Table 2

Main genes related to paroxysmal dyskinesias and seizures

Principal causative gene SLC2A1 PRRT2 PNKD KNCMA1 SCN8A ECHS1 and PDC deficiency
Gene characteristicsSolute carrier family 2 member 1.
This gene encodes a major glucose transporter in the blood–brain barrier.
Proline-rich transmembrane protein 2.
This gene encodes a transmembrane protein in the brain and spinal cord.
Paroxysmal non-kinesigenic dyskinesia.
This gene is thought to play a role in the regulation of myofibrillogenesis.
Potassium calcium-activated channel subfamily M alpha 1 involved in the control of smooth muscle tone and neuronal excitability.Sodium voltage-gated channel alpha subunit 8 involved in the rapid membrane depolarisation that occurs in excitable neurons.Enoyl-CoA hydratase, short chain 1 caused by mutations in one of the genes encoding the 3 PDC subunits (PDHA1, DLAT, PDHX).
Main clinical syndromePED.PKD.PNKD.PNKD + epilepsy.PKD + epilepsy.PED + epilepsy.
Phenomenology and clinical featuresDuration of episodes: few minutes up to 2 hours.
Frequency: once per day or few times per month.
Lower limb dystonia.
Duration of episodes: seconds to minutes.
Frequency: up to 100 times per day.
Dystonia, chorea, or athetosis—usually unilateral.
Duration of episodes: minutes to hours, sometimes up to a day.
Frequency: few episodes per week or just a few episodes in a lifetime.
Dystonia, chorea or athetosis involving one limb and gradually spreading to other limbs and face.
PNKD and epilepsy, either in the form of absence or GTC seizures.Focal, tonic, clonic, myoclonic and absence of seizures, along with episodes sometimes resembling PKD.Epilepsy and PED, usually embedded in a more complex syndrome of lactic acidosis and encephalopathy (Leigh-like syndrome).
TriggersProlonged exercise, and rarely by muscle vibration, cold or passive movements.Sudden movement, such as sudden acceleration or change in direction of movement, or startle.Caffeine, alcohol, fatigue or emotional stress.
Additional disorders related to causative geneGLUT1DS: early-onset refractory seizures and MDs (dystonia, chorea, myoclonus and PED).BFIS: AD syndrome characterised by brief seizures featuring motor arrest, cyanosis, hypertonia and limb jerks.
ICCA: infantile convulsions followed by PKD.
  • AD, autosomal dominant; BFIS, benign familial infantile seizures; ECHS1, gene encoding PDC subunits; GLUT1DS, glucose transporter type-1 deficiency syndrome; GTC, generalised tonic-clonic seizures;ICCA, infantile convulsions and choreoathetosis syndrome; KNCMA1, gene encoding for a subunit of a calcium-activated potassium channel; MDs, movement disorders; PDC, pyruvate dehydrogenase complex;PED, paroxysmal exercise-induced dyskinesia;PKD, paroxysmal kinesigenic dyskinesia;PNKD, paroxysmal non-kinesigenic dyskinesia;SCN8A, encodes the alpha subunit of the sodium channel Nav1.