GENE GUIDE

GIGYF1-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 GIGYF1-Related Syndrome.
a doctor sees a patient

GIGYF1-related syndrome happens when there are changes in the GIGYF1 gene. These changes can keep the gene from working as it should.

Key Role

We can tell you that GIGYF1 plays an important role in brain development and is associated with autism. The gene is also likely associated with language and learning.

Symptoms

Because the GIGYF1 gene is important in brain development and function, people who have GIGYF1-related syndrome have:

  • Autism
  • Intellectual disability
  • Speech delay

What is my genetic result?

You are receiving this information because you or your child has a gene change in a newly discovered autism gene, GIGYF1.

Your or your child’s gene change is ‘de novo’, or new. That is, it was not inherited from a parent.

Because GIGYF1 is so new in autism, we don’t have specific information on what medical issues you might expect now and in the near future. We can tell you that GIGYF1 plays an important role in brain development and is associated with autism. The gene is also likely associated with language and learning.

You, or your family member, are one of what may be a very small number of people in the world with autism who have a gene change in GIGYF1. Scientists expect to find more people who have changes in GIGYF1 as access to genetic testing improves.

GIGYF1-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 GIGYF1 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 GIGYF1 plays a key role in development, de novo variants in this gene can have a meaningful effect.

Research shows that GIGYF1-related syndrome is often the result of a de novo variant in GIGYF1. Many parents who have had their genes tested do not have the GIGYF1 genetic variant found in their child who has the syndrome. In some cases, GIGYF1-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

GIGYF1-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in GIGYF1 they will likely have symptoms of GIGYF1-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 GIGYF1 gene?

No parent causes their child’s de novo gene change. 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 GIGYF1-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 GIGYF1-related syndrome, the sibling’s risk of having a child who has GIGYF1-related syndrome depends on the sibling’s genes and their parents’ genes.

  • If neither parent has the same genetic variant causing GIGYF1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit GIGYF1-related syndrome.

As of 2024, at least 67 people with GIGYF1-related syndrome have been identified in medical research. The first case of this condition was described in 2014.

People who have GIGYF1-related syndrome might not look very different.

Scientists and doctors have only just begun to study people who have changes in the GIGYF1 gene. At this point, there are no medicines designed to treat the condition. 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
  • Developmental 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 people who have autism 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.

A doctor may also refer people to other specialists as needed.

Some GIGYF1 variants were inherited from a parent. Some of these parents had developmental delays, anxiety, ADHD, and depression. The information below summarizes research on the child or dependent identified with a GIGYF1 variant.

Speech and Learning

Some people with GIGYF1-related syndrome had speech delay, intellectual disability, or learning disability. Learning disabilities included issues with reading, writing, math, or a nonverbal learning disability.

  • 37 out of 60 people had speech delay (62 percent)
  • 14 out of 60 people had intellectual disability (23 percent)
  • 13 out of 49 people had a learning disability (27 percent)
62%
37 out of 60 people had speech delay.
23%
14 out of 60 people had intellectual disability.
27%
13 out of 49 people had a learning disability.

Behavior

Autism was the most common feature of GIGYF1-related syndrome. Some people had attention-deficit/hyperactivity disorder (ADHD) or anxiety.

  • 53 out of 58 people had autism or features of autism (91 percent)
  • 19 out of 56 people had ADHD (34 percent)
  • 12 out of 56 people had anxiety (21 percent)
91%
53 out of 58 people had autism or features of autism.
34%
19 out of 56 people had ADHD.
21%
12 out of 56 people had anxiety.

Brain

Seizures were not reported in people with GIGYF1-related syndrome, but some people had an abnormal electroencephalogram (EEG) or brain changes seen on magnetic resonance imaging (MRI).

  • 3 out of 5 people had an abnormal EEG (60 percent)
  • 2 out of 6 people had brain findings on MRI (33 percent)
Human head showing brain outline

Mobility

Some people who had GIGYF1-related syndrome were late in developing skills, such as sitting and walking.

  • 19 out of 60 people had motor delays (32 percent)

Other reported issues

Other issues included sleep issues, eating problems, and bowel accidents beyond expected age.

  • 18 out of 58 people had sleep issues (31 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 information in this guide comes from published studies about people who have autism who have de novo gene changes in GIGYF1. Below you can find details about each study, as well as links to summaries, or in some cases the full article.

  • Iossifov I. et al. Nature, 515, 216-221, (2014). The contribution of de novo coding mutations to autism spectrum disorder
    www.ncbi.nlm.nih.gov/pubmed/25363768
  • Krumm N. et al. Nature Genetics, 47, 582-588, (2015). Excess of rare, inherited truncating mutations in autism www.ncbi.nlm.nih.gov/pubmed/25961944
  • Chen, G., Yu, B., Tan, S., Tan, J., Jia, X., Zhang, Q., Zhang, X., Jiang, Q., Hua, Y., … & Guo, H. (2022). GIGYF1 disruption associates with autism and impaired IGF-1R signaling. The Journal of Clinical Investigation, 132(19), e159806. https://pubmed.ncbi.nlm.nih.gov/35917186/

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