HNRNPK-Related Syndrome
HNRNPK-related syndrome is also called Au-Kline syndrome. For this webpage, we will be using the name HNRNPK-related syndrome to encompass the wide range of variants observed in the people identified.
What is HNRNPK-related syndrome?
HNRNPK-related syndrome happens when there are changes in the HNRNPK gene. These changes can keep the gene from working as it should.
Key Role
The HNRNPK gene may play an important role in human development.
Symptoms
Because the HNRNPK gene might be important in the development and function of brain cells, many people who have HNRNPK-related syndrome have:
- Developmental delay
- Intellectual disability
- Delays or difficulty in speaking
- Heart defects
- Kidneys that cannot fully empty causing them to swell with urine, also called hydronephrosis
- Feeding difficulties
- Hip joints that have not formed properly, also called hip dysplasia
- Growth issues such as shorter than average height
- Low muscle tone
- Sideways curve of the spine, also called scoliosis
- Hearing loss
What causes HNRNPK-related syndrome?
HNRNPK-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 HNRNPK 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 HNRNPK plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that HNRNPK-related syndrome is often the result of a de novo variant in HNRNPK. Many parents who have had their genes tested do not have the HNRNPK genetic variant found in their child who has the syndrome. In some cases, HNRNPK-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
HNRNPK-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in HNRNPK they will likely have symptoms of HNRNPK-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 HNRNPK gene?
No parent causes their child’s HNRNPK-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 HNRNPK-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 1HNRNPK-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 16p11.2 duplication syndrome, the sibling’s risk of having a child who has HNRNPK-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing HNRNPK-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit HNRNPK-related syndrome.
- If one biological parent has the same genetic variant causing HNRNPK-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 HNRNPK-related syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have HNRNPK-related syndrome?
As of 2025, about 76 people in the world with an HNRNPK genetic variant have been included in medical research.
Do people who have HNRNPK-related syndrome look different?
People with HNRNPK-related syndrome may look different. Appearance can vary and can include, but are not limited to, these features:
- Lower than average muscle tone
- Underdeveloped ear shape
- Openings or splits in the roof of the mouth, also called cleft palate
- Joining of the skull bones during infancy, also called craniosynostosis
- Toes that overlap
- Depression in the center of the chest
- Sideways curve of the spine, also called scoliosis
How is HNRNPK-related syndrome treated?
Scientists and doctors have only just begun to study HNRNPK-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 HNRNPK-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 HNRNPK-related syndrome
Researchers think that people who have HNRNPK-related syndrome that is caused by a problematic missense variant might less often have abnormal organ formation, growth, or developmental delays than those with loss-of-function variants.
The summary below includes people who have any HNRNPK damaging genetic variant. Additional studies with more people who have HNRNPK-related syndrome are needed to better understand the different HNRNPK variants.
Speech and learning
All people with HNRNPK-related syndrome had developmental delay or intellectual disability (ID), and speech delays or impairment. Most people studied had verbal communication with single words or phrases, but most people also used sign language or communication devices.
- 33 out of 33 people had developmental delay or ID (100 percent)
Behavior
People with HNRNPK-related syndrome had behavioral issues, such as autism, attention-deficit/hyperactivity disorder (ADHD), anxiety, obsessive-compulsive disorder, and impulse control.
- 2 out of 13 people had autism (15 percent)
- 2 out of 14 people had ADHD (14 percent)
- 2 out of 14 people had anxiety (14 percent)
- 1 out of 14 people had obsessive-compulsive disorder (7 percent)
- 1 out of 14 people had impulse control (7 percent)
Graphs
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80%
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40%
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Brain
Some people with HNRNPK-related syndrome had neurological medical issues, including seizures, brain changes seen on magnetic resonance imaging (MRI), lower than average muscle tone (hypotonia), and a high pain tolerance.
- 32 out of 32 people had hypotonia (100 percent)
- 16 out of 31 people had brain changes seen on MRI (52 percent)
- 11 out of 30 people had high pain tolerance (37 percent)
Medical and physical concerns linked to HNRNPK-related syndrome
Growth
About 1 in 3 people with HNRNPK-related syndrome often had growth issues, including having a shorter than average height and difficulty gaining weight. People also had a sideways curve of the spine (scoliosis) and hip joints that did not form properly (hip dysplasia).
- 13 out of 32 people had scoliosis (41 percent)
Heart
People with HNRNPK-related syndrome had heart defects. Conditions most commonly reported were ventricle septal defect, and rarely, complex heart defects, aortic dilation, and left ventricular non-compaction cardiomyopathy.
About 6 in 10 people with HNRNPK-related syndrome had heart defects.
- 21 out of 33 people had heart defects (64 percent)
Graphs
21 out of 33 people had heart defects (64 percent)
Genitourinary
About one-half of people had kidneys that could not fully empty causing them to swell with urine, also called hydronephrosis. Males often had undescended testicles (cryptorchidism).
- 16 out of 31 people had hydronephrosis (52 percent)
- 13 out of 17 males had undescended testicles (76 percent)
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 HNRNPK – www.simonssearchlight.org/research/what-we-study/hnrnpk
Sources and References
- Au, P. Y. B., McNiven, V., Phillips, L., Innes, A. M., & Kline, A. D. Au-Kline syndrome. 2024 Feb 1. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK540283/
- Mingoia, M., Meloni, A., Sedda, S., Choufani, S., Asunis, I., Gemma, G., Ammendola, A., Torabi-Marashi, A., di Venere, E., … & Angius, A. (2025). A novel intronic variant in the KH3 domain of HNRNPK leads to a mild form of Au-Kline syndrome. Clinical Genetics. doi:10.1111/cge.14763