EBF3-Related Syndrome

EBF3-related syndrome happens when there are changes to the EBF3 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 EBF3-related syndrome 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 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 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 syndrome is 50 percent.

For a symptom-free sibling, a brother or sister, of someone who has EBF3-related syndrome, the risk of having a child who has the syndrome depends on the symptom-free sibling’s genes and their parents’ genes.

• If neither parent has the same gene change found in their child who has the syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who has EBF3-related syndrome.
• If one birth parent has the same gene change found in their child who has the syndrome, 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 syndrome, the symptom-free sibling’s chance of having a child who has EBF3-related syndrome is 50 percent.

For a person who has EBF3-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, at least 99 people with EBF3-related syndrome have been identified in a medical clinic, and about 50 have been described in medical research. The first case of EBF3-related syndrome was described in 2017.

People who have EBF3-related syndrome may look different. Appearance can vary and can include some but not all of these features:

• Certain facial features, including a triangular face
• Shorter than average height
• Single connected eyebrow, also called synophrys
• Small ears
• Roof of the mouth that is highly arched
• Crowded teeth
• Single crease on the palms of hands

Scientists and doctors have only just begun to study EBF3-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 EBF3-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.

The section includes medical information on about 66 people with EBF3-related syndrome described in research publications.

Speech and Learning

All people with EBF3-related syndrome had intellectual disability or developmental delay. Most people had speech delays.

• 66 out of 66 people had intellectual disability or developmental delay (100 percent)
• 18 out of 21 people had speech delay (86 percent)

Behavior

Some people had autism, features of autism, or attention deficit hyperactivity disorder (ADHD). Other behavioral changes, like self-harming behavior, were also reported. Some people had decreased pain sensitivity.

• 6 out of 51 people had autism (12 percent)
• 13 out of 51 people had ADHD (26 percent)
• 7 out of 51 people had decreased pain sensitivity (14 percent)

Sitting, walking, muscle tone, and motor concerns

Low muscle tone and ataxia were very common. Almost all did not meet developmental milestones.

Growth

About one-quarter of people had growth issues, like shorter than average height and head size.

• 14 out of 56 people had short height and smaller than average head size (25 percent)

Other body systems

Some people had gastrointestinal issues, like constipation, difficulty swallowing, gastroesophageal reflux, and frequent vomiting. Musculoskeletal issues included: concave chest; sideways curve of the spine, also called scoliosis; webbing of the second and third toes; and bilateral club foot.

Several people had urogenital issues, including renal dysplasia, undescended testes, bicornuate uterus, lack of bladder control, and vesicoureteral reflux.

Eye issues were common and included nearsightedness or crossed eyes, also called strabismus.

• 13 out of 51 people had gastrointestinal issues (26 percent)
• 14 out of 51 people had musculoskeletal issues (28 percent)
• 19 out of 59 people had urogenital issues (32 percent)
• 12 out of 14 people had strabismus (86 percent)