GENE GUIDE

ZNF292-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 ZNF292-Related Syndrome.
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ZNF292-related syndrome happens when there are changes to the ZNF292 gene. These changes can keep the gene from working as it should.

Key Role

The ZNF292 gene plays a key role in brain growth.

Symptoms

Because the ZNF292 gene is important in the development and function of brain cells, people who have ZNF292-related syndrome have:

  • Intellectual disability
  • Speech delay
  • Autism
  • Brain changes observed on magnetic resonance imaging (MRI)
  • Attention deficit hyperactivity disorder, or ADHD
  • Epilepsy
  • Poor feeding and constipation
  • Failure to thrive

ZNF292-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 ZNF292 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 ZNF292 plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that ZNF292-related syndrome is often the result of a de novo variant in ZNF292. Many parents who have had their genes tested do not have the ZNF292 genetic variant found in their child who has the syndrome. In some cases, ZNF292-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

ZNF292-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in ZNF292 they will likely have symptoms of ZNF292-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

Why does my child have a change in the ZNF292 gene?

No parent causes their child’s ZNF292-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 ZNF292-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 ZNF292-related syndrome, the sibling’s risk of having a child who has ZNF292-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing ZNF292-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit ZNF292-related syndrome. 
  • If one biological parent has the same genetic variant causing ZNF292-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 ZNF292-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, at least 80 people with ZNF292-related syndrome have been identified in a medical clinic. The first case of ZNF292-related syndrome was described in 2019. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

People who have ZNF292-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • A very small lower jaw
  • Widely spaced eyes
  • Lower-set ears
  • Shorter than average height
  • Lower or higher than average muscle tone

Scientists and doctors have only just begun to study ZNF292-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 ZNF292-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/…t-is-epilepsy/seizure-types

This section includes a summary of information from a major published article describing 20 people who have ZNF292-related syndrome. It highlights how many people have different symptoms. To learn more about the article, see the Sources and references section of this guide.

Learning

Almost everyone studied to date who had ZNF292-related syndrome had intellectual disability or developmental delay.

Mild delays were most common, followed by moderate, and severe delays.

  • 11 out of 27 people had mild delays.
  • 6 out of 27 people had moderate delays.
  • 3 out of 27 people had severe delays.
41%
11 out of 27 people had mild delays.
22%
6 out of 27 people had moderate delays.
11%
3 out of 27 people had severe delays.

Speech

Almost everyone had speech delays.

  • 26 out of 27 people had speech delays (96 percent).

Behavior

More than one-half had autism or symptoms of autism. One-third had attention deficit hyperactivity disorder, also called ADHD.

  • 17 out of 27 people had autism (63 percent).
  • 9 out of 27 people had ADHD (33 percent).
63%
17 out of 27 people had autism. 
33%
9 out of 27 people had ADHD. 

Muscle tone

About one-half had changes in muscle tone, including low muscle tone or tight or stiff muscles.

  • 13 out of 27 people had changes in muscle tone (48 percent).

Brain

Of those who had a medical test called an MRI that looks at the structure of the brain, about one-half had changes in brain structure.

  • 9 out of 17 people had changes in brain seizures (53 percent).

Growth

More than one-third had slow growth or short height.

  • 11 out of 27 people had slow growth or short height (41 percent).

Feeding and digestion issues

Less than one-third had feeding issues.

  • 8 out of 26 people had feeding issues (31 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

The content in this guide comes from a published study about ZNF292-related syndrome. Below you can find details about the study, as well as a link to the full article.

  • Mirzaa GM. et al. Genetics in Medicine, 22, 538-546, (2020). De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder www.ncbi.nlm.nih.gov/pmc/articles/PMC7060121

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