Recent advances in neurogenetics have provided significant insight into the underlying mechanisms of episodic dyskinesias.
PRRT2 (Proline-Rich Transmembrane Protein 2): Mutated in most primary PKD cases. PRRT2 interacts with SNAP-25 at the presynaptic membrane, playing a key role in neurotransmitter release. Mutations disrupt basal ganglia circuit signaling.
PNKD (MR-1 Gene): Mutated in classic PNKD. The gene product shows homology to enzymes involved in the detoxification of methylglyoxal—a compound naturally present in coffee and alcohol, explaining why these beverages trigger attacks.
SLC2A1 (GLUT1 Transporter): Mutated in PED. Impaired glucose transport across the blood-brain barrier leads to an energy deficit in the basal ganglia during sustained physical activity.
