GENE GUIDE

POGZ-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 POGZ-Related Syndrome.
a doctor sees a patient

POGZ-related syndrome is also called White-Sutton syndrome. For this webpage, we will be using the name POGZ-related syndrome to encompass the wide range of variants observed in the people identified.

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

Key Role

The POGZ gene plays a role in brain development.

Symptoms

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

  • Feeding difficulties
  • Lower than average muscle tone
  • Smaller than average head size
  • Sleeping issues
  • Developmental delay
  • Intellectual disability
  • Autistic features
  • Self injurious behavior
  • Vision issues

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

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

Autosomal dominant conditions

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

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

  • If neither parent has the same genetic variant causing POGZ-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit POGZ-related syndrome. 

As of 2024, at least 162 people with POGZ-related syndrome have been identified in a medical clinic.

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

  • Lower than average muscle tone
  • Smaller than average head size
  • Shorter than average height
  • Low-set ears
  • Pointed chin
  • Eyes that are not aligned
  • Open mouth

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

Speech and Learning

All people with POGZ-related syndrome had developmental delay or intellectual disability and speech delays.

  • 76 out of 76 people had developmental delay or intellectual disability (100 percent)
  • 74 out of 74 had speech delays (100 percent)

Behavior

Some people with POGZ-related syndrome had autism and other behavioral challenges. Behavioral issues include biting and aggression, anxiety, stereotype behavior, withdrawal, hyperactivity, and obsessions. 

  • 33 out of 73 people had ADHD (45 percent)
  • 46 out of 78 people had behavioral issues (59 percent)
45%
33 out of 73 people had ADHD.
59%
46 out of 78 people had behavioral issues.

Brain

A few people with POGZ-related syndrome had seizures and sleep disorders. Brain changes were observed on magnetic resonance imaging (MRI) for about 2 out of 3 people, mostly variable or nonspecific findings.

  • 11 out of 71 people had seizures (15 percent)
  • 18 out of 63 people had sleep disorders (29 percent)
Human head showing brain outline

Mobility

Many people had movement issues, such as motor delays, as well as low muscle tone, also called hypotonia. Musculoskeletal defects included minor abnormalities of the fingers and toes; relaxed joints; club feet; contracted joints; and fingers or toes that are webbed or joined, also called syndactyly.

  • 61 out of 76 people had motor delay (80 percent)
  • 34 out of 44 people had hypotonia (77 percent)
  • 22 out of 71 people had musculoskeletal defects (31 percent)
80%
61 out of 76 people had motor delay.
77%
34 out of 44 people had hypotonia.
31%
22 out of 71 people had musculoskeletal defects.

Feeding and digestion

People with POGZ-related syndrome sometimes had feeding difficulties, constipation, cyclic vomiting, diaphragmatic hernia, or other gastrointestinal disorders. Some people required nasogastric tube feeding or gastrostomy. For those with cyclic vomiting, symptoms tended to resolve with age.

  • 23 out of 44 people had feeding difficulties (52 percent)
  • 17 out of 56 people had constipation (30 percent)
  • 11 out of 52 people had cyclic vomiting (21 percent)
  • 6 out of 71 people had other gastrointestinal issues (8 percent)
52%
23 out of 44 people had feeding difficulties.
30%
17 out of 56 people had constipation.
21%
11 out of 52 people had cyclic vomiting.
8%
6 out of 71 people had other gastrointestinal issues.

Other features

Many people had vision issues, and less commonly, hearing loss. Vision issues included but were not limited to retinal dystrophy, which is an underdeveloped optic nerve.

  • 40 out of 64 people had vision issues (63 percent)
  • 28 out of 74 people had hearing loss (38 percent)

A few people had genitourinary defects.

  • 5 out of 48 people had urinary tract defects (10 percent)
  • 6 out of 51 males had genital defects (12 percent)

Where can I find support and resources?

White Sutton Syndrome Foundation 

The mission of the White Sutton Syndrome Foundation is to build a community that will improve the quality of life for those diagnosed with White Sutton Syndrome and their families, to educate others about this condition and to fund research in order to better understand its symptoms, treatments and prognosis.

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

  • Batzir, N. A., White, J., & Sutton, V. R. White-Sutton syndrome. 2021 Sep 16. 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/NBK573972/
  • Nagy, D., Verheyen, S., Wigby, K. M., Borovikov, A., Sharkov, A., Slegesky, V., Larson, A., Fagerberg, C., Brasch-Andersen, C., … Weis, D. (2022). Genotype-phenotype comparison in POGZ-related neurodevelopmental disorders by using clinical scoring. Genes (Basel), 13(1). https://pubmed.ncbi.nlm.nih.gov/35052493/

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