ZNF462-Related Syndrome

ZNF462-related syndrome happens when there are changes in the ZNF462 gene. These changes can keep the gene from working as it should.

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 ZNF462-related 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 ZNF462-related syndrome, the sibling’s risk of having a child who has ZNF462-related syndrome depends on the sibling’s genes and their parents’ genes. 

• If neither parent has the same genetic variant causing ZNF462-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit ZNF462-related syndrome. 
• If one biological parent has the same genetic variant causing ZNF462-related 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 ZNF462-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2026, about 83 people with ZNF462-related syndrome have been identified in a medical clinic.

People who have ZNF462-related syndrome may look different. Appearance can vary and can include some but not all of these features:

• A noticeable ridge at the center of the forehead
• Front of the head that appears pointed and triangular
• Drooping upper eyelids
• Arched eyebrows that meet in the center of the forehead
• Small and upturned nose, with a round tip
• Thin upper lip
• Uneven or large ear

Scientists and doctors have only just begun to study ZNF462-related 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 ZNF462-related 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: www.epilepsy.com/learn/types-seizures.

Learning and speech

Many people with ZNF462-related syndrome had developmental delay or intellectual disability, and speech delays.

• 40 out of 53 people had developmental delay (75 percent)
• 29 out of 53 people had intellectual disability (55 percent)

Behavior

People with ZNF462-related syndrome had behavioral issues, such as autism, attention-deficit/hyperactivity disorder (ADHD), or obsessive-compulsive disorder.

• 18 out of 52 people had autism (35 percent)

Brain

Some people with ZNF462-related syndrome had neurological medical issues, such as lower than average muscle tone (hypotonia) and brain changes seen on magnetic resonance imaging (MRI), including agenesis of the corpus callosum and dilated ventricles.

• 16 out of 51 people had hypotonia (31 percent)
• 12 out of 32 people had brain changes seen on MRI (38 percent)

Heart

People with ZNF462-related syndrome had heart issues, such as changes in the walls of the heart called persistent ductus arteriosus, atrial or ventricular septal defects, arrhythmia, or heart valve issues.

About 3 in 10 people with ZNF462-related syndrome had heart structure issues.

• 17 out of 51 people had heart issues (33 percent)

Feeding and digestion issues

People with ZNF462-related syndrome had feeding issues, and some had gastrointestinal issues.

• 16 out of 52 people had feeding issues (31 percent)

Vision and hearing

Vision issues included, but were not limited to, droopy eyelids (ptosis). Some people had hearing loss.

• 40 out of 52 people had ptosis (77 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 ZNF462: www.simonssearchlight.org/research/what-we-study/znf462

• Simons Searchlight ZNF462 Facebook community: https://www.facebook.com/groups/znf462