GENE GUIDE

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

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

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

Key Role

The PHIP gene plays a key role in cell growth.

Symptoms

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

  • Global developmental delay
  • Intellectual disability
  • Learning disabilities
  • Features of autism
  • Anxiety
  • Aggression
  • Impulsivity
  • Mood disorders
  • Attention-deficit/hyperactivity disorder (ADHD)
  • Low muscle tone
  • Obesity
  • Vision issues

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

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

Autosomal dominant conditions

PHIP-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in PHIP they will likely have symptoms of PHIP-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 do I or my child have a change in the PHIP gene?

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

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

As of 2026, about 103 people in the world with changes in the PHIP gene had been described in medical research. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

People with PHIP-related syndrome may look different. Appearance can vary and can include, but is not limited to, these features:

  • Smaller than average head size, also called microcephaly
  • Low muscle tone, also called hypotonia
  • Noticeable forehead
  • Small jaw, also called micrognathia
  • Round face
  • Long or short space between the nose and lip 
  • Large ears
  • Thick earlobes
  • Thick eyebrows
  • Arched eyebrows that meet in the center of the forehead
  • Skin folds at the eyes, also called epicanthal folds
  • Small nose
  • Upturned nose
  • Thin lips
  • Roof of mouth with a high arch
  • Toes that are webbed or joined, also called syndactyly
  • Tapering fingers
  • Spots of different pigmentation on the skin

Scientists and doctors have only just begun to study PHIP-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 PHIP-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 two 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.

Learning and speech

Most people with PHIP-related syndrome had mild to severe developmental delay or intellectual disability. Some people had speech delay or impairment, and a few people had typical development.

  • 94 out of 103 people had developmental delay or intellectual disability (91 percent)

Behavior

People with PHIP-related syndrome had behavioral issues, such as features of autism, impulsivity, anxiety, attention-deficit/hyperactivity disorder (ADHD), and aggression. Some people with PHIP-related syndrome had sleeping issues.

  • 74 out of 99 people had behavioral issues and mood disorders (75 percent)
  • 30 out of 96 people had sleeping issues (31 percent)

Brain

A few people with PHIP-related syndrome had seizures, whereas more than one-half of people had lower than average muscle tone (hypotonia).

  • 8 out of 93 people had seizures (9 percent)
  • 51 out of 93 people had hypotonia (55 percent)
9%
8 out of 93 people had seizures.
55%
51 out of 93 people had hypotonia.

Mobility

Less than one-third of people with PHIP-related syndrome had clumsiness/coordination disorder. A few people with PHIP-related syndrome had movement disorders including tremors.

  • 22 out of 73 people had clumsiness/coordination disorder (30 percent)
  • 10 out of 47 people had movement disorders (21 percent)

Vision

More than one-half of people with PHIP-related syndrome had vision issues like crossed eyes (strabismus), nearsightedness (myopia), and farsightedness (hyperopia).

  • 61 out of 98 people had vision issues (62 percent)

Feeding and digestion

Some people with PHIP-related syndrome had gastrointestinal issues, such as constipation and gastroesophageal reflux disease (GERD). One-third of people with PHIP-related syndrome had feeding difficulty during the neonatal period.

  • 34 out of 94 people had constipation (36 percent)
  • 11 out of 47 people had gastroesophageal reflux disease (23 percent)
  • 31 out of 93 people had neonatal feeding difficulties (33 percent)
36%
34 out of 94 people had constipation.
23%
11 out of 47 people had gastroesophageal reflux disease.
33%
31 out of 93 people had neonatal feeding difficulties.

Growth

About two-thirds of people with PHIP-related syndrome were overweight or obese. Some males with PHIP-related syndrome had undescended testicles, also called cryptorchidism.

  • 66 out of 100 people were overweight or obese (66 percent)
  • 31 out of 96 people had cryptorchidism (32 percent)

Where can I find support and resources?

Chung-Jansen Syndrome Foundation

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 PHIP-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.

  • Loid, P., Vuorela, N., Aaltonen, K., Kuittinen, J., & Mäkitie, O. (2026). Novel insights: A novel PHIP variant in a family with severe early-onset obesity. Hormone Research in Paediatrics, 99(1), 49-56. doi:10.1159/000542205
  • Pascolini, G., Scaglione, G. L., Chandramouli, B., Castiglia, D., Di Zenzo, G., & Didona, B. (2024). Broadening the PHIP-associated neurodevelopmental phenotype. Children (Basel), 11(11), 1395. doi:10.3390/children11111395
  • Sudnawa, K. K., Calamia, S., Geltzeiler, A., & Chung, W. K. (2024). Clinical phenotypes of individuals with Chung-Jansen syndrome across age groups. American Journal of Medical Genetics Part A, 194(3), e63471. doi:10.1002/ajmg.a.63471