MBD5-Related Syndrome

MBD5-related syndrome happens when there are changes in the MBD5 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 MAND 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 disorder 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 disorder is 50 percent.

For a symptom-free sibling, a brother or sister, of someone who has MAND, the risk of having a child who has the disorder 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 disorder, the symptom-free sibling has a nearly 0 percent chance of having a child who has MAND.
• If one birth parent has the same gene change found in their child who has the disorder, 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 disorder, the symptom-free sibling’s chance of having a child who has MAND is 50 percent.

For a person who has MAND, the risk of having a child who has the disorder is about 50 percent.

As of 2026, about 175 people with MBD5-related syndrome have been identified in a medical clinic.

People with MBD5-related syndrome may look different. Appearance can vary and can include, but is not limited to, these features:

• Smaller than average head size (microcephaly)
• Thick and highly arched eyebrows
• Forward-facing large earlobes
• Noticeable ears
• Short nose
• Depressed or wide bridge of the nose
• Downturned corners of the mouth
• Thin border of the upper lip

Scientists and doctors have only just begun to study MBD5-related syndrome. At this point, there are no medicines designed to treat the disorder. 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. These can include physical, occupational, speech, or behavioral therapy.
• Guide individualized education plans (IEPs).

Specialists advise that therapies for MBD5-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

Most people with MBD5-related syndrome had developmental delay and speech delay or impairment. Although children had motor, language, and social delays, they usually gained skills without regressions. The average age of walking was 2 to 3 years old. Most children did not speak or were able to speak in single words, short phrases, or sentences.

• 100 percent of people had a developmental delay
• 80 percent of people had a speech delay and/or language impairment

Behavior

Some people with MBD5-related syndrome had behavioral issues, such as autism or features of autism, attention-deficit/hyperactivity disorder (ADHD), repetitive behaviors (stereotypic behavior), self-injury and aggression, anxiety, inappropriate happy demeanor, and social withdrawal.

• 100 percent of people had behavioral issues
• 80 percent of people had repetitive behaviors
• 60 percent of people had self-injury and aggression

Other medical findings

People with MBD5-related syndrome often had feeding issues and constipation and many had skeletal defects. Skeletal changes included small hands and feet, the pinky finger curving at the joint, shorter fingers or toes, and a sandal gap (a wide gap between the big toe and second toe). A few people had heart defects, such as a hole in the heart (atrial septal defect or ventricular septal defect) or a narrowed heart valve (pulmonic stenosis).

• 90 percent of people had feeding issues and constipation
• 10 percent of people had heart defects