Objective: To describe a new finding of weakness associated with RDP.

Background: RDP is caused by mutations of the ATP1A3 gene. The phenotype of RDP is typified by a bulbar-predominant dystonia with rapid symptom onset after physiological stress. The ATP1A3 gene encodes the α3 subunit of the Na+/K+ ATPase, expressed ubiquitously in neurons. Expression has been observed in heart tissue but not skeletal muscle. Weakness is not part of the phenotype. Based on anecdotal observations in our 50 ATP1A3 mutation-positive subjects (MPs) and 44 mutation-negative relatives (MNs), we tested the hypothesis that MPs are more likely to have bulbar but not limb weakness.

Method: Subjects were excluded if onset occurred prior to 18 months of age. Subjects either had a mutation in ATP1A3 or were family members of such individuals. All underwent a videotaped neurological exam, including cranial nerve evaluation, neck strength, and limb strength. We defined bulbar weakness as abnormality on testing of: CN 5 (masseter strength), 7 (eye and mouth closure against resistance), 9&10 (palatal elevation and gag), 11 (shoulder shrug), or 12 (midline and side to side movement). Limb weakness was defined as scores of < 5 on 0-5 strength testing (hand grip, biceps, triceps, hamstrings, and quadriceps).

Results: After subjects with missing data were excluded, bulbar weakness was calculated for 16 MPs and 8 MNs, and limb weakness for 18 MPs and 9 MNs. Significantly more MPs displayed bulbar weakness (81% vs 13%, p=0.0023). Limb weakness was not significantly different between MPs and MNs (39% vs 0%, p=0.059) than MNs.

Conclusion: Though weakness is not known to be part of the RDP phenotype, significantly more MPs display bulbar or limb weakness than MNs. Muscle weakness should be carefully assessed in dystonic patients, and may raise the suspicion for genetic dystonia when present. We will follow up our findings with electrophysiological and pathological analysis of muscle tissue in MPs.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/rdp-is-associated-with-bulbar-and-limb-weakness-broadening-the-phenotype-of-atp1a3-rapid-onset-dystonia-parkinsonism-rdp/