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Last updated: 4/17/2024
Years published: 2024
NORD gratefully acknowledges Amanda Gerard, MS, CGC, Baylor College of Medicine/Texas Children’s Hospital and Margarita Saenz, MD, Clinical Genetics and Metabolism, Associate Clinical Professor, Co-Director Neurogenetics Clinics, Children’s Hospital Colorado, for the preparation of this report.
Summary
GNB1-related disorder is a genetic condition associated with moderate to severe developmental delay or intellectual disability, differences in the structure of the brain, low muscle tone in infancy and seizures.
GNB1-related disorder typically begins in infancy or early childhood. The most commonly noted characteristics that may be identified during this time include developmental delays, low muscle tone and seizures or infantile spasms. Other symptoms that may be identified during this time or later can include differences in the structure of the brain, abnormal movements or contractions of the muscles, reduced vision, growth delays and digestive or gastrointestinal problems.
The life expectancy of people with GNB1-related disorder is not well described, because most people who have been diagnosed with the condition are currently children or young adults. There is no cure for GNB1-related disorder and treatment is based on managing the symptoms that are present in the patient.
GNB1-related disorder is caused by a change (disease-causing variant) in the GNB1 gene and follows a dominant pattern of inheritance.
Introduction
GNB1-related disorder was first described in 2016 by Petrovski, et al. There are currently over 60 known individuals with a diagnosis of GNB1-related disorder.
The most common signs and symptoms of GNB1-related disorder are developmental delays and intellectual disabilities, which can range from mild to severe. Intellectual disability is the most common characteristic, but it may not be recognized until the child attends school. Some people with GNB1-related disorder can talk and walk independently and others cannot.
Approximately half of individuals with GNB1-related disorder have seizures. Many different seizure types have been reported, including tonic, absence, myoclonic, generalized tonic-clonic and focal seizures. Some infants have also had infantile spasms.
Other signs and symptoms that have been commonly reported include:
Other less common features that have been reported in a smaller number of people include:
GNB1-related disorder is caused by a disease-causing variant or a likely disease-causing variant in the GNB1 gene.
GNB1-related disorder is a dominant genetic condition. Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
There are over 60 individuals reported in the world with GNB1-related disorder. The condition is not currently known to be more common in any specific population or ethnic group.
Many genetic conditions are associated with developmental delays and seizures, so individuals with GNB1-related disorder are usually diagnosed with broad genetic tests such as whole exome sequencing or whole genome sequencing that look for variants in thousands of different genes. Gene panel tests that look for variants in a number or genes or analysis of the GNB1 gene only can also confirm the diagnosis, but these tests are ordered less frequently.
Chromosome microarray analysis (CMA) is a commonly ordered genetic test for developmental delay and/or seizures. Because GNB1-related disorder is caused by GNB1 gene variants, CMA would not be an appropriate test to identify most individuals affected with GNB1-related disorder.
Clinical Testing and Workup
The following tests and evaluations may be suggested for a child diagnosed with GNB1-related disorder:
There is currently no cure for GNB1-related disorder. Treatment is based on managing the symptoms that are present in the patient with therapies that are known to be effective for those symptoms. Treatment should include developmental therapies, seizure medications as needed and early intervention services if needed. There is no specific anti-seizure medication recommended for individuals with GNB1-related disorder.
Physical therapy and occupational therapy may be recommended to help with muscle tone and make recommendations about adaptive equipment.
Patients may be referred to an ophthalmologist for screening of cortical visual impairment (CVI) and crossed eyes (strabismus).
Nutrition and speech therapy may be recommended for growth and feeding concerns.
Patients may be referred to a dermatologist for cutaneous mastocytosis and itchy skin concerns.
Genetic Counseling is recommended for families to provide support and discuss risks for future children.
Parents and physicians can submit clinical information on newly diagnosed individuals to the GNB1 Human Disease Genes website. This resource was established by physicians from Columbia University to clarify the clinical phenotype associated with pathogenic variants in the complete coding region of GNB1 and to facilitate research into the underlying mechanism of GNB1 encephalopathy.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLE
Hemati P, Revah-Politi A, Bassan H, et al. Refining the phenotype associated with GNB1 mutations: Clinical data on 18 newly identified patients and review of the literature. Am J Med Genet A. 2018;176(11):2259-2275. doi:10.1002/ajmg.a.40472
INTERNET
Revah-Politi A, Sands TT, Colombo S, et al. GNB1 Encephalopathy. 2020 Mar 5 [Updated 2021 Apr 15]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554743/ Accessed March 7, 2024.
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