GENE GUIDE

2p16.3 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 2p16.3 Deletion Syndrome.
a doctor sees a patient

What is 2p16.3 deletion syndrome?

2p16.3 deletion syndrome happens when a person is missing a piece of chromosome 2, one of the body’s 46 chromosomes. Chromosomes are structures in our cells that house our genes. The missing piece can affect learning and how the body develops.

2p16.3 deletion syndrome is also called NRXN1-related disorder. Both conditions are caused by a deletion in the NRXN1 gene, which is missing when a person has a 2p16.3 deletion. In 2p16.3 deletion syndrome or NRXN1-related disorder, there is one non-working or missing copy of the NRXN1 gene.

There is a different condition named Pitt Hopkins-like syndrome 2, which happens when a person has two NRXN1 genes that are either not working or missing.

Key Role

The 2p16.3 region plays a key role in the development of communication skills, social skills, and learning skills.

Symptoms

Because the 2p16.3 region is important in brain activity, many people who have 2p16.3 deletion syndrome have:

  • Developmental delay
  • Intellectual disability
  • Speech and language delay
  • Autism
  • Other behavior issues, such as attention-deficit/hyperactivity disorder, also called ADHD
  • Low muscle tone
  • Breathing issues
  • Constipation
  • Schizophrenia

What causes 2p16.3 deletion syndrome?

2p16.3 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 2p16.3 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 2p16.3 plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that 2p16.3 syndrome is often the result of a de novo variant in 2p16.3. Many parents who have had their genes tested do not have the 2p16.3 genetic variant found in their child who has the syndrome. In some cases, 2p16.3 deletion syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

2p16.3 deletion syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in 2p16.3 they will likely have symptoms of 2p16.3 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.

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 or I have 2p16.3 deletion syndrome?

No parent causes their child’s 2p16.3 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 2p16.3 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 2p16.3 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 2p16.3 deletion syndrome, the sibling’s risk of having a child who has 16p13.11 deletion syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing 2p16.3 deletion syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit 2p16.3 deletion syndrome. 
  • If one biological parent has the same genetic variant causing 2p16.3 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 2p16.3 deletion syndrome, the risk of having a child who has the syndrome is about 50 percent.

Do all people who have 2p16.3 deletion syndrome have symptoms?

As of 2024, at least 186 people with 2p16.3 deletion syndrome have been identified in a medical clinic.

Do people who have 2p16.3 deletion syndrome look different?

People who have 2p16.3 deletion syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Deep-set eyes
  • Broad nasal bridge
  • Bulbous nose tip
  • Flat mid-face
  • Ear defects
  • Wide mouth

How is 2p16.3 deletion syndrome treated?

At this point, there are no medicines designed to treat 2p16.3 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 2p16.3 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 published articles. It highlights how many people have different symptoms. See the Sources and references section of this guide for a list of articles.

Behavior and development concerns linked to 2p16.3 deletion syndrome

2p16.3 deletion syndrome is also called NRXN1-related syndrome. The information below includes people with a single variant in the NRXN1 gene and a full 2p16.3 deletion.

Speech and Learning

Most people with 2p16.3 deletion syndrome had some degree of intellectual disability. This ranged from mild to moderate. Children required a lot of learning support, including attending a special school where the right support was available. Some adults who had the syndrome required supervision.

  • 93 out of 100 people had global developmental delay (93 percent)

Most people with 2p16.3 deletion syndrome had problems with communication. They had trouble speaking and getting their message across to others. They had less trouble understanding words and sentences. People often started talking late, with their first words usually spoken around age 2.

  • 12 out of 95 people had a speech and language delay (13 percent)

Behavior

Some people with 2p16.3 deletion syndrome had autism or features of autism. They also had other behavior issues, such as attention-deficit/hyperactivity disorder, also called ADHD.

  • 38 out of 100 people had features of autism (38 percent)
  • 4 out of 44 people had ADHD (9 percent)

Brain

Some people with 2p16.3 deletion syndrome had seizures, brain changes on magnetic resonance imaging (MRI), and a smaller or larger than average head size.

  • 46 out of 95 people had seizures (48 percent)
  • 11 out of 27 people had MRI findings (41 percent)
  • 10 out of 48 people had macrocephaly (21 percent)
  • 3 out of 48 people had microcephaly (7 percent)
Human head showing brain outline
48%
46 out of 95 people had seizures.
41%
11 out of 27 people had MRI findings.
21%
10 out of 48 people had macrocephaly.
7%
3 out of 48 people had microcephaly.

Medical and physical concerns linked to 2p16.3 deletion syndrome

Sitting and walking

Children usually started sitting and walking late. Most started walking on their own around 18 months of age.

Muscle tone

Some people had low muscle tone. This can cause delays in rolling over, sitting, crawling, and walking. Low muscle tone may also cause feeding problems.

  • 24 out of 59 people had low muscle tone (41 percent)

Vision and hearing

Less commonly, people with 2p16.3 deletion syndrome had vision and hearing issues.

  • 5 out of 44 people had vision issues (11 percent)
  • 9 out of 104 people had hearing issues (9 percent)

Other findings

Some people had heart formation or heart function issues and skeletal defects.

  • 12 out of 60 people had heart issues (20 percent)
  • 14 out of 61 people had skeletal findings (23 percent)

Where can I find support and resources?

NRXN1 Network

The NRXN1 Netowrk aims to build a collaborative network of families, clinicians, and scientists in order to support individuals affected by NRXN1 disorder. By joining forces, we will raise awareness, improve our understanding, and accelerate the diagnosis and treatment of NRXN1 disorder.

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 2p16.3 deletion syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.

  • Sciacca, M., Marino, L., Vitaliti, G., Falsaperla, R., & Marino, S. (2022). NRXN1 deletion in two twins’ genotype and phenotype: A clinical case and literature review. Children (Basel), 9(5), 698. https://pubmed.ncbi.nlm.nih.gov/35626875/

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