16p12.2 Deletion Syndrome
16p12.2 deletion syndrome is also called 16p12.2 microdeletion. For this webpage, we will be using the name 16p12.2 deletion syndrome to encompass the wide range of variants observed in the people identified.
What is 16p12.2 deletion syndrome?
16p12.2 deletion syndrome happens when a person is missing a piece of chromosome 16, 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.
Key Role
The 16p12.2 region plays a role in brain development.
Symptoms
Because the 16p12.2 region is important for brain activity, many people who have 16p12.2 deletion syndrome have:
- Developmental delay
- Intellectual disability
- Speech delay
- Slow growth
- Behavioral issues, such as autism, bipolar disorder, depression, and schizophrenia
- Seizures
- Heart structure changes
- Sleep issues
What causes 16p12.2 deletion syndrome?
16p12.2 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 16p12.2 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 16p12.2 plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that 16p12.2 deletion syndrome is often the result of a de novo variant in 16p12.2. Many parents who have had their genes tested do not have the 16p12.2 genetic variant found in their child who has the syndrome. In some cases, 16p12.2 deletion syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
16p12.2 deletion syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in 16p12.2 they will likely have symptoms of 16p12.2 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
Why do I or my child have 16p12.2 deletion syndrome?
No parent causes their child’s 16p12.2 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 16p12.2 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 16p12.2 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 16p12.2 deletion syndrome, the sibling’s risk of having a child who has 16p12.2 deletion syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing 16p12.2 deletion syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit 16p12.2 deletion syndrome.
- If one biological parent has the same genetic variant causing 16p12.2 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 16p12.2 deletion syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have 16p12.2 deletion syndrome?
As of 2024, more than 150 people with 16p12.2 deletion syndrome have been described in medical research.
Do people who have 16p12.2 deletion syndrome look different?
People who have 16p12.2 deletion syndrome may look different. Appearance can vary and can include some but not all of these features:
- Small head, also called microcephaly
- Wide, flat forehead
- Widely spaced eyes
How is 16p12.2 deletion syndrome treated?
Scientists and doctors have only just begun to study 16p12.2 deletion 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 16p12.2 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/…t-is-epilepsy/seizure-types
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.
Behavior and development concerns linked to 16p12.2 deletion syndrome
Depending on the specific 16p12.2 deletion, the 16p12.2 region may have up to seven genes deleted. Some people inherit the 16p12.2 deletion from a parent who may or may not have medical features.
Speech and Learning
Many people with 16p12.2 deletion syndrome had developmental delay, intellectual disability, and speech delay. People with a 16p12.2 deletion are more likely to have learning disabilities, lower IQ, and memory issues.
- 76 out of 113 people had developmental delay (67 percent)
- 46 out of 59 people had intellectual disability (78 percent)
- 68 out of 92 people had speech delay (74 percent)
Behavior
People with 16p12.2 deletion syndrome had behavioral disorders, such as autism, features of autism, attention-deficit/hyperactivity disorder (ADHD), and aggression. In a smaller group of people, ten people with 16p12.2 deletion syndrome had psychiatric or behavioral disorders, such as schizophrenia, depression, psychiatric issues, or bipolar disorder. Researchers think that people with 16p12.2 deletion syndrome might have a higher rate of schizophrenia.
- 31 out of 67 people had autism (46 percent)
- 9 out of 16 people had a psychiatric or behavioral disorder (56 percent)
Brain
About 1 in 3 people with 16p12.2 deletion syndrome had seizures or a smaller than average head size, also called microcephaly. Some seizure types included West syndrome, Lennox-Gastaut syndrome, staring spells, epilepsy with myoclonus, and febrile seizures. Over one-half of people had brain changes observed on magnetic resonance imaging (MRI), such as cerebellar and cerebral atrophy, decreased white matter, unspecified periventricular changes, and agenesis of the corpus callosum.
- 27 out of 71 people had seizures (38 percent)
- 25 out of 81 people had microcephaly (31 percent)
Medical and physical concerns linked to 16p12.2 deletion syndrome
Muscles and growth
Over one-half of people with 16p12.2 deletion syndrome had musculoskeletal features. Some people had lower than average muscle tone (hypotonia) or growth issues, such as growth restriction in utero, short height and/or delayed growth.
- 30 out of 57 people had musculoskeletal features (53 percent)
- 24 out of 71 people had hypotonia (34 percent)
- 26 out of 74 people had growth restriction (35 percent)
Birth findings
Some people with 16p12.2 deletion syndrome had birth defects. Some people had heart findings, such as hypoplastic left heart, ventricular septal defect, patent foramen ovale, absence of posterior pericardium, bicuspid aortic valve, aortic valve stenosis, patent ductus arteriosus, and tetralogy of Fallot.
Other issues included hearing loss, kidney findings, males with genital defects, cleft palate, clubfoot, and bowed legs.
- 13 out of 34 people had heart findings (38 percent)
- 12 out of 47 people had genital defects (25 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.”
- Learn more about Simons Searchlight: www.simonssearchlight.org/frequently-asked-questions
- Simons Searchlight webpage with more information on 16p11.2 deletion: www.simonssearchlight.org/research/what-we-study/16p12-2-deletion
- Simons Searchlight Facebook group: https://www.facebook.com/groups/16p12-2-deletion
Sources and References
The content in this guide comes from published studies about 16p12.2 deletion syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.
- Girirajan, S., Pizzo, L., Moeschler, J., & Rosenfeld, J. 16p12.2 recurrent deletion. 2018 Sep 13. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK274565/
- Martin, J., Hosking, G., Wadon, M., Agha, S. S., Langley, K., Rees, E., Owen, M. J., O’Donovan, M., Kirov, G., & Thapar, A. (2020). A brief report: De novo copy number variants in children with attention deficit hyperactivity disorder. Translational Psychiatry, 10(1), 135. https://pubmed.ncbi.nlm.nih.gov/32398668/
- Uppinkudru, C., Basavaraju, R., Udupi, G. A., & Mehta, U. M. (2024). Schizophrenia in the context of neurodevelopmental disorders in 16p12.2 chromosomal deletion: A case report. Indian Journal of Psychological Medicine, 46(3), 283-284. https://pubmed.ncbi.nlm.nih.gov/38699775/