GENE GUIDE

YY1-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 in 2025. 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 YY1-Related Syndrome.
a doctor sees a patient

YY1-related syndrome is also called Gabriele-de Vries syndrome. For this webpage, we will be using the name YY1-related syndrome to encompass the wide range of variants observed in the people identified.

YY1-related syndrome happens when there are changes in the YY1 gene. These changes can keep the gene from working as it should.

Key Role

YY1 plays different roles in the body, including in development before birth and in the development, growth, and division of cells.

Symptoms

Because the YY1 gene is important for brain activity, many people who have YY1-related syndrome have:

  • Developmental delay
  • Intellectual disability
  • Attention-deficit/hyperactivity disorder (ADHD)
  • Anxiety disorders
  • Autism spectrum disorder
  • Speech delay
  • Walking defects
  • Brain changes seen on magnetic resonance imaging (MRI)

YY1-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 YY1 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 YY1 plays a key role in development, de novo variants in this gene can have a meaningful effect.

Research shows that YY1-related syndrome is often the result of a de novo variant in YY1. Many parents who have had their genes tested do not have the YY1 genetic variant found in their child who has the syndrome. In some cases, YY1-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

YY1-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in YY1 they will likely have symptoms of YY1-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

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

No parent causes their child’s YY1-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 foreseen 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 YY1-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 YY1-related syndrome, the sibling’s risk of having a child who has YY1-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing YY1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit YY1-related syndrome. 
  • If one biological parent has the same genetic variant causing YY1-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 YY1-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, at least 37 people with YY1-related syndrome have been identified in a medical clinic.

People who have YY1-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Wide forehead
  • Fullness in the upper eyelids
  • Round nose
  • Pointed chin
  • Tooth defects

Scientists and doctors have only just begun to study YY1-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 YY1-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.

Speech and learning

Most people with YY1-related syndrome had developmental delays, intellectual disabilities, and delayed development of speech.

  • 23 out of 27 people had intellectual disability (85 percent)
  • 28 out of 29 people had delayed speech (97 percent)

Behavior

People with YY1-related syndrome had behavioral challenges, such as autism, attention-deficit/hyperactivity disorder (ADHD), anxiety, or schizoaffective disorder.

  • 18 out of 27 people had behavioral challenges (67 percent)

Brain

Some people with YY1-related syndrome had lower than average muscle tone (hypotonia) and brain changes seen on magnetic resonance imaging (MRI).

  • 13 out of 28 people had hypotonia (46 percent)
  • 11 out of 22 people had brain changes seen on MRI (50 percent)
46%
13 out of 28 people had hypotonia
50%
11 out of 22 people had brain changes seen on MRI

Physical findings

People with YY1-related syndrome had heart, eye, and skeletal defects.

  • 5 out of 23 people had heart findings (22 percent)
  • 17 out of 24 people had eye defects (72 percent)
  • 22 out of 26 people had skeletal defects (85 percent)
22%
5 out of 23 people had heart findings
72%
17 out of 24 people had eye defects
85%
22 out of 26 people had skeletal defects

Other medical features

Feeding difficulties were common for people with YY1-related syndrome, and about 1 in 5 people had recurrent infections.

  • 22 out of 26 people had feeding difficulties (85 percent)
  • 5 out of 22 people had recurrent infections (23 percent)

Where can I find support and resources?

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

  • Yang, J., Yu, C., Lyn, N., Liu, L., Li, D., & Shang, Q. (2024). Clinical analysis of Gabriele-de Vries caused by YY1 mutations and literature review. Molecular Genetics & Genomic Medicine, 12(1), e2281. https://pmc.ncbi.nlm.nih.gov/articles/PMC10767417/
  • Khamirani, H. J., Zoghi, S., Namdar, Z. M., Kamal, N., Dianatpour, M., Tabei, S. M. B., Mohammadi, S., Dehghanian, F., Farbod, Z., & Dastgheib, S. A. (2022). Clinical features of patients with Yin Yang 1 deficiency causing Gabriele-de Vries syndrome: A new case and review of the literature. Annals of Human Genetics, 86(1), 52-62. https://pubmed.ncbi.nlm.nih.gov/34729769/

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