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.

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.

As of 2024, more than 150 people with 16p12.2 deletion syndrome have been described in medical research.

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

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

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)

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)

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