ANK3-Related Syndrome

ANK3–related syndrome happens when there are genetic variants in both copies of the ANK3 gene or one loss of function variant in this gene. These variants can keep the gene from working as it should, and they can lead to brain development or function issues.

Autosomal dominant conditions

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 a gene change in ANK3 depends on the genes of both birth parents.

• If neither birth parent has the same gene change found in their child, the chance of having another child who has the gene change 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 change in the gene.
• If one birth parent has the same gene change found in their child, the chance of having another child who has the gene change is 50 percent.

For a symptom-free sibling, a brother or sister, of someone who has a gene change in ANK3, the risk of having a child who has a similar gene change depends on the symptom- free sibling’s genes and their parents’ genes.

• If neither parent has the same change to ANK3 found in their child who has the gene change, the symptom-free sibling has a nearly 0 percent chance of having a child who has the gene change.
• If one birth parent has the same gene change found in their child who has the gene change, the symptom-free sibling has a small chance of also having the same gene change. If the symptom-free sibling has the same gene change as their sibling who has the gene change, the symptom-free sibling’s chance of having a child who has a similar gene change is 50 percent.

For a person who has a gene change in ANK3, the risk of having a child who has a similar gene change is about 50 percent.

Autosomal recessive conditions

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 the same biological parents to a child with an autosomal recessive genetic condition, having another child who has GENE-related syndrome is almost always 25 percent.
• The chance of two carrier parents having a child who is also a carrier is 50 percent. Carriers are not expected to have symptoms. 
• The chance of them having a child who is not a carrier at all is 25 percent.

For a person who has GENE-related syndrome, the risk of having a child who has the same syndrome depends on their partner. 

• If their partner is a carrier, they have a 50 percent chance of having a child who has the syndrome and a 50 percent chance of having a child who is a carrier. 

If their partner is not a carrier, they have nearly a 0 percent chance of having a child who has the syndrome and a 100 percent chance of having a child who is a carrier.

As of 2024, at least 20 people with ANK3-related syndrome have been described in medical research.

It is unknown whether people with ANK3-related syndrome look different.

Scientists and doctors have only just begun to study people who have changes in the ANK3 gene. At this point, there are no medicines designed to treat the condition. 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 people who have autism 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.

Researchers are now finding that genetic variants in ANK3 associated with autism can be caused by one loss of function ANK3 variant or two ANK3 genetic variants.

Below, we have summarized the medical features identified for these two neurodevelopmental conditions.

Some genetic variants in ANK3 are associated with heart conditions, such as arrhythmogenic cardiomyopathy or Brugada syndrome.

Speech and Learning

All people with ANK3 genetic variants had developmental delay or intellectual disability and speech delay.

• 13 out of 13 people had developmental delay or intellectual disability (100 percent)
• 11 out of 11 people had language delay (100 percent)

Behavior

Some people with ANK3-related syndrome caused by a loss of function variant had features of autism, attention deficit hyperactivity disorder, or ADHD, and aggression.

• 5 out of 7 people had features of autism (71 percent)
• 2 out of 7 people had ADHD (29 percent)
• 2 out of 7 people had aggression (29 percent)

Some people with two ANK3 genetic variants also had hyperactivity and aggressive behavior.

• 3 out of 4 people had ADHD (75 percent)
• 4 out of 4 people had aggression (100 percent)

Brain

Some people with ANK3-related syndrome had seizures in infancy or childhood; either a larger than average head size, called macrocephaly, or a smaller than average head size, called microcephaly; and brain changes seen on magnetic resonance imaging (MRI).

• 4 out of 11 people had seizures (36 percent)
• 2 out of 9 people had larger than average head size (22 percent)
• 4 out of 9 people had smaller than average head size (44 percent)
• 3 out of 7 people had brain changes on MRI (43 percent)

Mobility

People who have ANK3-related syndrome had movement issues and lower than average muscle tone. Movement issues included spasticity, ataxia, and stereotypic limb movements.

• 6 out of 11 people had a movement disorder (55 percent)
• 8 out of 11 people had low muscle tone (73 percent)