ATP1A3 mutations What is the phenotype?

Rapid-onset dystonia-parkinsonism (RDP) occurs in children over 18 months of age, teens, and adults, and alternating hemiplegia of childhood (AHC) occurs in children less than 18 months. They appear to be different diseases, but both are caused by mutations in ATP1A3.(1-4)ATP1A3 encodes the subunit of the Na+/K+-ATPase that is partially responsible for maintaining the electrical gradient in neurons. Motor symptoms, particularly dystonia, are obvious in both RDP and AHC, but RDP is predominantly fixed and AHC is known for its episodic and fluctuating course. There is now a broader phenotypic spectrum of RDP than originally described in 1993,(5,6) including psychosis,(7) new phenotypes in children,(8) and late onset.(9) The nonmotor phenotypes of both RDP (cognitive and psychiatric) and AHC (developmental delay, cognitive, and behavioral)(10,11) suggest that ATP1A3 mutations may play a role in other neurologic and psychiatric disorders. Mutations causing RDP or AHC cause symptoms such as dystonia, parkinsonism, epilepsy (including status epilepticus), hemiplegic episodes, abnormal ocular movements, developmental delay, psychosis, depression, anxiety, and gait disorders in ages ranging from newborns to age 87 years. It is likely that there will be a broad continuum of patients found, and even a role for the gene in polygenic disorders.