Table 1

- Summary of phenotypes associated with ATP1A3 gene mutation.

Classical distinct phenotypesEmerging new phenotypes
AHCRDPCAPOSEIEERECA/FIPWEIntermediate phenotypes
6–18 monthsChildhood to adulthood6 months–5 yearsNeonatal periodChildhoodChildhood
Paroxysmal episodes of hemiplegia, bilateral hemiplegia, or quadriplegia Abnormal eye movements, monocular nystagmus, dystonia, autonomic disturbanceAbrupt onset dystonia with prominent dysarthria and dysphagia postural instability bradykinesia Rostro-caudal gradientCerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing lossEarly-onset epileptic encephalopathy, catastrophic epilepsy, refractoryAbrupt-onset ataxia after febrile illness, resembling encephalitis, relapsing course and then stable Evolution can be a mixed phenotype ataxia-dystoniaParoxysmal episodes of weakness, strabismus resembling AHC spells; ataxia, dystonia with rostro-caudal gradient as in RDP
E801N, E815K, G947R, S811PT613M, D903NE818KG358C, G358V, I363N,
E815K		R756, E818KR756

  • AHC - alternating hemiplegia of childhood, RDP - rapid-onset dystonia parkinsonism, CAPOS - cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss, EIEE - early infantile epilepsy and encephalopathy, RECA - relapsing encephalopathy with cerebellar ataxia Adapted from A. Capuano et al (The Cerebellum 2018)2