Background Pathogenic variation in the ATP1A3 ‐encoded sodium‐potassium ATPase, ATP1A3, is responsible for alternating hemiplegia of childhood (AHC). Although these patients experience a high rate of sudden unexpected death in epilepsy, the pathophysiologic basis for this risk remains unknown. The objective was to determine the role of ATP1A3 genetic variants on cardiac outcomes as determined by QT and corrected QT (QTc) measurements. Methods and Results We analyzed 12‐lead ECG recordings from 62 patients (male subjects=31, female subjects=31) referred for AHC evaluation. Patients were grouped according to AHC presentation (typical versus atypical), ATP1A3 variant status (positive versus negative), and ATP1A3 variant (D801N versus other variants). Manual remeasurements of QT intervals and QTc calculations were performed by 2 pediatric electrophysiologists. QTc measurements were significantly shorter in patients with positive ATP1A3 variant status ( P <0.001) than in patients with genotype‐negative status, and significantly shorter in patients with the ATP1A3‐D801N variant than patients with other variants ( P <0.001). The mean QTc for ATP1A3‐D801N was 344.9 milliseconds, which varied little with age, and remained <370 milliseconds throughout adulthood. ATP1A3 genotype status was significantly associated with shortened QTc by multivariant regression analysis. Two patients with the ATP1A3‐D801N variant experienced ventricular fibrillation, resulting in death in 1 patient. Rare variants in ATP1A3 were identified in a large cohort of genotype‐negative patients referred for arrhythmia and sudden unexplained death. Conclusions Patients with AHC who carry the ATP1A3‐D801N variant have significantly shorter QTc intervals and an increased likelihood of experiencing bradycardia associated with life‐threatening arrhythmias. ATP1A3 variants may represent an independent cause of sudden unexplained death. Patients with AHC should be evaluated to identify risk of sudden death.

Author Contribution Statement: C. Ahn conceived and designed the study, acquired the data, and approved the version for publication. A. Niehaus participated in the collection and processing of dermatopathological materials. J. Pena analyzed and interpreted the data and constructed and edited the manuscript. P. A. Zameza and C. Ogbonna drafted and revised the manuscript. Data access statement: All data necessary for the case were provided as part of the case. Additional data may be provided upon request.

Ahn conceived and designed the study, acquired the data, and approved the version for publication. A. Niehaus participated in the collection and processing of dermatopathological materials. J. Pena analyzed and interpreted the data and constructed and edited the manuscript. P.A. Zameza and C. Ogbonna drafted and revised the manuscript. The authors declare no conflicts of interest. Data access statement: All data necessary for the case were provided as part of the case. Additional data may be provided on request.

Central centrifugal cicatricial alopecia (CCCA) is a common form of scarring alopecia that affects the crown or vertex of the scalp as centrifugally spreading patches of permanent hair loss. The etiology of CCCA is uncertain. Genetic predisposition, autoimmune diseases, infections (bacterial and fungal), and other idiopathic factors have all been explored as potential risk factors for the development of CCCA. Seborrheic dermatitis (SD) has been identified in a number of studies as the most common concurrent hair disorder seen in patients with CCCA. The high prevalence of SD in African American women and its association with long-term inflammation of the scalp may increase the likelihood of a connection between SD and other inflammatory conditions of the scalp in this population. Since it has frequently been discovered as a concomitant diagnosis in patients with CCCA, we hypothesize that a history of SD may play a role in the pathogenesis of CCCA.

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