PSMD12-Related Syndrome
PSMD12-related syndrome is also called Stankiewicz-Isidor syndrome. For this webpage, we will be using the name PSMD12-related syndrome to encompass the wide range of variants observed in the people identified.
What is PSMD12-related syndrome?
PSMD12-related syndrome happens when there are changes in the PSMD12 gene. These changes can keep the gene from working as it should.
Key Role
The PSMD12 gene plays a role in brain development.
Symptoms
Because the PSMD12 gene is important for brain activity, many people who have PSMD12-related syndrome have:
- Developmental delay
- Intellectual disability
- Autism
- Speech delay
- Seizures
- Heart issues
- Low muscle tone
What causes PSMD12-related syndrome?
PSMD12-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 PSMD12 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 PSMD12 plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that PSMD12-related syndrome is often the result of a de novo variant in PSMD12. Many parents who have had their genes tested do not have the PSMD12 genetic variant found in their child who has the syndrome. In some cases, PSMD12-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
PSMD12-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in PSMD12 they will likely have symptoms of PSMD12-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 PSMD12 gene?
No parent causes their child’s PSMD12-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 PSMD12-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 PSMD12-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 PSMD12-related syndrome, the sibling’s risk of having a child who has PSMD12-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing PSMD12-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit PSMD12-related syndrome.
- If one biological parent has the same genetic variant causing PSMD12-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 PSMD12-related syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have PSMD12-related syndrome?
As of 2026, about 52 people with PSMD12-related syndrome have been described in medical research.
Do people who have PSMD12-related syndrome look different?
People who have PSMD12-related syndrome may look different. Appearance can vary and can include some but not all of these features:
- Noticeable forehead
- Small and low-set ears
How is PSMD12-related syndrome treated?
Scientists and doctors have only just begun to study PSMD12-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:
-
- Suggest the right therapies. This can include physical, occupational, speech, or behavioral therapy.
- Guide individualized education plans (IEPs).
Specialists advise that therapies for PSMD12-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 PSMD12-related syndrome
Speech and Learning
Many people with PSMD12-related syndrome had developmental delay or intellectual disability, and speech or language delay.
- 40 out of 51 people had developmental delay or intellectual disability (78 percent)
- 38 out of 51 people had speech or language delay (75 percent)
Behavior
People with PSMD12-related syndrome had behavioral issues, such as autism and attention-deficit/hyperactivity disorder (ADHD).
About 6 in 10 people with PSMD12-related syndrome had behavioral issues.
- 28 out of 49 people had behavioral issues (57 percent)
Graphs
About 6 in 10 people with PSMD12-related syndrome had behavioral issues.
Brain
Some people with PSMD12-related syndrome had neurological medical issues, such as seizures and lower than average muscle tone (hypotonia). Seizures began between the ages of 5 and 13.
- 6 out of 34 people had seizures (18 percent)
- 7 out of 14 people had hypotonia (50 percent)
Medical and physical concerns linked to PSMD12-related syndrome
Heart
People with PSMD12-related syndrome had heart issues, such as changes in the walls of the heart called persistent ductus arteriosus and atrial or ventricular septal defects.
- 17 out of 41 people had heart issues (42 percent)
Kidney and urinary tract
Some people with PSMD12-related syndrome had kidney structure defects, including dilation of the main part of the kidney (pyelectasis), one or both kidneys that fail to develop (kidney agenesis), defects of kidney position, and vesicoureteral reflux.
- 10 out of 31 people had kidney and urinary tract defects (32 percent)
Other developmental features
Many people with PSMD12-related syndrome had vision issues, such as crossed eyes (strabismus) and hand, arm, leg, or feet developmental changes at birth. Some people had hearing loss.
- 20 out of 27 people had vision issues (74 percent)
- 21 out of 32 people had skeletal findings (66 percent)
- 7 out of 40 people had hearing loss (18 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.”
- Learn more about Simons Searchlight: www.simonssearchlight.org/frequently-asked-questions
- Simons Searchlight webpage with more information on PSMD12: www.simonssearchlight.org/research/what-we-study/psmd12
- Simons Searchlight PSMD12 Facebook community: https://www.facebook.com/groups/psmd12
Sources and References
- Feresin, A., Spedicati, B., Zampieri, S., Morgan, A., Magnolato, A., Tesser, A., Tommasini, A., Bonati, M. T., Girotto, G., & Faletra, F. (2025). Does it run in your family? Inherited truncating PSMD12 variants broaden the phenotypic spectrum of Stankiewicz-Isidor syndrome. American Journal of Medical Genetics Part A, 197(4), e63953. doi:10.1002/ajmg.a.63953
- Isidor, B., Ebstein, F., Hurst, A., Vincent, M., Bader, I., Rudy, N. L., Cogne, B., Mayr, J., Brehm, A., … & Stankiewicz, P. (2022). Stankiewicz-Isidor syndrome: Expanding the clinical and molecular phenotype. Genetics in Medicine, 24(1), 179-191. doi:10.1016/j.gim.2021.09.005