CASZ1-Related Syndrome
What is CASZ1-related syndrome?
CASZ1-related syndrome happens when there are changes in the CASZ1 gene. These changes can keep the gene from working as it should.
Key Role
CASZ1 controls other genes that play a key role in brain, heart, and kidney development.
Symptoms
Because the CASZ1 gene is important for brain activity, many people who have CASZ1-related syndrome have:
- Developmental delay
- Intellectual disability
- Autism
- Heart defects
What causes CASZ1-related syndrome?
CASZ1-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 CASZ1 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 CASZ1 plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that CASZ1-related syndrome is often the result of a de novo variant in CASZ1. Many parents who have had their genes tested do not have the CASZ1 genetic variant found in their child who has the syndrome. In some cases, CASZ1-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
CASZ1-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in CASZ1 they will likely have symptoms of CASZ1-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 CASZ1 gene?
No parent causes their child’s CASZ1-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 CASZ1-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 CASZ1-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 CASZ1-related syndrome, the sibling’s risk of having a child who has CASZ1-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing CASZ1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit CASZ1-related syndrome.
How many people have CASZ1-related syndrome?
As of 2024, over 20 people with CASZ1-related syndrome have been identified in large-scale research studies. The first case of this condition was found in 2017.
Do people who have CASZ1-related syndrome look different?
We do not yet know if people who have de novo changes in the CASZ1 gene look different from others.
How is CASZ1-related syndrome treated?
Scientists and doctors have only just begun to study CASZ1-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 CASZ1-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 and the Simons Searchlight quarterly registry report. 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 CASZ1-related syndrome
Most people with CASZ1-related syndrome were identified from large-scale genetic sequencing studies. Usually, researchers do not have as many medical details on the participants in their studies. More research and participation in research is needed to be able to understand how people with CASZ1-related syndrome develop.
Some of the medical features reported for people with CASZ1-related syndrome were autism, intellectual disability, developmental disorder, and a disruption in the heart muscle (cardiomyopathy) or problems with the heart structure that was present at birth (congenital heart diseases).
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 CASZ1 – www.simonssearchlight.org/research/what-we-study/casz1
- Simons Searchlight CASZ1 Facebook community – https://www.facebook.com/groups/casz1
Sources and References
The content in this guide comes from published studies about CASZ1-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.
- Jian, H., & Poetsch, A. (2023). CASZ1: Current implications in cardiovascular diseases and cancers. Biomedicines, 11(7), 2079. https://pubmed.ncbi.nlm.nih.gov/37509718/
- Wang, T., Hoekzema, K., Vecchio, D., Wu, H., Sulovari, A., Coe, B. P., Gillentine, M. A., Wilfert, A. B., Perez-Jurado, L. A., … & Eichler, E. E. (2020). Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders. Nature Communications, 11(1), 4932. https://pubmed.ncbi.nlm.nih.gov/33004838/ [correction: https://pubmed.ncbi.nlm.nih.gov/33087701/]
- Zhou, X., Feliciano, P., Shu, C., Wang, T., Astrovskaya, I., Hall, J. B., Obiajulu, J. U., Wright, J. R., Murali, S. C., Xu, S. X., … & Chung, W. K. (2022). Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes. Nature Genetics, 54(9), 1305-1319. https://pubmed.ncbi.nlm.nih.gov/35982159/