:
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- Suggest the right therapies. This can include physical, occupational, speech, or behavioral therapy.
- Guide individualized education plans (IEPs).
Specialists advise that therapies for WAC-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: www.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 WAC-related syndrome
Speech and learning
Many people with WAC-related syndrome had intellectual disability and speech and/or language impairment.
- 25 out of 33 people had intellectual disability (76 percent)
- 35 out of 37 people had speech and/or language impairment (95 percent)
Behavior
People with WAC-related syndrome had behavioral issues, such as features of autism, attention-deficit/hyperactivity disorder (ADHD), hyperactivity, anxiety, or sleep challenges.
- 13 out of 36 people had autism or features of autism (36 percent)
- 11 out of 30 people had ADHD (37 percent)
- 10 out of 35 people had hyperactivity (29 percent)
- 16 out of 37 people had anxiety (43 percent)
- 14 out of 30 people had sleep challenges (47 percent)
Graphs
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Brain
Some people with WAC-related syndrome had neurological medical issues, including seizures, low muscle tone (hypotonia), and brain changes seen on magnetic resonance imaging (MRI).
- 10 out of 34 people had seizures (29 percent)
- 13 out of 37 people had hypotonia (35 percent)
- 11 out of 23 people had brain changes seen on MRI (48 percent)
Medical and physical concerns linked to WAC-related syndrome
Vision and hearing
One-half of people with WAC-related syndrome had vision issues, and some had hearing loss. Vision issues included crossed eyes (strabismus), farsightedness (hyperopia) or nearsightedness (myopia), cortical visual impairment, or an imperfection of the eye that causes blurred distance and near vision (astigmatism).
- 16 out of 32 people had vision issues (50 percent)
- 4 out of 14 people had hearing loss (29 percent)
Heart
Rarely, people with WAC-related syndrome had heart issues, such as a hole between the left and right upper chambers of the heart (patent foramen ovale) or other changes in the walls of the heart.
2 in 12 people with WAC-related syndrome had heart defects.
- 2 out of 12 people had heart issues (17 percent)
Graphs
Gastrointestinal and feeding
Constipation and gastroesophageal reflux disease (GERD) were common in people with WAC-related syndrome. About one-half of people had feeding issues.
- 13 out of 22 people had gastrointestinal issues (59 percent)
- 12 out of 28 people had feeding issues (43 percent)
Where can I find support and resources?
The DESSH Foundation
The DESSH Foundation was established to raise awareness of DeSanto-Shinawi Syndrome, advance research, and provide a community of support for families challenged by DESSH.
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 webpage with more information on WAC – www.simonssearchlight.org/research/what-we-study/wac
- Simons Searchlight Facebook Group – https://www.facebook.com/groups/wac
Sources and References
- Blázquez, A., Rodriguez-Revenga, L., Alvarez-Mora, M. I., & Calvo, R. (2025). Clinical and genetic findings in autism spectrum disorders analyzed using exome sequencing. Frontiers in Psychiatry, 16, 1515793. doi:10.3389/fpsyt.2025.1515793
- Dwivedi, A., Chauhan, L., Kumar, P., Nanda, A., & Jayakrishnan, V. Y. (2025). Novel WAC gene variant identified in the first documented case of DeSanto-Shinawi syndrome in India. Molecular and Cellular Pediatrics, 12(1), 7. doi:10.1186/s40348-025-00193-1
- Pasquali, D., Torella, A., Grandone, A., Luongo, C., Morleo, M., Peduto, C., di Fraia, R., Selvaggio, L. D., Allosso, F., … & Nigro, V. (2023). Patients with DeSanto-Shinawi syndrome: Further extension of phenotype from Italy. American Journal of Medical Genetics Part A, 191(3), 823-830. doi:10.1002/ajmg.a.63061
- Varvagiannis, K., de Vries, B. B. A., & Vissers, L. E. L. M. WAC-related intellectual disability. 2017 Nov 30. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK465012/