Abstracts

Rationale: During early childhood, a number of conditions present with paroxysmal symptoms concerning for seizures. Most patients get extensive diagnostic work-up including labs, imaging and exhaustive genetic testing. This often delays the diagnosis and treatment in rare genetic conditions that mimic childhood epilepsy syndromes. Alternating hemiplegia of childhood (AHC) is a rare and complex neurological disorder characterized by repeated attacks of hemiplegia/tetraplegia, paroxysmal disturbances (tonic/dystonic spells and monocular nystagmus), epileptic seizures, developmental delay and episodes of autonomic dysfunction with the onset of symptoms prior to 18 months of age and characteristic improvement of plegic attacks with sleep. A focus on detailed history with knowledge of diagnostic criteria allows for early identification and management of this complex disorder. Methods: Case of AHC with a previously unreported variant in ATP1A3, a gene encoding a Na/K-ATPase pump. Chart review and literature review of PubMed using the search terms: “Alternating Hemiplegia of Childhood” AND “ATP1A3”. Results: A 19 month-old male presented with quadriparesis, drooling and paroxysmal dystonic posturing with no electroencephalographic (EEG) correlation of paroxysmal events but abnormal baseline EEG. Initially diagnosed with epilepsy for abnormal eye movements and treated with increasing doses of antiepileptic medications with poor symptom control but significant adverse effects. A detailed clinical history and targeted genetic work up revealed AHC. The child is now improving on flunarizine. Genetic testing revealed a novel c.2393t>C (p.Leu798Pro) variant in the ATP1A3 gene previously not described in literature. Mutations in the ATP1A3 gene are identified as the primary cause of AHC, composing the majority of cases. Our search identified more than 85 different ATP1A3 mutations with a wide array of phenotypic presentation. Conclusions: AHC is a rare autosomal dominant condition that should be strongly considered for any child presenting with paroxysmal attacks of hemiparesis/dystonia on alternating sides, early onset seizures and monocular nystagmus without an EEG correlate. This condition often presents with seizures initially but subsquent neurological symptoms are commonly misdiagnosed leading to poor outcome. Awareness and early identification of AHC allows for targeted diagnostic work up, prompt treatment, appropriate genetic counselling and improved prognosis; offering patients a better quality of life overall.References:1. Brashear A, Sweadner KJ, Cook JF, et al. ATP1A3-related neurologic disorders. 2008 Feb 7 [Updated 2018 Feb 22]. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-20182. Sweney MT, Silver K, Gerard-Blanluet M, et al. Alternating hemiplegia of childhood: early characteristics and evolution of a neurodevelopmental syndrome. Pediatrics. 2009;123(3):e534-e541. doi:10.1542/peds.2008-2027.3. Carecchio M, et al. ATP1A3-related disorders:an update.European Journal of Paediatric Neurology. 2018;22(2):257-263.  Funding: None