GENE GUIDE

ASH1L-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 ASH1L-Related Syndrome.
a doctor sees a patient

ASH1L-related syndrome happens when there are changes to the ASH1L gene. These changes can keep the gene from working as it should.

Key Role

The ASH1L gene plays a key role in brain development. It controls the activity of other genes.

Symptoms

ASH1L-related syndrome can have mild to severe effects on the development of communication, social, and learning skills. Because the ASH1L gene is important in the development of brain cells, many people who have ASH1L-related syndrome have:

  • Speech delay
  • Intellectual disability
  • Learning difficulties

Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the ASH1L 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.

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 ASH1L plays an important role in development, de novo changes in this gene can have a meaningful effect.

Research shows that ASH1L-related syndrome is often the result of a de novo change in ASH1L. Many parents who have had their genes tested do not carry the gene change found in their child who has the syndrome. In some cases, ASH1L-related syndrome happens because the gene change was passed down from a parent. This is called dominant inheritance.

Dominant Inheritance

Children have a 50% chance of inheriting the genetic change.

Child who has genetic change in ASH1L gene

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

Why does my child have a change in the ASH1L gene?

No parent causes their child’s ASH1L-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 ASH1L-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 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 change in the gene.
  • If one birth parent has the same gene change found in their child, the chance of having another child who has the syndrome is 50 percent.

For a symptom-free sibling, a brother or sister, of someone who has ASH1L-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 ASH1L-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 ASH1L-related syndrome is 50 percent.

For a person who has ASH1L-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2019, about 20 people in the world with changes in the ASH1L gene had been described in the medical literature. The first case of ASH1L-related syndrome was described in 2012. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

People who have ASH1L-related syndrome generally do not look very different from others.

Scientists and doctors have only just begun to study ASH1L-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 ASH1L-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.

Behavior

Most people who had ASH1L-related syndrome had behavioral issues. These may include autism, attention deficit hyperactivity disorder, also called ADHD, and obsessive behaviors. About one-quarter of people had sleep problems, including excessive daytime sleepiness and sleep apnea, a disorder in which breathing stops and starts during sleep.

  • 11 out of 13 people had behavioral issues, including autism, ADHD, and obsessive behaviors.

Speech

More than one-third of people who had the condition had speech delays, which vary in severity.

  • 5 out of 13 people had a speech delay.

Learning

Everyone had some level of intellectual disability, ranging from mild to severe.

  • 13 out of 13 people had an intellectual disability.
85%
11 out of 13 people had behavioral issues, including autism, ADHD, and obsessive behaviors.
38%
5 out of 13 people had a speech delay.
100%
13 out of 13 people had an intellectual disability.

Brain

  • Nearly one-quarter of people who had ASH1L-related syndrome had seizures.

Birth defects

Some people had birth defects, including increased distance between the eyes and failure of the testes to descend.

Motor concerns

  • 4 out of 13 people had motor delays.

Feeding and digestion issues

  • 4 out of 13 people had gastrointestinal issues, including constipation.
31%
4 out of 13 people had motor delays. 
31%
4 out of 13 people had gastrointestinal issues, including constipation.

Where can I find support and resources?

Care4ASH1L

Their mission is to advance research on ASH1L to help find novel therapeutic interventions in order to ameliorate the lives of those affected by ASH1L mutation. They aim to raise funds to facilitate and leverage research with the purpose of having clinical trials.

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.”

The content in this guide comes from published studies about ASH1L-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.

  • Shen W. et al. European Journal of Medical Genetics, 62, 55-60, (2019). De novo loss-of- function variants of ASH1L are associated with an emergent neurodevelopmental disorder, www.ncbi.nlm.nih.gov/pubmed/29753921
  • Okamoto N. et al. American Journal of Medical Genetics, Part A, 173, 1644-1648, (2017). Novel MCA/ID syndrome with ASH1L mutation www.ncbi.nlm.nih.gov/pubmed/28394464

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