ABOUT
What Is GNB1?
Clinical characteristics
According to the current Gene Review, 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
Formal diagnostic criteria has not been established for GNB1. The diagnosis of GNB1 is established through genetic testing. Many patients go through comprehensive DNA sequencing to detect the mutation.
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
GNB1 is typically caused by a de novo pathogenic variant. If the GNB1 pathogenic variant identified is not identified in one of the parents, the risk to sibilings is low but greater than that of the general population because of the possibility of parental germline mosaicism. Once the GNB1 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.