Session Information
Date: Tuesday, September 24, 2019
Session Title: Dystonia
Session Time: 1:45pm-3:15pm
Location: Les Muses Terrace, Level 3
Objective: To revise diagnostic criteria for RDP based on a cohort of ATP1A3 mutation+ individuals.
Background: RDP is caused by mutations of the ATP1A3 gene. ATP1A3 encodes the α3 subunit of the Na+/K+ ATPase. The published diagnostic criteria for RDP include: a rostrocaudal gradient of symptom severity, bulbar dysfunction, rapid symptom onset. Characteristic features include physiological triggers and onset near adolescence. Our group examined whether the aforementioned criteria were diagnostic in our database of patients with ATP1A3 mutations.
Method: Subjects were excluded if onset occurred prior to 18 months of age, to exclude Alternating Hemiplegia of Childhood. Subjects either had a mutation in ATP1A3 or were family members of such individuals. All underwent a videotaped structured interview and exam. We analyzed the cohort with respect to rapidity of onset, bulbar symptoms, and a rostrocaudal symptom gradient. Rapid onset was defined as < 30 days. The gradient was defined via Burke-Fahn-Marsden Dystonia Rating Scale (BMFDRS) subscores.
Results: This yielded 50 mutation-positive subjects (MPs) and 44 mutation-negative relatives (MNs), with 10 distinct mutations across 19 unrelated families. None of the criteria were universally met by MPs. A rostrocaudal gradient was present in 6%. Bulbar symptoms occurred in 84%, and rapid onset in 70%. More MPs overall did display moderate to severe dystonia with speech or swallowing (61%), than arms (35%), legs (39%), or face (5%). Onset ranged from 2 to 59 years (mean 22.4, SD±12.1). 68% of MPs had triggers.
Conclusion: RDP patients do not universally display rapidity of onset, bulbar symptoms, or a rostrocaudal gradient of severity. The lack of a gradient cannot be used to exclude RDP. We believe this change stems from moving to quantitative assessments and distinguishing between facial and laryngeal dystonia. RDP should be considered in the differential for any rapid onset bulbar dystonia, and suspected even in patients with slower onset.
To cite this abstract in AMA style:
I. Haq, B. Snively, K. Sweadner, C. Suerken, J. Cook, L. Ozelius, C. Whitlow, A. Brashear. Quantitative assessments better delineate rare disease: reconsidering the diagnostic criteria in ATP1A3+ Rapid-Onset Dystonia-Parkinsonism (RDP) [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/quantitative-assessments-better-delineate-rare-disease-reconsidering-the-diagnostic-criteria-in-atp1a3-rapid-onset-dystonia-parkinsonism-rdp/. Accessed June 14, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/quantitative-assessments-better-delineate-rare-disease-reconsidering-the-diagnostic-criteria-in-atp1a3-rapid-onset-dystonia-parkinsonism-rdp/