GENE GUIDE

VAMP2-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 VAMP2-Related Syndrome.
a doctor sees a patient

VAMP2-related syndrome is also called neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements. For this webpage, we will be using the name VAMP2-related syndrome to encompass the wide range of variants observed in the people identified.

VAMP2-related syndrome happens when there are changes in the VAMP2 gene. These changes can keep the gene from working as it should.

Key Role

The VAMP2 gene plays a role in cell communication in the brain.

Symptoms

Because the VAMP2 gene is important in brain development and function, many people who have VAMP2-related syndrome have:

  • Developmental delay
  • Intellectual disability
  • Delayed speech or are non-verbal
  • Delayed sitting and walking
  • Shaky movement or walking
  • Autism

VAMP2-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 VAMP2 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 VAMP2 plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that VAMP2-related syndrome is often the result of a de novo variant in VAMP2. Many parents who have had their genes tested do not have the VAMP2 genetic variant found in their child who has the syndrome. In some cases, VAMP2-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 VAMP2 they will likely have symptoms of VAMP2-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 VAMP2 gene?

No parent causes their child’s VAMP2-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 VAMP2-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 VAMP2-related syndrome, the sibling’s risk of having a child who has VAMP2-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing VAMP2-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit VAMP2-related syndrome. 

As of 2024, at least 12 people with VAMP2-related syndrome have been identified in medical research.

People who have VAMP2-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Lower than average muscle tone
  • Smaller than average head size
  • Shorter than average height
  • Low-set ears
  • Pointed chin
  • Eyes that are not aligned
  • Open mouth

Scientists and doctors have only just begun to study VAMP2-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 VAMP2-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

All people with VAMP2-related syndrome had developmental delay and intellectual disability and speech difficulties that included speech delays, absent speech, or limited speech as they got older. Some people were able to do age-appropriate activities of daily living, such as getting themselves dressed, and some were entirely dependent on others for their needs even as they got older. This is based on information from people ages 3 to 39 years old.

  • 12 out of 12 people had developmental delay and intellectual disability (100 percent)
  • 11 out of 12 people had speech delays (92 percent)

Behavior

Some people with VAMP2-related syndrome had features of autism and other behavioral challenges. Behavioral issues included self-injurious behavior, hyperactivity, or aggressive outbursts. In addition, some had ‘Rett-like features’ with stereotypic movements that are associated with another genetic condition.

  • 9 out of 10 people had features of autism (90 percent)

Brain

About one-half of people with VAMP2-related syndrome had seizures. Various brain changes were observed on magnetic resonance imaging (MRI) in some people.

  • 6 out of 12 people had seizures (50 percent)
  • 4 out of 11 people had brain changes on MRI (37 percent)
Human head showing brain outline
50%
6 out of 12 people had seizures.
37%
4 out of 11 people had brain changes on MRI.

Mobility

Many people had low muscle tone, with or without a movement disorder. Movement issues included ataxia, tremor, unpredictable muscle movements, or stiffness.

  • 8 out of 12 people had low muscle tone (67 percent)
  • 6 out of 12 people had movement issues (50 percent)
67%
8 out of 12 people had low muscle tone.
50%
6 out of 12 people had movement issues.

Vision and hearing

Some people with VAMP2-related syndrome had central vision issues.

  • 4 out of 11 people had vision issues (36 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.”

Raging Raymond Foundation

Their mission is to spread awareness about rare genetic conditions impairing brain development and neurological development in children, advocate for the causes, drive research into the disorders, and seek therapeutic interventions.

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.

  • Bogue, D., Ryan, G., Wassmer, E., Genomics England Research Consortium, & Naik, S. (2023). VAMP2 gene-related neurodevelopmental disorder: A differential diagnosis for Rett/Angelman-type spectrum of disorders. Molecular Syndromology, 14(5), 449-456. https://pubmed.ncbi.nlm.nih.gov/37901860/

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