Acute and Episodic Movement Disorders: ATP1A3-Related Disorders as Differential Diagnosis
26 April 2017 (online)
Background/Purpose: Between 2004 and 2014, the primary genetic defect of three acute and episodic movement disorders, which have been known for decades, have been identified. It was shown that alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism (RDP), and CAPOS syndrome are all caused by heterozygous mutations in the ATP1A3 gene.
Methods: Systematic clinical and molecular characterization of patients with mutations in the ATP1A3 gene was done.
Results: We could show a substantial clinical overlap between AHC, RDP, and CAPOS syndrome. Specific symptoms and trigger mechanisms in these three disorders caused by heterozygous mutations in the ATP1A3 gene can lead to the right diagnosis. Genetic testing allows an accurate and fast diagnosis.
Conclusion: In patients with unclear acute and episodic movement disorders, an ATP1A3-related disorder should be taken into account. AHC, RDP, and CAPOS syndrome have historically been recognized as allelic disorders. By our analyses, it became clear that all three disorders are now been seen as specific clinical entities within a clinical continuum of ATP1A3-related disorders. Because the boundaries between these disorders are blurred, not every diagnostic criterion for each disorder must be existent. To clinically differentiate between an ATP1A3-related disorder and other neurometabolic or neurovascular disorders, the knowledge of specific symptoms and trigger mechanisms is expedient. Molecular testing confirms the diagnosis, avoids unnecessary diagnostic procedures, and enables the prediction of the potential clinical course.