SYNCRIP-Related Syndrome
SYNCRIP-related syndrome is also called SYNCRIP related neurodevelopmental disorder (SYNCRIP-RNDD). For this webpage, we will be using the name SYNCRIP-related syndrome to encompass the wide range of variants observed in the people identified.
What is SYNCRIP-related syndrome?
SYNCRIP-related syndrome happens when there are changes in the SYNCRIP gene. These changes can keep the gene from working as it should.
Key Role
The SYNCRIP gene plays a key role in the development of the brain, heart, and eyes.
Symptoms
Because the SYNCRIP gene is important for brain activity, many people who have SYNCRIP-related syndrome have:
- Developmental delay, or intellectual disability, or both
- Autism spectrum disorder or features of autism
- Seizures
- Brain changes seen on magnetic resonance imaging (MRI)
- Low muscle tone, also called hypotonia
- Eye or vision issues
- Heart defects
- Behavioral issues, including attention-deficit/hyperactivity disorder (ADHD) and self-injury behavior
- Feeding issues
- Sensorineural hearing loss
- Genitourinary defects
- Gastrointestinal issues
What causes SYNCRIP-related syndrome?
SYNCRIP-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 SYNCRIP 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 SYNCRIP plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that SYNCRIP-related syndrome is often the result of a de novo variant in SYNCRIP. Many parents who have had their genes tested do not have the SYNCRIP genetic variant found in their child who has the syndrome. In some cases, SYNCRIP-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
SYNCRIP-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in SYNCRIP they will likely have symptoms of SYNCRIP-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 SYNCRIP gene?
No parent causes their child’s SYNCRIP-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 SYNCRIP-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 SYNCRIP-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 SYNCRIP-related syndrome, the sibling’s risk of having a child who has SYNCRIP-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing SYNCRIP-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit SYNCRIP-related syndrome.
How many people have SYNCRIP-related syndrome?
As of 2025, over 30 people with SYNCRIP-related syndrome have been identified in medical research.
Do people who have SYNCRIP-related syndrome look different?
People who have SYNCRIP-related syndrome may look different. Facial features can include some or all of the following:
- Noticeable forehead
- Low-set ears that are rotated backwards
- Upward tilt of the nostrils
- Wide eyebrows
- Skin folds at the eyes, also called epicanthal folds
How is SYNCRIP-related syndrome treated?
Scientists and doctors have only just begun to study SYNCRIP-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 SYNCRIP-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 SYNCRIP-related syndrome
Speech and learning
Most people with SYNCRIP-related syndrome had global developmental delay and/or intellectual disabilities, from mild to profound.
- 26 out of 30 people had global developmental delay and/or intellectual disability (87 percent)
- 17 out of 26 people had speech and/or language delay (65 percent)
Behavior
People with SYNCRIP-related syndrome had behavioral issues, such as autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), aggression, anxiety, or sleep disturbance.
- 17 out of 29 people had autism spectrum disorder (59 percent)
- 5 out of 25 people had ADHD (20 percent)
- 2 out of 25 people had aggression (8 percent)
Brain
People with SYNCRIP-related syndrome had low muscle tone (hypotonia), changes seen on magnetic resonance imaging (MRI), seizures, and larger-than-average head size (macrocephaly).
- 9 out of 23 people had hypotonia (39 percent)
- 10 out of 25 people had changes seen on MRI (40 percent)
- 7 out of 28 people had seizures (25 percent)
- 3 out of 25 people had macrocephaly (12 percent)
Medical and physical concerns linked to SYNCRIP-related syndrome
Mobility
Some people who have SYNCRIP-related syndrome had a movement disorder, including poor balance, cerebral palsy, involuntary movements, poor muscle control that causes clumsy movements (ataxia), and walking issues.
- 8 out of 25 people had a movement disorder (32 percent)
- 5 out of 25 people had walking issues (20 percent)
Vision
People with SYNCRIP-related syndrome had crossed eyes (strabismus), nearsightedness, cortical visual impairment, damage to the optic nerve (optic atrophy), and uncontrolled eye movements (nystagmus).
- 8 out of 25 people had strabismus (32 percent)
Kidney and genital
Exactly 1 in 5 people had defects of the kidneys and/or genitalia, such as having cystic kidneys or having only one kidney.
- 5 out of 25 people had defects of the kidneys and/or genitalia (20 percent)
Where can I find support and resources?
HNRNP Family Foundation
The HNRNP Family Foundation is dedicated to improving the lives of patients and families around the world that live with rare HNRNP-Related Neurodevelopmental Disorders (HNRNP-RNDDs). They work closely with dedicated scientists and the medical community to drive patient-centered research. They are committed to finding treatments and creating a neurodiverse affirming community through education and support.
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 SYNCRIP – www.simonssearchlight.org/research/what-we-study/syncrip
- Simons Searchlight HNRNPU Facebook community – https://www.facebook.com/groups/syncrip
Sources and References
The content in this guide comes from a published study about SYNCRIP-related syndrome. Below you can find details about the study.
- Semino, F., Schröter, J., Willemsen, M. H., Bast, T., Biskup, S., Beck-Woedl, S., Brennenstuhl, H., Schaaf, C. P., Kölker, S., … & Syrbe, S. (2021). Further evidence for de novo variants in SYNCRIP as the cause of a neurodevelopmental disorder. Human Mutation, 42(9), 1094-1100. https://onlinelibrary.wiley.com/doi/10.1002/humu.24245
- Gillentine, M. A., Wang, T., Hoekzema, K., Rosenfeld, J., Liu, P., Guo, H., Kim, C. N., De Vries, B. B. A., Vissers, L., … & Eichler, E. E. (2021). Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders. Genome Medicine, 13(1), 63. https://pmc.ncbi.nlm.nih.gov/articles/PMC8056596/