GPT2

Clinical Characteristics

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