GENE GUIDE

HIVEP2-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 HIVEP2-Related Syndrome.
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HIVEP2-related syndrome is also called intellectual developmental disorder, autosomal dominant 43. For this webpage, we will be using the name HIVEP2-related syndrome to encompass the wide range of variants observed in the people identified.

HIVEP2-related syndrome happens when there are changes to the HIVEP2 gene. These changes can keep the gene from working as it should.

Key Role

The HIVEP2 gene plays a key role in the growth of the brain.

Symptoms

Because the HIVEP2 gene is important for brain activity, many people who have HIVEP2-related syndrome have:

  • Intellectual disability
  • Global developmental delay
  • Behavior issues
  • Lower than average muscle tone
  • Poor or absent speech
  • Seizures
  • Anxiety
  • Brain changes seen on magnetic resonance imaging (MRI)
  • Poor feeding

HIVEP2-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 HIVEP2 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 HIVEP2 plays a key role in development, de novo variants in this gene can have a meaningful effect.

Research shows that HIVEP2-related syndrome is often the result of a de novo variant in HIVEP2. Many parents who have had their genes tested do not have the HIVEP2 genetic variant found in their child who has the syndrome. In some cases, HIVEP2-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

HIVEP2-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in HIVEP2 they will likely have symptoms of HIVEP2-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 HIVEP2 gene?

No parent causes their child’s HIVEP2-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 HIVEP2-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 HIVEP2-related syndrome, the sibling’s risk of having a child who has HIVEP2-related syndrome depends on the sibling’s genes and their parents’ genes.

  • If neither parent has the same genetic variant causing HIVEP2-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit HIVEP2-related syndrome.

As of 2024, at least 58 people with HIVEP2-related syndrome have been identified in a medical clinic. The first case of HIVEP2-related syndrome was described in 2015.

People who have HIVEP2-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Lower or higher than average muscle tone
  • Smaller than average head size
  • Wide-set eyes
  • Smaller than average mouth

Scientists and doctors have only just begun to study HIVEP2-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 HIVEP2-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 a major published article. It highlights how many people have different symptoms. To learn more about the article, see the Sources and references section of this guide.

Speech and Learning

All people with HIVEP2-related syndrome had developmental delay or intellectual disability, and many had language delays or impairment.

  • 27 out of 27 people had developmental delay or intellectual disability (100 percent)
  • 23 out of 27 people had language delays or impairment (85 percent)

Behavior

Many people with HIVEP2-related syndrome had behavioral challenges, such as autism or features of autism, ADHD, anxiety, aggressive behavior, or impulsivity.

  • 10 out of 17 people had behavioral challenges (59 percent)
  • 5 out of 10 people had autism or features of autism (50 percent)
  • 1 out of 10 people had ADHD (10 percent)
  • 1 out of 10 people had anxiety (10 percent)

Brain

Some people with HIVEP2-related syndrome had seizures, brain changes on magnetic resonance imaging (MRI), and a smaller than average head size, or microcephaly. But, some people had a larger than average head size, or macrocephaly.

  • 5 out of 29 people had seizures (17 percent)
  • 7 out of 14 people had brain changes seen on MRI (50 percent)
  • 8 out of 27 people had microcephaly (30 percent)
17%
5 out of 29 people had seizures.
50%
7 out of 14 people had brain changes seen on MRI.
30%
8 out of 27 people had microcephaly.

Mobility

Everyone had motor delays. Some people had movement disorders and lower than average muscle tone.

  • 4 out of 10 people had a movement disorder (40 percent)
  • 20 out of 27 people had lower than average muscle tone (74 percent)

Feeding and digestion

Many people with HIVEP2-related syndrome had gastrointestinal issues, such as constipation and gastroesophageal reflux.

  • 16 out of 27 people had gastrointestinal issues (59 percent)

Vision

Many people with HIVEP2-related syndrome had vision issues. This included farsightedness (hyperopia), crossed eyes (strabismus), nearsightedness (myopia), and astigmatism (an imperfection of the eye that causes blurred distance and near vision).

  • 16 out of 27 people had vision issues (59 percent)

Where can I find support and resources?

Hope for HIVEP2

Hope for HIVEP2’s mission is to find the parents of other children with a HIVEP2 loss-of-function diagnosis and create a community to advocate for their children. As whole exome sequencing becomes more available, more children will be diagnosed. They need doctors and researchers involved to help them get on the map, and provide management and treatment options that allow their children to reach their full potential.

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 a published study about HIVEP2-related syndrome. Below you can find details about the study, as well as a link to a summary.

  • Steinfeld H. et al. Neurogenetics, 17, 159-164, (2016). Mutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic features www.ncbi.nlm.nih.gov/pubmed/27003583
  • Mo, A., Snyder, L. G., Babington, O., Chung, W. K., Sahin, M., & Srivastava, S. (2022). Neurodevelopmental profile of HIVEP2-related disorder. Developmental Medicine & Child Neurology, 64(5), 654-661. https://pubmed.ncbi.nlm.nih.gov/34704275/
  • Quental, R., Borges, J. P., Santos, H., & Leão, M. (2022). Expanding the phenotypic spectrum of HIVEP2-related intellectual disability: Description of two Portuguese patients and review of the literature. Molecular Syndromology, 13(5), 397-401. https://pubmed.ncbi.nlm.nih.gov/36588750/

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