GNB1-Related Syndrome

GNB1-related syndrome is caused by changes in the GNB1 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 GNB1-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 GNB1-related syndrome, the sibling’s risk of having a child who has GNB1-related syndrome depends on the sibling’s genes and their parents’ genes.

• If neither parent has the same genetic variant causing GNB1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit GNB1-related syndrome.

As of 2024, over 73 people with GNB1-related syndrome have been identified in a medical clinic. 

People who have GNB1-related syndrome may look different. Appearance can vary and can include some but not all of these features: 

• Premature closing in the bones of a baby’s skull 
• Changes in skin pigment 
• Lower than average muscle tone

Scientists and doctors have only just begun to study GNB1-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 GNB1-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.

Speech and Learning  

Many people with GNB1-related syndrome had developmental delay or intellectual disability, usually moderate to severe impairment. About one-half of people were non-verbal, and expressive language (ability to express yourself) was usually more affected than receptive language (ability to understand language). 

• 71 out of 71 people had developmental delay or intellectual disability (100 percent) 

Behavior 

Behavioral issues occurred in people with GNB1-related syndrome, including repetitive and stereotypic behaviors, attention-deficit/hyperactivity disorder (ADHD), and/or autism spectrum disorder. Developmental regression was rare. 

• 15 out of 36 people had behavioral issues (42 percent) 
• 3 out of 57 people had developmental regression (5 percent) 

Brain 

Over one-half of people with GNB1-related syndrome had seizures and/or brain changes observed on magnetic resonance imaging (MRI). A few people had a larger than average head size (macrocephaly) or a smaller than average head size (microcephaly). Most people had low muscle tone (hypotonia). 

• 27 out of 51 people had seizures (53 percent) 
• 25 out of 50 people had brain changes on MRI (50 percent) 
• 9 out of 40 people had macrocephaly (23 percent) 
• 3 out of 40 people had microcephaly (8 percent) 
• 37 out of 49 people had hypotonia (76 percent)

Growth 

Obesity was a problem for about 1 in 5 people, but some people were underweight. People with obesity had hyperphagia (a feeling of extreme, insatiable hunger). Obesity might develop as early as 3 and a half years old. 

• 8 out of 42 people had obesity (19 percent) 

 Mobility 

 Most people who are able to walk, had issues with walking and frequent falls.

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 GNB1 – www.simonssearchlight.org/research/what-we-study/gnb1
• Simons Searchlight GNB1 Facebook community – https://www.facebook.com/groups/gnb1