GENE GUIDE

RERE-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 in 2025. 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 RERE-Related Syndrome.
a doctor sees a patient

RERE-related syndrome is also called neurodevelopmental disorder with or without anomalies of the brain, eye, or heart. For this webpage, we will be using the name RERE-related syndrome to encompass the wide range of variants observed in the people identified.

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

Key Role

The RERE gene plays a key role in the development of the brain, heart, and eyes.

Symptoms

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

  • Developmental delay, or intellectual disability, or both
  • Autism spectrum disorder or features of autism
  • Low muscle tone, also called hypotonia
  • Seizures
  • Changes in the structure of the heart
  • Behavioral issues, including attention-deficit/hyperactivity disorder (ADHD) and self-injurious behavior
  • Feeding issues
  • Vision/eye issues
  • Hearing loss
  • Genitourinary defects
  • Gastrointestinal issues
  • Brain changes observed on magnetic resonance imaging (MRI)

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

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

Autosomal dominant conditions

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

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

  • If neither parent has the same genetic variant causing RERE-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit RERE-related syndrome. 
  • If one biological parent has the same genetic variant causing RERE-related syndrome, the symptom-free sibling has a 50 percent chance of also having the same genetic variant. If the symptom-free sibling has the same genetic variant, their chance of having a child who has the genetic variant is 50 percent. 

For a person who has RERE-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, over 60 people with RERE-related syndrome have been described in medical research.

About 70 percent of people who have RERE-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Noticeable forehead
  • Low-set ears that are rotated backwards
  • Upward tilting nostrils
  • Broad eyebrows
  • Skin folds at the eyes, also called epicanthal folds

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

Learning

Many people with RERE-related syndrome had global developmental delay and/or intellectual disabilities, from mild to profound.

  • 19 out of 23 people had global developmental delay and/or intellectual disability (83 percent)

Behavior

People with RERE-related syndrome had behavioral issues, such as attention-deficit/hyperactivity disorder (ADHD), self-injurious behavior, and autism spectrum disorder.

  • 8 out of 23 people had autism spectrum disorder (35 percent)

Brain

Some people with RERE-related syndrome had low muscle tone (hypotonia), changes seen on magnetic resonance imaging (MRI), seizures, or a smaller than average head size (microcephaly).

  • 9 out of 23 people had hypotonia (39 percent)
  • 11 out of 23 people had changes seen on MRI (48 percent)
  • 2 out of 19 people had seizures (11 percent)
Human head showing brain outline
39%
9 out of 23 people had hypotonia.
48%
11 out of 23 people had changes seen on MRI.
11%
2 out of 19 people had seizures.

Vision and hearing

Some people with RERE-related syndrome had vision and hearing issues like crossed eyes (strabismus), nearsightedness (myopia), farsightedness (hyperopia), droopy eyelids (ptosis), and hearing loss.

  • 6 out of 23 people had vision issues (26 percent)
  • 6 out of 23 people had hearing issues (26 percent)

Gastrointestinal and genitourinary

People with RERE-related syndrome had gastrointestinal issues like reflux, pyloric hypertrophy, and duodenal atresia. Some people with RERE-related syndrome had genitourinary issues like urinary reflux.

  • 5 out of 23 people had gastrointestinal issues (22 percent)
  • 6 out of 23 people had genitourinary issues (26 percent)

Heart

Some people with RERE-related syndrome had heart issues, mainly a hole in the heart.

  • 11 out of 23 people had heart issues (48 percent)

Musculoskeletal

Some people with RERE-related syndrome had musculoskeletal issues like sideways curve of the spine (scoliosis), hip dysplasia, short height, cleft lip/palate, or choanal atresia.

  • 9 out of 23 people had musculoskeletal issues (39 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 RERE-related syndrome.

  • Fregeau, B., Kim, B. J., Hernández-García, A., Jordan, V. K., Cho, M. T., Schnur, R. E., Monaghan, K. G., Juusola, J., Rosenfeld, J. A., … & Sherr, E. H. (2016). De novo mutations of RERE cause a genetic syndrome with features that overlap those associated with proximal 1p36 deletions. American Journal of Human Genetics, 98(5), 963-970. https://pubmed.ncbi.nlm.nih.gov/27087320/
  • Jordan, V. K., Fregeau, B., Ge, X., Giordano, J., Wapner, R. J., Balci, T. B., Carter, M. T., Bernat, J. A., Moccia, A. N., … & Scott, D. A. (2018). Genotype-phenotype correlations in individuals with pathogenic RERE variants. Human Mutation, 39(5), 666-675. https://pubmed.ncbi.nlm.nih.gov/29330883/
  • Niehaus, A. D., Kim, J., & Manning, M. A. (2022). Phenotypic variability in RERE-related disorders and the first report of an inherited variant. American Journal of Medical Genetics Part A, 188(11), 3358-3363. https://pubmed.ncbi.nlm.nih.gov/36053530/
  • Li, Q., Li, W., Hu, K., Wang, Y., Li, Y., & Xu, J. (2024). A de novo variant in RERE causes autistic behavior by disrupting related genes and signaling pathway. Clinical Genetics, 105(3), 273-282. https://pubmed.ncbi.nlm.nih.gov/38018232/

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