To date the condition appears to be fully penetrant, however the severity of symptoms can vary significantly in a family.
The main clinical features are summarised below (as extracted from Hemati et al. paper, currently in Press):
- Global developmental delay is seen in 100% of affected individuals. The delay is moderate to severe, with half of reported individuals being non-ambulatory and non-verbal.
- Seizures have been reported in around 50% of affected individuals, with a variety of epilepsy types reported, including generalized, focal, mixed as well as infantile spasms.
- Infantile hypotonia, which can evolve to hypertonia and spasticity, has been reported in 78% of affected individuals.
- Abnormalities on brain MRI have been reported in 52% of affected individuals. Findings include abnormal or delayed myelination, abnormal corpus callosum, cerebral volume loss, ventriculomegaly, cortical thickening, polymicrogyria, and cerebellar hypoplasia.
- Dystonia has been reported in 17% of individuals with GNB1 variants.
- Persistent failure to thrive/growth delay was seen in 21% of affected individuals. Neonatal poor feeding and weight gain has been observed in 55%, but most eventually outgrew their feeding difficulties.
- Dysmorphic features were documented in 24 of 34 (70%) of affected individuals, but taken together these features are inconsistent.
- Abnormal vision (strabismus, nystagmus, optic atrophy and cortical visual impairment) has been reported in 58% of individuals.
- Additional features
Other features reported in individuals with GNB1 variants include: gastrointestinal problems (recurrent constipation, cyclical vomiting, gastroesophageal reflux, and distended abdomen with cramps) in 61% of affected individuals, genitourinary anomalies in males (35% of males reported), cleft palate (14%), cardiovascular defects (11%), sensorineural hearing loss (6.5%), and cutaneous mastocytosis (11%).