GENE GUIDE

CHAMP1-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 CHAMP1-Related Syndrome.
a doctor sees a patient

CHAMP1-related syndrome is also called neurodevelopmental disorder with hypotonia, impaired language, and dysmorphic features, or mental retardation 40. For this webpage, we will be using the name CHAMP1-related syndrome to encompass the wide range of variants observed in the people identified.

CHAMP1-related syndrome happens when there are changes in the CHAMP1 gene. These changes can keep the gene from working as it should. 

Key Role

The CHAMP1 gene plays a key role in the growth of brain cells. 

Symptoms

Because the CHAMP1 gene is important for brain activity, many people who have CHAMP1-related syndrome have: 

  • Intellectual disability 
  • Speech impairments 
  • Small head, also called microcephaly 
  • Low muscle tone 
  • Gastroesophageal reflux disease (GERD) 
  • Feeding difficulties 
  • Features of autism 
  • Movement issues, such as ataxia (uncoordinated walking) 
  • Seizures 
  • Eye and vision issues 
  • Sleep issues

CHAMP1-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 CHAMP1 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 CHAMP1 plays a key role in development, de novo variants in this gene can have a meaningful effect.

Research shows that CHAMP1-related syndrome is often the result of a de novo variant in CHAMP1. Many parents who have had their genes tested do not have the CHAMP1 genetic variant found in their child who has the syndrome. In some cases, CHAMP1-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

CHAMP1-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in CHAMP1 they will likely have symptoms of CHAMP1-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 CHAMP1 gene?

No parent causes their child’s CHAMP1-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 CHAMP1-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 CHAMP1-related syndrome, the sibling’s risk of having a child who has CHAMP1-related syndrome depends on the sibling’s genes and their parents’ genes.

  • If neither parent has the same genetic variant causing CHAMP1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit CHAMP1-related syndrome.

As of 2024, over 53 people with CHAMP1-related syndrome have been identified in a medical clinic. 

People who have CHAMP1-related syndrome may look different. Appearance can vary and can include some but not all of these features: 

  • Open mouth 
  • Thin upper lip 
  • Low muscle tone in the face 
  • Longer than average face 
  • Pointed chin 
  • Low-set ears

Scientists and doctors have only just begun to study CHAMP1-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 CHAMP1-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.

Researchers think that genetic variants causing CHAMP1-related syndrome result in differing medical features, depending on the variant. People with truncating variants might have more severe medical features than people with a deletion that includes the CHAMP1 gene. The information below includes all people with a pathogenic or likely pathogenic variant that causes CHAMP1-related syndrome 

Speech and Learning 

People with CHAMP1-related syndrome had developmental or intellectual disability, and speech delay. 

  • 33 out of 33 people had developmental delay or intellectual disability (100 percent
  • 20 out of 20 people had speech issues (100 percent

Behavior 

Behavioral issues occurred in people with CHAMP1-related syndrome, including friendly behavior, autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), aggression, self-injury, and inappropriate laughter. 

  • 8 out of 10 people had friendly behavior (80 percent
  • 13 out of 40 people had autism spectrum disorder (33 percent)
  • 9 out of 40 people had ADHD (23 percent)
80%
8 out of 10 people had friendly behavior.
33%
13 out of 40 people had autism spectrum disorder.
23%
9 out of 40 people had ADHD.

Brain 

About 1 in 5 people with CHAMP1-related syndrome had seizures. People had a smaller than average head size (microcephaly) and brain changes observed on magnetic resonance imaging (MRI). Brain changes included developmental defects of the corpus callosum, decreased cerebellar size, and abnormal white matter (delayed myelination or under myelination). Some people had a larger than average head size (macrocephaly). 

  • 9 out of 44 people had seizures (21 percent)
  • 22 out of 45 people had microcephaly (49 percent)
  • 13 out of 35 people had brain changes on MRI (37 percent)
Human head showing brain outline
21%
9 out of 44 people had seizures.
49%
22 out of 45 people had microcephaly.
37%
13 out of 35 people had brain changes on MRI.

Mobility 

Most people with CHAMP1-related syndrome had lower than average muscle tone (hypotonia) and were able to walk independently over the age of 2 years old. A few people had spasticity. 

  • 24 out of 31 people had hypotonia (77 percent) 

Feeding and digestion  

People with CHAMP1-related syndrome had neonatal feeding difficulties and gastroesophageal reflux disease (GERD). 

  • 23 out of 42 people had neonatal feeding difficulties (55 percent)
  • 17 out of 42 people had GERD (41 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 CHAMP1-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.

  • Abi Raad, S., Yazbeck Karam, V., Chouery, E., Mehawej, C., & Megarbane, A. (2023). CHAMP1-related disorder: Sharing 20 years of thorough clinical follow-up and review of the literature. Genes (Basel), 14(8), 1546. https://pubmed.ncbi.nlm.nih.gov/37628598/
  • Levy, T., Pichardo, T., Silver, H., Lerman, B., Zweifach, J., Halpern, D., Siper, P. M., Kolevzon, A., & Buxbaum, J. D. (2023). Prospective phenotyping of CHAMP1 disorder indicates that coding mutations may not act through haploinsufficiency. Human Genetics, 142(9), 1385-1394. https://pubmed.ncbi.nlm.nih.gov/37454340/