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GENE GUIDE

HNRNPC-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 2025. 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 HNRNPC-Related Syndrome.
a doctor sees a patient

HNRNPC-related syndrome is also called intellectual developmental disorder, autosomal dominant 74. For this webpage, we will be using the name HNRNPC-related syndrome to encompass the wide range of variants observed in the people identified.

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

Key Role

HNRNPC binds and cuts a molecule in the cell called RNA. RNA is made from a DNA sequence and is needed for cell protein production. The HNRNPC gene plays an important role in the development of the brain.

Symptoms

Because the HNRNPC gene is important for the brain, some people may have:

  • Developmental delay
  • Intellectual disability
  • Speech delay
  • Poor or absent speech
  • Delayed walking or inability to walk
  • Lower than average muscle tone (hypotonia) and/or higher than average muscle tone (hypertonia)
  • Seizures
  • Brain changes seen on magnetic resonance imaging (MRI)

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

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

Autosomal dominant conditions

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

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

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

As of 2025, 13 people with HNRNPC-related syndrome have been described in medical research.

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

  • Deep-set eyes
  • Thin upper lip
  • Flat surface of the skin above the upper lip

Scientists and doctors have only just begun to study HNRNPC-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 HNRNPC-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

People with HNRNPC-related syndrome had developmental delay or intellectual disability, gross and fine motor delay, and speech and/or language impairment.

  • 9 out of 9 people had developmental delay or intellectual disability (100 percent)
  • 11 out of 12 people had gross motor delay (92 percent)
  • 12 out of 12 people had fine motor delay (100 percent)
  • 12 out of 12 people had speech and/or language impairment (100 percent)

Behavior

People with HNRNPC-related syndrome had sleep challenges, including sleep apnea, poor concentration, and/or a happy demeanor.

  • 9 out of 12 people had sleep challenges (75 percent)
  • 7 out of 12 people had poor concentration (58 percent)
  • 7 out of 12 people had a happy demeanor (58 percent)
75%
9 out of 12 people had sleep challenges
58%
7 out of 12 people had poor concentration
58%
7 out of 12 people had a happy demeanor

Brain

Some people with HNRNPC-related syndrome had neurological medical issues, including seizures, lower than average muscle tone (hypotonia), a movement disorder, brain changes seen on magnetic resonance imaging (MRI), and a smaller than average head size (microcephaly).

  • 3 out of 13 people had seizures (23 percent)
  • 7 out of 12 people had hypotonia (58 percent)
  • 3 out of 12 people had a movement disorder (25 percent)
  • 10 out of 11 people had brain changes seen on MRI (91 percent)
  • 4 out of 13 people had microcephaly (31 percent)
Human head showing brain outline

Graphs

 
 
 
 
 

100%

80%

60%

40%

20%

0

3 out of 13 people had seizures
7 out of 12 people had hypotonia
3 out of 12 people had a movement disorder
10 out of 11 people had brain changes seen on MRI
4 out of 13 people had microcephaly

Other medical features

People with HNRNPC-related syndrome had feeding issues and/or gastrointestinal issues, shorter than average height, low weight, and recurrent ear infections. Also, 3 people had vision issues that included misaligned eyes and an eye opening that was very small, and 2 people had hearing loss.

  • 7 out of 12 people had feeding difficulties and/or gastrointestinal issues (58 percent)
  • 3 out of 12 people had shorter than average height (25 percent)
  • 1 out of 12 people had low weight (8 percent)
  • 3 out of 12 people had recurrent ear infections (25 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.”

Sources and References

  • Niggl E, Bouman A, Briere LC, et al. HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder. Am J Hum Genet. 2023;110(8):1414-1435. doi:10.1016/j.ajhg.2023.07.005
  • Niggl, E., Bouman, A., Briere, L. C., Hoogenboezem, R. M., Wallaard, I., Park, J., Admard, J., Wilke, M., Harris-Mostert, E., … & van Esbroeck, A. C. M. (2023). HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder. American Journal of Human Genetics, 110(8), 1414-1435. doi:10.1016/j.ajhg.2023.07.005

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