Clinical Characteristics

The classical phenotype associated with ATP8A2 pathogenic variants is cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ). The majority of patients have no ambulatory skills and profound cognitive impairment.

Most of the reported cases are of pediatric-onset, with hypotonia and a delay in motor and cognitive milestones being common presenting features. However, less severe forms of the disease with near-normal cognition and gait acquisition have been reported.

Neurological manifestations:
•    Hypotonia
•    Developmental delay
•    Cerebellar ataxia
•    Cognitive impairment
•    Movement disorders: facial and upper limb dystonia, chorea/choreoathetosis, facial dyskinesias.
•    Ophthalmoplegia
•    Pyramidal syndrome
•    Spinal cord dorsal columns dysfunction
•    Deafness
•    Optic atrophy

Extra-neurological manifestations:
•    Microcephaly
•    Upturned nose
•    triangular face
•    Scoliosis
•    Pectum excavatum