GENE GUIDE

ASXL3-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 ASXL3-Related Syndrome.
a doctor sees a patient

ASXL3-related syndrome is also called Bainbridge-Ropers syndrome or BRPS. For this webpage, we will be using the name ASXL3-related syndrome to encompass the wide range of variants observed in the people identified.

ASXL3-related syndrome happens when there are changes to the ASXL3 gene. These changes can keep the gene from working as it should.

Key Role

The ASXL3 gene plays a key role in development of the brain and the body. It affects parts of the body including the spinal cord, liver, kidneys, and bone marrow.

Symptoms

Because the ASXL3 gene is important in the development and function of brain cells, many people who have ASXL3-related syndrome have:

  • Intellectual disability
  • Changes in skull facial features
  • Feeding problems
  • Delayed growth
  • Skeletal issues like scoliosis and marfanoid habitus
  • Autism or features of autism
  • Low muscle tone
  • Seizures
  • Vision issues

Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the ASXL3 gene: one copy from their mother, from the egg, and one copy from their father, from the sperm. In most cases, parents pass on exact copies of the gene to their child. But the process of copying genes is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both. Sometimes a random change happens in the sperm or egg. This change to the genetic code is called a ‘de novo’, or new, change. The child can be the first in the family to have the gene change.

Child who has genetic change in ASXL3 gene

Genetic change occurs in egg or sperm after fertilization
Child with de novo genetic change in autism gene

De novo changes can take place in any gene. We all have some de novo changes, most of which don’t affect our health. But because ASXL3 plays a key role in development, de novo changes in this gene can have a meaningful effect. Research shows that ASXL3-related syndrome is often the result of a de novo change in ASXL3. Many parents who have had their genes tested do not have the ASXL3 gene change found in their child who has the syndrome. In some cases, ASXL3-related syndrome happens because the gene change was passed down from a parent.

Why does my child have a change in the ASXL3 gene?

No parent causes their child’s ASXL3-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 ASXL3-related syndrome depends on the genes of both birth parents.

  • If neither birth parent has the same gene change found in their child, the chance of having another child with 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 change in the gene.
  • If one birth parent has the same gene change found in their child, the chance of having another child with the syndrome is 50 percent.

For a symptom-free sibling, a brother or sister, of someone who has ASXL3-related syndrome, the risk of having a child who has the syndrome depends on the symptom-free sibling’s genes and their parents’ genes.

  • If neither parent has the same gene change found in their child who has the syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who has ASXL3-related syndrome.
  • If one birth parent has the same gene change found in their child who has the syndrome, the symptom-free sibling has a small chance of also having the same gene change. If the symptom-free sibling has the same gene change as their sibling who has the syndrome, the symptom-free sibling’s chance of having a child who has ASXL3-related syndrome is 50 percent.

For a person who has ASXL3-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, at least 189 people with ASXL3-related syndrome have been identified in a medical clinic. The first case of ASXL3-related syndrome was described in 2013.

People who have ASXL3-related syndrome often have different facial features. Appearance can vary and can include some but not all of these features:

  • Wide mouth with full lower lip. High-arched roof of the mouth and crowded teeth.
  • Eyes that are slanted down. Eyes that are slanted up are less common.
  • Long nose with wide nasal bridge. Tip of nose is broad and pointed up.
  • Narrow head shape with wide forehead.
  • High-arched eyebrows.

Scientists and doctors have only just begun to study ASXL3-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 ASXL3-related syndrome should begin as early as possible, ideally before a child begins school. Surgery may be necessary for people who have issues with the roof of their mouth or severe curved spine. 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 studies. It highlights how many people have different symptoms. To learn more about the articles, see the Sources and references section of this guide.

Behavior

Most people who have ASXL3-related syndrome are on the autism spectrum. Many have sleep problems. Some flap their hands, rock, or breath rapidly, also known as hyperventilation. These actions are more common when a person is anxious. Self-injurious behavior like self biting, scratching and headbanging are common.

  • 78 percent of people with ASXL3-related syndrome are on the autism spectrum.

Speech

Many people who have ASXL3-related syndrome do not speak, and all have some speech delay.

  • 100 percent of people have speech delays.
78%
Are on the autism spectrum.
100%
Have a speech delay.

Learning

Everyone who has ASXL3-related syndrome has some level of intellectual disability. It can range from moderate to severe, but most cases are severe. These people often require special educational support.

The majority of people have intellectual disability, ranging from moderate to severe.

  • 98 percent have moderate to severe intellectual disability.

Some people who have ASXL3-related syndrome have seizures. These can be of different types, including absence — seizures with a lapse of awareness and blank staring spells; focal — seizures that initially affect only half the brain; and generalized tonic-clonic — seizures that involve the entire body. Seizures start very early in some people. For others, seizures can start later in life. Most people have normal brain magnetic resonance imaging (MRI).

  • 38 percent of people have seizures.

Mental health

People who have the syndrome may feel agitation or frustration for brief periods.

Growth

Height can vary. Some people are short, while others are tall and slender. Some people have spine issues, such as a curved spine, also called scoliosis. The majority of people have skeletal findings. Some skeletal findings include features resembling Marfan syndrome like a concave chest, flat feet, hypermobile joints, defects in the development of fingers, and delayed bone age. Also, low muscle tone is common.

  • 74 percent of people have skeletal findings.
  • 86 percent of people have low muscle tone.
78%
Have skeletal findings.
86%
Have low muscle tone.

People with ASXL3-related syndrome have facial features that develop differently than average.

  • 98 percent have facial features that develop differently.

Sitting and walking

Children who have ASXL3-related syndrome are often late in walking. Some never walk. 

Children who have the syndrome often meet motor milestones late. They may have trouble with movement of smaller muscles, such as fingers and hands, also called fine motor skills.

Feeding and Digestion issues

People who have the syndrome often have feeding issues, especially during early life and are diagnosed with failure to thrive. Some need a feeding tube.

  • 78 percent have feeding issues.

Eyes and eyesight

Some people have a lazy eye or trouble moving their eyes. The most common eye finding is crossed eyes.

  • About 50 percent of people have a lazy eye or trouble moving their eyes.

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 ASXL3-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.

  • Bainbridge MN. et al. Genome Medicine, 5, 11, (2013). De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome www.ncbi.nlm.nih.gov/pubmed/23383720
  • Balasubramanian M. et al. Journal of Medical Genetics, 54, 537-543, (2017). Delineating the phenotypic spectrum of Bainbridge-Ropers syndrome: 12 new patients with de novo, heterozygous, loss-of-function mutations in ASXL3 and review of published literature www.ncbi.nlm.nih.gov/pubmed/28100473
  • Myers KA. et al. Epilepsy Research, 140, 166-170, (2018). Childhood-onset generalized epilepsy in Bainbridge-Ropers syndrome www.ncbi.nlm.nih.gov/pubmed/29367179
  • Verhoeven W. et al. Neuropsychiatric Disease and Treatment, 14, 867-870, (2018). Phenotypic characterization of an older adult male with late-onset epilepsy and a novel mutation in ASXL3 shows overlap with the associated Bainbridge-Ropers syndrome www.ncbi.nlm.nih.gov/pmc/articles/PMC5877499
  • Schirwani, et al. (2021). Expanding the phenotype of ASXL3-related syndrome: A comprehensive description of 45 unpublished individuals with inherited and de novo pathogenic variants in ASXL3. American Journal of Medical Genetics part A. https://pubmed.ncbi.nlm.nih.gov/34436830/

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