Abstract Details

Title Phenotypic Variability in Patients with Pathogenic Variants in ATP1A2 and ATP1A3

Topic Child Neurology and Developmental Neurology

Presentation(s) S8 - State-of-the-art Diagnostics in Child Neurology (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Objective Describe the phenotypic variability of ATP1A2 and ATP1A3 associated disease.

Background ATP1A2 and ATP1A3 are paralogous genes that encode the α-2 and α-3 subunits of the Na/K-ATPase ion channels, which are predominantly expressed in the CNS. Variants in ATP1A2 and ATP1A3 are classically associated with paroxysmal movement disorders like familial hemiplegic migraine and alternating hemiplegia of childhood, though they are increasingly associated with a broader spectrum of phenotypes. Here we describe a large case series of 31 patients detailing the phenotypic breadth of these complex conditions.

Design/Methods This case series was conducted by retrospective chart review.

Results Of 31 patients, 24 presented with or developed seizures (77%), 20 had developmental delay (65%), which often preceded the episodes bringing them to clinical attention, 11 developed movement disorders (35%), 10 had initial episodes provoked by illness or fever (32%), and 7 had migraine (23%). Importantly 2 patients had recurrent apneic episodes (6%) and 2 patients had cardiac arrest (6%). 17 patients had variants in ATP1A2 (55%) and 14 in ATP1A3 (45%). Age of onset ranged from birth to 12 years. Severity was highly variable, including patients with isolated rare hemiplegic migraine, non-intractable seizures, and epileptic encephalopathy.

Conclusions Disease caused by pathogenic variants in ATP1A2 and ATP1A3 can present in a myriad of ways, with an equally wide range of severity. Seizures and developmental delay are the most common findings, with developmental delay often preceding medical attention. Patients also may present with movement disorders, encephalopathy, migraine, apneic episodes, or cardiac arrest. Initial episodes may be provoked by infection or fever. These cases highlight the importance of considering genetic testing in patients with many neurologic phenotypes, as these can have therapeutic implications—with calcium channel blockers such as verapamil and flunarizine, or memantine, an NMDA-receptor antagonist being used in patients with variants in ATP1A2 and ATP1A3.

Authors/Disclosures
Alyssa Runco, MD PRESENTER	Dr. Domingue has nothing to disclose.
Jesse Levine, MD, PhD	Dr. Levine has nothing to disclose.
Daniel Calame, MD, PhD (Baylor College of Medicine, Child Neurology)	Dr. Calame has nothing to disclose.

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