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CTCF-related syndrome is also called CTCF-related neurodevelopmental disorder and intellectual developmental disorder, autosomal dominant 21. For this webpage, we will be using the name CTCF-related syndrome to encompass the wide range of variants observed in the people identified.
What is CTCF-related syndrome?
CTCF-related syndrome happens when there are changes to the CTCF gene. These changes can keep the gene from working as it should.
Key Role
The CTCF gene plays a key role in the growth of the brain and the body. The CTCF gene helps to control other genes in the brain.
Symptoms
Because the CTCF gene is important in brain development and function, many people who have CTCF-related syndrome have:
- Global developmental delay
- Intellectual disability
- Speech delay
- Seizures
- Autism
- Behavioral issues like ADHD, anxiety, and aggression
- Vision issues
- Hearing loss
- Congenital heart defects
- Genitourinary issues
- Slow growth
- Small head size
- Feeding issues
- Gastrointestinal issues
- Sleep issues
- Recurrent infections
- Dental issues
- Cleft palate
- Low muscle tone
What causes CTCF-related syndrome?
CTCF-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 CTCF 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 CTCF plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that CTCF-related syndrome is often the result of a de novo variant in CTCF. Many parents who have had their genes tested do not have the CTCF genetic variant found in their child who has the syndrome. In some cases, CTCF-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
CTCF-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in CTCF they will likely have symptoms of CTCF-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 CTCF gene?
No parent causes their child’s CTCF-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 of future children will have CTCF-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 CTCF-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 CTCF-related syndrome, the sibling’s risk of having a child who has CTCF-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing CTCF-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit CTCF-related syndrome.
How many people have CTCF-related syndrome?
As of 2024, at least 102 people with CTCF-related syndrome have been described in medical research. The first case of CTCF-related syndrome was described in 2013.
Do people who have CTCF-related syndrome look different?
People who have CTCF-related syndrome may look different although features are non-specific. Appearance can vary and may include some but not all of these features:
- Widely spaced and/or deep-set eyes
- Broad nasal bridge
- Broad nasal tip
- Thin vermilion of the upper lip
How is CTCF-related syndrome treated?
Scientists and doctors have only just begun to study CTCF-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 CTCF-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 CTCF-related syndrome
Speech and Learning
Almost all people with CTCF-related syndrome had global developmental delay/intellectual disability delay, and many people had speech delay.
- 93 out of 102 people had global developmental delay or intellectual disability (91 percent)
- 66 out of 102 people had speech delay (65 percent)
Behavior
Some people with CTCF-related syndrome had autism and behavioral issues like aggression, anxiety, difficulty regulating emotions, destructive behaviors, oppositional behaviors, and self-injurious behaviors. Some people also had sleep issues.
- 32 out of 102 people had autism (31 percent)
- 53 out of 102 people had behavioral issues (52 percent)
- 35 out of 102 people had sleep issues (34 percent)
Brain
Some people with CTCF-related syndrome had seizures and a small head size. Almost one-half of people had low muscle tone, or microcephaly.
- 18 out of 102 people had seizures (18 percent)
- 27 out of 102 people had a small head size (26 percent)
- 46 out of 102 people had low muscle tone (45 percent)
Medical and physical concerns linked to CTCF-related syndrome
Growth and Gastrointestinal tract
People with CTCF-related syndrome had growth issues, a short stature, and gastrointestinal issues like constipation.
- 23 out of 102 people had a short stature (23 percent)
- 30 out of 102 people had low body weight (29 percent)
- 35 out of 102 people had gastrointestinal issues (34 percent)
Heart and Urogenital tract
About one-quarter of people with CTCF-related syndrome had heart issues, most commonly a hole in the heart, and urogenital issues like underdeveloped kidneys or they had one instead of two kidneys.
- 22 out of 102 people had heart issues (22 percent)
- 25 out of 102 people has urogenital issues (25 percent)
Hearing and vision
People with CTCF-related syndrome had hearing issues like bilateral hearing loss, and/or vision issues like crossed eyes.
- 24 out of 102 people had hearing issues (24 percent)
- 57 out of 102 people had vision issues (56 percent)
Dental
Some people with CTCF-related syndrome had dental issues like impacted or crowded teeth and tooth decay. Some people also had palatal defects like a cleft palate.
- 40 out of 102 people had tooth issues (39 percent)
- 26 out of 102 people had palatal issues (26 percent)
Where can I find support and resources?
CTCF Related Disorder Support Group Genetics for Families
www.facebook.com/groups/642805392875542
Simons Searchlight is another research program sponsored and run by the Simons Foundation Autism Research Initiative, also known as SFARI. As part of the next step in your research journey, Simons Searchlight offers you the opportunity to partner with scientists and other families who have the same gene change. Simons Searchlight is a registry for more than 200 genetic changes that are associated with neurodevelopmental conditions, including autism spectrum disorder. Simons Searchlight makes it easier for researchers to access the information they need to advance research on a condition. To register for Simons Searchlight, go to the Simons Searchlight website at www.simonssearchlight.org and click “Join Us Today”.
Learn more about Simons Searchlight
www.simonssearchlight.org/frequently-asked-questions
Simons Searchlight page on CTCF
www.simonssearchlight.org/research/what-we-study/ctcf
Simons Searchlight CTCF Facebook community
Sources and References
The content in this guide comes from published studies about CTCF-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.
- Gregor A. et al. American Journal of Human Genetics, 93, 124-131, (2013). De novo mutations in the genome organizer CTCF cause intellectual disability www.ncbi.nlm.nih.gov/pubmed/23746550
- Bastaki F. et al. BMC Medical Genetics, 18, 68, (2017). Identification of a novel CTCF mutation responsible for syndromic intellectual disability – A case report www.ncbi.nlm.nih.gov/pubmed/28619046
- Chen F. et al. American Journal of Medical Genetics Part C, Seminars in Medical Genetics, 181, 218-225, (2019). Three additional de novo CTCF mutations in Chinese patients help to define an emerging neurodevelopmental disorder www.ncbi.nlm.nih.gov/pubmed/30893510
- Konrad EDH. et al. Genetics in Medicine: Official Journal of the American College of Medical Genetics, (2019). CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum www.ncbi.nlm.nih.gov/pubmed/31239556
- Valverde de Morales, H. G., Wang, H. V., Garber, K., Cheng, X., Corces, V. G., & Li, H. (2023). Expansion of the genotypic and phenotypic spectrum of CTCF-related disorder guides clinical management: 43 new subjects and a comprehensive literature review. American Journal of Medical Genetics Part A, 191(3), 718-729. https://pubmed.ncbi.nlm.nih.gov/36454652/
- Valverde de Morales, H. G., Wang, H. L., Garber, K., Corces, V., & Li, H. CTCF-related disorder. 2024 Apr 25. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK603087/