Identification of a common set of features reflective of a syndrome resulting from mutations in GPT2 that render the protein nonfunctional is a more recent discovery. Based on the reported clinical phenotypes, GPT2-syndrome is a neurological syndrome with core features including intellectual disability; reduced brain growth; developmental delay, as well as regression of achieved milestones (e.g., walking); progressive motor symptoms, which may lead to spastic paraplegia; and seizures.
Although all features are not present in all patients, combined, features commonly reported in patients with mutations in GPT2 and reflective of the syndrome include:
- Reduced brain growth after birth, as indicated by smaller head circumference
- Delay in achieving milestones such as sitting up, walking, and talking
- Intellectual disability
- Nonverbal or limited language abilities
- Muscle weakness during infancy
- Small stature
- Drooling
- Overresponsive reflexes
- Muscle rigidity or spasticity affecting mobility and/or flexing
- Regression in motor function (e.g., walking ability)
- Spastic diplegia/paraplegia
- Seizures