16p11.2 Distal Deletion Syndrome

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.

Some people may have:

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

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

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.

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.

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.

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.

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

• 2 out of 6 had an ADHD diagnosis (33 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).

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.

• Chu C, Wu H, Xu F, et al. Phenotypes Associated with 16p11.2 Copy Number Gains and Losses at a Single Institution. Lab Med. 2020;51(6):642-648. doi:10.1093/labmed/lmaa026
• Hanssen R, Auwerx C, Jõeloo M, et al. Chromosomal deletions on 16p11.2 encompassing SH2B1 are associated with accelerated metabolic disease. Cell Rep Med. 2023;4(8):101155. doi:10.1016/j.xcrm.2023.101155
• Woodbury-Smith M, D’Abate L, Stavropoulos DJ, et al. The Phenotypic variability of 16p11.2 distal BP2-BP3 deletion in a transgenerational family and in neurodevelopmentally ascertained samples. J Med Genet. 2023;60(12):1153-1160. Published 2023 Nov 27. doi:10.1136/jmg-2022-108818
• Bachmann-Gagescu R, Mefford HC, Cowan C, et al. Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity. Genet Med. 2010;12(10):641-647. pubmed.ncbi.nlm.nih.gov/20808231
• Sadler B, Haller G, Antunes L, et al. Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis. J Med Genet. 2019;56(7):427-433. pubmed.ncbi.nlm.nih.gov/30803986