ABOUT
What Is GNB1?
Clinical characteristics
GNB1 syndrome (or simply GNB1) is characterized by:
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Moderate to severe global developmental delay or intellectual disability
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Generalized hypotonia or low muscle tone (during infancy) that can evolve to hypertonia and spasticity.
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Feeding and weight gain difficulties
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Movement disorder (dystonia, tics, ataxia, and chorea)
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Epilepsy (including generalized, focal, and mixed epilepsy and infantile spasms)
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Behavior problems (repetitive and stereotypic behaviors, attention-deficit/hyperactivity disorder [ADHD], and/or autism spectrum disorder [ASD])
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Macrocephaly or large head circumference
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Slow growth
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Vision impairment (optic atrophy and cortical visual impairment) and/or abnormal eye movements (strabismus, nystagmus)
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Gastrointestinal issues (chronic constipation, cyclic vomiting, gastroesophageal reflux disease [GERD], and/or abdominal distention with cramps)
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Craniofacial anomalies (cleft palate, craniosynostosis)
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Cutaneous mastocytosis (a large number of mast cells that gather in the skin, causing bumps or spots)
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Characteristics may vary from person to person, even those with the same variants of the mutation.
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Diagnosis/Testing
There are many different genetic conditions that have symptoms such as seizures and developmental delay that are present in children with GNB1-related disorder. Distinguishing this condition from other conditions based on signs and symptoms can be challenging, therefore formal diagnostic criteria has not been established for GNB1. Diagnosis relies on genetic testing. Patients are usually diagnosed with broad DNA or genetic testing, such as whole exome sequencing or whole genome sequencing that look for variants in thousands of different genes.
What is GNB1?
G-proteins, or guanine nucleotide-binding proteins, are important molecules found in our cells that help transmit signals from outside the cell to its interior. G-proteins help cells communicate important information and respond to changes in their environment.
G-proteins are made up of an alpha, beta, and gamma subunit. GNB1 is the gene that encodes the beta subunit of the G-protein. Genes provide the information needed to make proteins. Changes (also known as mutations) in genes, can alter protein production and functioning. In the case of GNB1, mutations in this gene can affect the formation and function of the G-protein, which can affect various biological processes. Depending on the location of the mutation in the GNB1 gene, an individual might present as being on the autism spectrum or classified as having a severe movement disorder, such as cerebral palsy. Our community has reported over 80 variants of the GNB1 mutation.
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Genetic Counseling
GNB 1 is typically caused by de novo germline mutation (meaning that the change in the gene occurred spontaneously in a parent’s reproductive cells) and follows a dominant pattern of inheritance, passed down from parent to child. For parents with a child who has this spontaneous mutation, they are often told that there is a 1-2% chance that any future children could also have the same mutation. This is because parents can sometimes be genetic mosaics, meaning the mutation occurred in one parent earlier, affecting many of their sperm or egg cells. If the GNB1 mutation is found in the family, there are options like prenatal testing for pregnancies at higher risk and genetic testing before implantation. Genetic testing and counseling are recommended for parents of affected individuals to better understand the nature of the mutation, modes of inheritance, and make informed medical decisions.
