PPM1D-Related Syndrome
PPM1D-related syndrome is also called Jansen-de Vries syndrome (JdVS). For this webpage, we will be using the name PPM1D-related syndrome to encompass the wide range of variants observed in the people identified.
What is PPM1D-related syndrome?
PPM1D-related syndrome happens when there are changes in the PPM1D gene. These changes can keep the gene from working as it should.
Key Role
The PPM1D gene plays a role in deactivating other genes by modifying the shape of chromosomes. Chromosomes are the structures that house DNA within our cells.
Symptoms
Because the PPM1D gene is important for brain activity, many people who have PPM1D-related syndrome have:
- Developmental delay
- Intellectual disability
- Learning challenges
- Language delay
- Autism
- Attention-deficit/hyperactivity disorder (ADHD)
- Anxiety
- Walking challenges
- Recurrent vomiting
- Gastroesophageal reflux disease (GERD)
- High pain threshold
- Short height
What causes PPM1D-related syndrome?
PPM1D-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 PPM1D 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 PPM1D plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that PPM1D-related syndrome is often the result of a de novo variant in PPM1D. Many parents who have had their genes tested do not have the PPM1D genetic variant found in their child who has the syndrome. In some cases, PPM1D-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
PPM1D-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in PPM1D they will likely have symptoms of PPM1D-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 PPM1D gene?
No parent causes their child’s PPM1D-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 PPM1D-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 PPM1D-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 PPM1D-related syndrome, the sibling’s risk of having a child who has PPM1D-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing PPM1D-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit PPM1D-related syndrome.
- If one biological parent has the same genetic variant causing PPM1D-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 PPM1D-related syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have PPM1D-related syndrome?
As of 2026, about 73 people with PPM1D-related syndrome have been identified in a medical clinic.
Do people who have PPM1D-related syndrome look different?
People with PPM1D-related syndrome may look different. Appearance can vary and can include, but is not limited to, these features:
- Low-set ears
- Thin line of the upper lip
- Broad forehead
- Low-set ears
- Short height
- Small hands
How is PPM1D-related syndrome treated?
Scientists and doctors have only just begun to study PPM1D-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 PPM1D-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 PPM1D-related syndrome
Learning and Speech
Most people with PPM1D-related syndrome had developmental delay or intellectual disability, and speech delay or impairment.
- 38 out of 41 people had developmental delay (93 percent)
- 54 out of 61 people had intellectual disability (89 percent)
Behavior
People with PPM1D-related syndrome had behavioral issues, such as features of autism, impulsivity, anxiety, attention-deficit/hyperactivity disorder (ADHD), and aggression.
- 41 out of 60 people had behavioral issues and mood disorders (68 percent)
Brain
Some people with PPM1D-related syndrome had seizures, brain changes seen on magnetic resonance imaging (MRI), lower than average muscle tone (hypotonia), and a smaller than average head size (microcephaly).
- 3 out of 32 people had seizures (9 percent)
- 12 out of 19 people had brain changes seen on MRI (63 percent)
- 41 out of 57 people had hypotonia (72 percent)
- 14 out of 39 people had microcephaly (36 percent)
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Medical and physical concerns linked to PPM1D-related syndrome
Feeding and digestion
People with PPM1D-related syndrome had gastrointestinal issues, such as constipation, feeding difficulties, and gastroesophageal reflux and/or cyclic vomiting syndrome. Triggers for cyclic vomiting syndrome were excessive excitement and sleep deprivation. After episodes of vomiting, some people had light or noise sensitivity.
- 37 out of 52 people had constipation (71 percent)
- 16 out of 21 people had feeding difficulties (76 percent)
- 35 out of 55 people had gastroesophageal reflux and/or vomiting (64 percent)
Vision
More than one-half of people with PPM1D-related syndrome had vision issues like crossed eyes (strabismus), nearsightedness (myopia), and an imperfection of the eye that causes blurred distance and near vision (astigmatism).
- 32 out of 46 people had vision issues (70 percent)
Heart
A few people with PPM1D-related syndrome had heart defects, such as mitral valve prolapse, atrial septal defect, ventricular septal defect, or patent ductus arteriosus.
- 6 out of 12 people had heart defects (50 percent)
Growth
People with PPM1D-related syndrome had growth issues, such as small hands, small feet, short height, and an exaggerated inward curve of the lower spine (hyperlordosis).
- 38 out of 55 people had small hands (69 percent)
- 35 out of 53 people had small feet (66 percent)
- 33 out of 55 people had short height (60 percent)
- 11 out of 17 people had hyperlordosis (65 percent)
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Jansen de Vries Syndrome Foundation
The Jansen de Vries Syndrome Foundation is focused on providing education and resources to both families and medical professionals. Their goal is to raise awareness about this rare genetic condition and unite families, researchers, and medical professionals through the facilitation of a patient registry program. Through fundraising and grant efforts, they will work to provide researchers the resources necessary to gain a better understanding of the PPM1D mutation and develop potential treatments and therapies to ultimately improve the lives of those living with this rare genetic condition.
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 PPM1D – www.simonssearchlight.org/research/what-we-study/ppm1d
Sources and References
- Merida De la Torre, F. J., Porta Pelayo, J., & Ortiz-Martín, I. (2025). Case report: Novel truncating PPM1D variant in a dichorionic diamniotic (DCDA) twin with Jansen-de Vries syndrome. An updated perspective. Frontiers in Genetics, 16, 1601752. doi:10.3389/fgene.2025.1601752
- Pizzol, A., Adams, K. A., de Vries, B. B. A., Curry, C. J., & Calvo, P. L. (2025). Cyclic vomiting syndrome in patients affected by Jansen-de Vries syndrome: Results from an international survey. American Journal of Medical Genetics Part A, 197(3), e63918. doi:10.1002/ajmg.a.63918
- Wojcik, M. H., Srivastava, S., Agrawal, P. B., Balci, T. B., Callewaert, B., Calvo, P. L., Carli, D., Caudle, M., Colaiacovo, S., … & Curry, C. J. (2023). Jansen-de Vries syndrome: Expansion of the PPM1D clinical and phenotypic spectrum in 34 families. American Journal of Medical Genetics Part A, 191(7), 1900-1910. doi:10.1002/ajmg.a.63226