GENE GUIDE

CSDE1-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 on 2024. 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 CSDE1-Related Syndrome.
a doctor sees a patient

CSDE1-related syndrome happens when there are changes in the CSDE1 gene. These changes can keep the gene from working as it should.

Key Role

The CSDE1 gene controls the activity of other genes that are important for brain growth.

Symptoms

Because the CSDE1 gene is important in brain development and function, many people who have CSDE1-related syndrome have:

  • Autism
  • Intellectual disability
  • Language and motor delay
  • Seizures
  • Large brain
  • Eye defects

CSDE1-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 CSDE1 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 CSDE1 plays a key role in development, de novo variants in this gene can have a meaningful effect.

Research shows that CSDE1-related syndrome is often the result of a de novo variant in CSDE1. Many parents who have had their genes tested do not have the CSDE1 genetic variant found in their child who has the syndrome. In some cases, CSDE1-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

CSDE1-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in CSDE1 they will likely have symptoms of CSDE1-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 CSDE1 gene?

No parent causes their child’s CSDE1-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 CSDE1-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 CSDE1-related syndrome, the sibling’s risk of having a child who has CSDE1-related syndrome depends on the sibling’s genes and their parents’ genes.

  • If neither parent has the same genetic variant causing CSDE1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit CSDE1-related syndrome.

As of 2024, at least 25 people with CSDE1-related syndrome have been identified in medical research. The first case of CSDE1-related syndrome was described in 2019.

People who have CSDE1-related syndrome might not look very different.

Scientists and doctors have only just begun to study CSDE1-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 CSDE1-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: 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.

Some CSDE1 variants were inherited from the parents. It is unclear if those parents had developmental issues because the researchers were unable to assess them for symptoms.

Speech and Learning

Most people with CSDE1-related syndrome had speech delay and intellectual disability.

  • 18 out of 19 people had speech delay (95 percent)
  • 15 out of 18people had intellectual disability (83 percent)

Behavior

Many people with CSDE1-related syndrome had behavioral issues, such as autism or features of autism, obsessive compulsive behavior, attention-deficit/hyperactivity disorder (ADHD), anxiety, or self-injurious behavior.

  • 17 out of 23 people had autism or features of autism (74 percent)
  • 4 out of 15 people had obsessive compulsive behavior (27 percent)
  • 9 out of 15 people had ADHD (60 percent)
  • 9 out of 15 people had anxiety (60 percent)
  • 3 out of 14 people had self-injurious behavior (21 percent)
74%
17 out of 23 people had autism or features of autism.
27%
4 out of 15 people had obsessive compulsive behavior.
60%
9 out of 15 people had ADHD.
60%
9 out of 15 people had anxiety.
21%
3 out of 14 people had self-injurious behavior.

Brain

Some people with CSDE1-related syndrome had seizures or an abnormal electroencephalogram (EEG). Almost one-half of people had brain changes seen on magnetic resonance imaging (MRI).

  • 7 out of 18 people had seizures (39 percent)
  • 6 out of 14 people had an abnormal EEG (43 percent)
  • 7 out of 16 people had brain findings on MRI (44 percent)
Human head showing brain outline
39%
7 out of 18 people had seizures.
43%
6 out of 14 people had an abnormal EEG.
44%
7 out of 16 people had brain findings on MRI.

Mobility

People who have CSDE1-related syndrome were usually late in developing skills, such as sitting and walking. About one-half of people had low muscle tone. Some people had muscle weakness and an intolerance to exercise.

  • 16 out of 19 people had motor delays (84 percent)
  • 7 out of 15 people had lower than average muscle tone (47 percent)

Growth and development

Some people were shorter than average in height and had defects of the hands and eyes. Eye issues included blurry vision of far objects, cataracts, or iris coloboma.

  • 3 out of 17 people had shorter than average height (18 percent)
  • 6 out of 17 people had defects of the hands (35 percent)
  • 8 out of 15 people had defects of the eyes (53 percent)
18%
3 out of 17 people had shorter than average height.
35%
6 out of 17 people had defects of the hands.
53%
8 out of 15 people had defects of the eyes.

Other medical findings

About one-half of people with CSDE1-related syndrome had recurrent infections and some had sleep issues.

  • 6 out of 14 people had recurrent infections (43 percent)
  • 4 out of 15 people had sleep issues (27 percent)

Adults

There have been very few adults described in the research publications—only two adults have been studied. One 44-year old with no intellectual disability and living independently developed psychiatric symptoms that were managed with medication. Another adult was 19 years old and developed schizophrenia. To date, very few people with CSDE1-related syndrome have been studied, and more adults need to participate in research to better understand the spectrum of medical symptoms people may develop.

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.”

Sources and References

  • Gangfuß, A., Lochmüller, H., Töpf, A., O’Heir, E., Horvath, R., Kölbel, H., Schweiger, B., Schara-Schmidt, U., & Roos, A. (2022). A de novo CSDE1 variant causing neurodevelopmental delay, intellectual disability, neurologic and psychiatric symptoms in a child of consanguineous parents. American Journal of Medical Genetics Part A, 188(1), 283-291. https://pubmed.ncbi.nlm.nih.gov/34519148/
  • Guo, H., Li, Y., Shen, L., Wang, T., Jia, X., Liu, L., Xu, T., Ou, M., Hoekzema, K., … & Xia, K. (2019). Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission. Science Advances, 5(9), eaax2166. https://pubmed.ncbi.nlm.nih.gov/31579823/
  • Krenn, M., Kepa, S., Kasprian, G., Riedhammer, K. M., Wagner, M., Goedl-Fleischhacker, U., & Milenkovic, I. (2022). A de novo truncating variant in CSDE1 in an adult-onset neuropsychiatric phenotype without intellectual disability. European Journal of Medical Genetics, 65(3), 104423. https://pubmed.ncbi.nlm.nih.gov/35026469/
  • Zhou, X., Feliciano, P., Shu, C., Wang, T., Astrovskaya, I., Hall, J. B., Obiajulu, J. U., Wright, J. R., Murali, S. C., … & 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/

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