GENE GUIDE

16p11.2 Distal Deletion 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 16p11.2 Distal Deletion Syndrome.
a doctor sees a patient

What is 16p11.2 distal deletion syndrome?

Sometimes people are born with extra or missing sections of chromosomes. 16p11.2 distal deletion syndrome happens when someone has a missing piece of chromosome 16, one of the body’s 46 chromosomes.

On your genetics report, you might see the words distal and proximal. A 16p11.2 distal region is between Break Point 2 (BP2) and Break Point 3 (BP3) of the chromosome. The proximal duplication is between Break Point 4 (BP4) and Break Point 5 (BP5).

Key Role

16p11.2 distal deletion syndrome can affect communication, social, and learning skills. There are 9 genes in the recurrent distal deletion. The number of genes deleted can vary from person to person. It is unclear which genes are associated with neurodevelopmental features.

Symptoms

Some people may have:

  • Obesity
  • Developmental delay or intellectual disability
  • Speech delay
  • Affected communication, social, and learning skills

What causes 16p11.2 distal deletion syndrome?

16p11.2 distal deletion syndrome happens when someone is missing a small piece of a specific region of chromosome 16, one of the body’s 46 chromosomes. Chromosomes are structures in our cells that house our genes.

We inherit chromosomes from our parents. When the sperm from the father joins the egg from the mother, they form a single cell with 46 chromosomes — 23 from the mother and 23 from the father. This cell then makes many copies of itself.

Some people inherit a genetic change from a parent. In other people, small mistakes can occur when genes are being copied. Parts of the chromosomes can break off, make extra copies, or end up in a different order than expected. When this happens, it is called a “de novo”, or new, change. The child can be the first in the family to have the genetic change.

Part of chromosome 16, known as the short arm or 16p, is prone to mistakes, such as extra or missing copies. This specific region of chromosome 16p is linked to different symptoms. For example, a different, more common deletion in the same general region of chromosome 16, known as 16p11.2, has been linked to autism, intellectual disability, and schizophrenia. The region of chromosome 16 missing in this syndrome — known as the ‘distal 16p11.2’ chromosomal region — is associated with similar conditions.

Dominant Inheritance

Children have a 50% chance of inheriting the genetic change

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 do I or my child have 16p11.2 distal deletion syndrome?

No parent causes their child’s 16p11.2 distal deletion syndrome. We know this because no parent has any control over the chromosome 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 genetic change takes place on its own and cannot be predicted or stopped.

What are the chances that other family members or future children will have 16p11.2 distal deletion syndrome?

16p11.2 distal deletion 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 16p11.2 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 16p11.2 plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that 16p11.2 distal deletion syndrome is often the result of a de novo variant in 16p11.2. Many parents who have had their genes tested do not have the 16p11.2 genetic variant found in their child who has the syndrome. In some cases, 16p11.2 distal deletion syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

16p11.2 distal deletion syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in 16p11.2 they will likely have symptoms of 16p11.2 distal deletion 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.

Do all people who have 16p11.2 distal deletion syndrome have symptoms?

Not necessarily. Some people do not have any symptoms. Some people may not learn that they have this genetic change until it is found in their children.

Will all of the people in a family that have 16p11.2 distal deletion syndrome have the same symptoms?

Not necessarily. Family members who have the same chromosome change can have different symptoms.

What are the chances that other family members will have 16p11.2 distal deletion syndrome?

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 16p11.2 distal deletion 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 16p11.2 distal deletion syndrome, the sibling’s risk of having a child who has 16p11.2 distal deletion syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing 16p11.2 distal deletion syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit 16p11.2 distal deletion syndrome. 
  • If one biological parent has the same genetic variant causing 16p11.2 distal deletion syndrome, the symptom-free sibling has a 50 percent chance of also having the same genetic variant. If the symptom-free sibling has the same genetic variant, their chance of having a child who has the genetic variant is 50 percent.

For a person who has 16p11.2 distal deletion syndrome, the risk of having a child who has the syndrome is about 50 percent.

How many people have 16p11.2 distal deletion syndrome?

As of 2024, more than 75 people who have 16p11.2 distal deletion syndrome are participating in Simons Searchlight. The first case was found in 2010. There are likely many more undiagnosed people who have the syndrome. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

Do people who have 16p11.2 distal deletion syndrome look different?

People who have 16p11.2 distal deletion syndrome may look different. Doctors need to study more people with the syndrome to better understand these differences.

How is 16p11.2 distal deletion syndrome treated?

At this point, there are no medicines designed to treat 16p11.2 distal deletion 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
  • Developmental 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 16p11.2 distal deletion 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: epilepsy.com/learn/types-seizures.

This section includes a summary of information from major published articles and the Simons Searchlight quarterly registry report. It highlights how many people have different symptoms. To learn more about the articles, see the Sources and References section of this guide.

Behavior and development concerns linked to 16p11.2 distal deletion syndrome

In the 16p11.2 distal deletion, a gene called Src homology 2 B adapter protein 1 (SH2B1) has been suggested to be linked to a person having early onset obesity.

Brain and behavior 

Most people are suggested to have intellectual disability, and one-half have speech delays. Some people develop autism.

  • 16 out of 28 people have intellectual disability (57 percent)
  • 16 out of 28 have speech delays (57 percent)
  • 6 out of 28 have an autism diagnosis (21 percent)
57%
16 out of 28 have intellectual disability.
57%
16 out of 28 have speech delays.
21%
6 out of 28 have an autism diagnosis.

Some have been reported to have behavior issues or attention deficit hyperactivity disorder, also called ADHD.

  • 9 out of 28 had an ADHD diagnosis (32 percent)

Other features

People with 16p11.2 distal deletion syndrome may develop obesity.

  • 16 out of 66 people with 16p11.2 distal deletion syndrome develop obesity (24 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.”

Sources and references

The content in this guide comes from published studies on 16p11.2 distal deletion syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.