GENE GUIDE

FBXO11-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 FBXO11-Related Syndrome.
a doctor sees a patient

FBXO11-related syndrome is also called intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (IDDFBA). For this webpage, we will be using the name FBXO11-related syndrome to encompass the wide range of variants observed in the people identified.

FBXO11-related syndrome happens when there are changes in the FBXO11 gene. These changes can keep the gene from working as it should.

Key Role

The FBXO11 gene plays a role in cell cycle control.

Symptoms

Because the FBXO11 gene is important in brain development and function, many people who have FBXO11-related syndrome have:

  • Developmental delay
  • Intellectual disability
  • Delayed speech and walking
  • Features of autism
  • Seizures
  • Smaller than average head size
  • Low muscle tone

FBXO11-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 FBXO11 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 FBXO11 plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that FBXO11-related syndrome is often the result of a de novo variant in FBXO11. Many parents who have had their genes tested do not have the FBXO11 genetic variant found in their child who has the syndrome. In some cases, FBXO11-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

FBXO11-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in FBXO11 they will likely have symptoms of FBXO11-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.

X-Linked Dominant Genetic Syndrome

Sex chromosomes
Non-carrier father
Non-carrier mother
Sex chromosomes
Genetic variant happens in X-chromosome in sperm or egg, or after fertilization
Non-carrier female
Female child with X-linked genetic condition
Male child with X-linked
genetic condition
Non-carrier
male

Why does my child have a change in the FBXO11 gene?

No parent causes their child’s FBXO11-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 FBXO11-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 FBXO11-related syndrome, the sibling’s risk of having a child who has FBXO11-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing FBXO11-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit FBXO11-related syndrome. 

As of 2024, at least 84 people with FBXO11-related syndrome have been identified in a medical clinic.

People who have FBXO11-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Smaller than average head size
  • Long face
  • Wide-set eyes
  • Eyes that do not align
  • Small mouth, ears, hands, and feet

Scientists and doctors have only just begun to study FBXO11-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 FBXO11-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.

Researchers have been investigating if there is a link between the type of FBXO11 variant and the physical features someone may have. Studies suggest that people with gene-disrupting variants are more likely to be overweight, whereas people with missense variants are more likely to have short height. Researchers need to study more people to investigate if there are other potential differences. The below information includes anyone with a genetic variant in FBXO11.

Speech and Learning

All people with FBXO11-related syndrome had developmental delay or intellectual disability.

  • 71 out of 71 people had developmental delay or intellectual disability (100 percent)

The severity varies among people:

  • 38 out of 71 people had mild intellectual disability (54 percent)
  • 23 out of 71 people had mild or moderate intellectual disability (32 percent)
  • 11 out of 71 people had severe intellectual disability (14 percent)
54%
38 out of 71 people had mild intellectual disability.
32%
23 out of 71 people had mild to moderate intellectual disability.
14%
11 out of 71 people had severe intellectual disability.

Behavior

Many people with FBXO11-related syndrome had behavioral findings, such as autism, attention-deficit/hyperactivity disorder (ADHD), or anxiety.

  • 48 out of 68 people had behavior issues (71 percent)

Brain

Some people with FBXO11-related syndrome had seizures or an abnormal electroencephalogram (EEG). More people had a smaller than average head size, also called microcephaly, than a larger than average head size, also called macrocephaly. Almost one-half of people had brain changes seen on magnetic resonance imaging (MRI).

  • 20 out of 69 people had seizures or abnormal EEG (29 percent)
  • 15 out of 68 people had microcephaly (22 percent)
  • 3 out of 68 people had macrocephaly (4 percent)
  • 22 out of 51 people had brain findings on MRI (43 percent)
Human head showing brain outline
29%
20 out of 69 people had seizures or abnormal EEG.
22%
15 out of 68 people had microcephaly.
4%
3 out of 68 people had macrocephaly.
43%
22 out of 51 people had brain findings on MRI.

Physical findings

Many people had low muscle tone and some were overweight or had overeating, or had a shorter than average height.

  • 43 out of 63 people had low muscle tone (68 percent)
  • 23 out of 71 people were overweight or had overeating (32 percent)
  • 14 out of 69 people were shorter than average (20 percent)
68%
43 out of 63 people had low muscle tone.
32%
23 out of 71 people were overweight or had overeating.
20%
14 out of 69 people were shorter than average.

Vision 

Almost one-half of people with FBXO11-related syndrome had vision issues.

  • 32 out of 66 people had vision issues (48 percent)

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

The content in this guide comes from published studies about FBXO11-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., Meerbrei, T., Gerstner, T., Toutain, A., Lynch, S. A., Stals, K., Maxton, C., Lemke, J. R., Bernat, J. A., … Zweier, C. (2022). De novo missense variants in FBXO11 alter its protein expression and subcellular localization. Human Molecular Genetics, 31(3), 440-454. https://pubmed.ncbi.nlm.nih.gov/34505148/

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