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 is also called Intellectual developmental disorder, autosomal dominant 52. For this webpage, we will be using the name ASH1L-related syndrome to encompass the wide range of variants observed in the people identified.

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 brain development and function, many people who have ASH1L-related syndrome have:

  • Speech delay
  • Developmental delay
  • Intellectual disability
  • Learning difficulties
  • Poor or absent speech
  • Seizures 
  • Sleeping issues
  • Autism
  • Behavioral issues
  • Anxiety 
  • Lower than average muscle tone

ASH1L-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 ASH1L 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 ASH1L plays a key role in development, de novo variants in this gene can have a meaningful effect. 

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

Autosomal dominant conditions

ASH1L-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in ASH1L they will likely have symptoms of ASH1L-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 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 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 ASH1L-related syndrome, the sibling’s risk of having a child who has ASH1L-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing ASH1L-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit ASH1L-related syndrome. 

As of 2024, at least 61 people with ASH1L-related syndrome have been identified in a medical clinic. The first case of ASH1L-related syndrome was described in 2012.

People who have ASH1L-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Lower than average muscle tone
  • Some people have been described to have unique facial features, but there is no common pattern

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.

Speech and Learning

Most people with ASH1L-related syndrome had developmental delay or intellectual disability and speech delays.

  • 17 out of 19 people had developmental delay or intellectual disability (90 percent)
  • 8 out of 12 had speech delays (67 percent)

Behavior

Many people with ASH1L-related syndrome had attention-deficit/hyperactivity disorder (ADHD), autism, and obsessive behaviors.

  • 9 out of 10 people had ADHD (90 percent)
  • 9 out of 13 people had autism (69 percent)
  • 6 out of 7 people had obsessive behaviors (86 percent)
90%
9 out of 10 people had ADHD.
69%
9 out of 13 people had autism.
86%
6 out of 7 people had obsessive behaviors.

Brain

About half of people with ASH1L-related syndrome had seizures, and sleep disorders.

  • 8 out of 14 people had seizures (57 percent)
  • 7 out of 12 people had sleep disorders (58 percent)
Human head showing brain outline

Mobility

Many people had movement issues, such as motor delays; low muscle tone, also called hypotonia; and issues with walking. Walking issues included an inability to control distance, speed, and range of motion, or movement without coordination.

  • 7 out of 14 people had motor delays (50 percent)
  • 5 out of 11 people had hypotonia (46 percent)
  • 4 out of 7 people had walking issues (57 percent)
50%
7 out of 14 people had motor delays.
46%
5 out of 11 people had hypotonia.
57%
4 out of 7 people had walking issues.

Physical findings

People with ASH1L-related syndrome sometimes had bone formation issues. Physical findings included facial changes; a sideways curve of the spine, also called scoliosis; and ribs and sternum growth inwards or outwards.

  • 9 out of 13 people had facial findings (69 percent)
  • 2 out of 9 people had scoliosis (22 percent)
  • 2 out of 9 people had ribs and sternum growth issues (22 percent)

Other features

Some people had vision issues. Vision issues included but were not limited to hyperopia (farsightedness), strabismus (crossed eyes), astigmatism (an imperfection of the eye that causes blurred distance and near vision), and nystagmus (repetitive uncontrolled eye movement). Some people had feeding issues or hearing impairment.

  • 7 out of 13 people had vision issues (54 percent)
  • 5 out of 10 people had feeding issues (50 percent)
  • 4 out of 11 people had hearing impairment (36 percent)

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.”

Sources and References

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
  • Cordova, I., Blesson, A., Savatt, J. M., Sveden, A., Mahida, S., Hazlett, H., Rooney Riggs, E., Chopra, M., & Brain Gene Registry Subset of the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel (2024). Expansion of the Genotypic and Phenotypic Spectrum of ASH1L-Related Syndromic Neurodevelopmental Disorder. Genes, 15(4), 423. https://pubmed.ncbi.nlm.nih.gov/38674358/

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