Abstract Details

Title RDP is associated with bulbar and limb weakness: broadening the phenotype of ATP1A3+ Rapid-Onset Dystonia-Parkinsonism (RDP).

Topic Movement Disorders

Presentation(s) S53 - Movement Disorders: Genetics and Clinical Features (3:41 PM-3:52 PM)

Poster/Presentation
Number 002

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 or limb weakness.

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

Design/Methods

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 21 MPs and 8 MNs, and limb weakness for 22 MPs and 9 MNs. Significantly more MPs displayed bulbar weakness (86% vs 13%, p=0.0005) and limb weakness (45% vs 0%, p=0.030) than MNs.

Conclusions

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 plan to follow up our findings with electrophysiological and pathological analysis of muscle tissue in MPs.

Authors/Disclosures
Ihtsham Haq, MD, FAAN (University of Miami Miller School of Medicine) PRESENTER	The institution of Dr. Haq has received research support from NINDS. The institution of Dr. Haq has received research support from the Parkinson's Foundation. The institution of Dr. Haq has received research support from NIMH.
Beverly Snively	The institution of Beverly Snively has received research support from National Institutes of Health. The institution of Beverly Snively has received research support from Duke Endowment. The institution of Beverly Snively has received research support from Department of Defense. The institution of Beverly Snively has received research support from PCORI.
Kathleen J. Sweadner, PhD (Massachusetts General Hospital and Harvard Medical School)	The institution of Dr. Sweadner has received research support from Hope for Annabel, AHC Foundation, and CureAHC. The institution of Dr. Sweadner has received research support from the Chan-Zuckerberg Initiative.
	No disclosure on file
Jared Cook	No disclosure on file
Laurie J. Ozelius, PhD	The institution of Dr. Ozelius has received research support from NIH. Dr. Ozelius has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
Christopher T. Whitlow, MD (Wake Forest School of Medicine)	Dr. Whitlow has nothing to disclose.
Allison Brashear, MD, MBA, FAAN (Univeristy of Buffalo)	Dr. Brashear has received personal compensation for serving as an employee of McKnight Brain Res Found. Dr. Brashear has received personal compensation for serving as an employee of American Board of Psychiatry and Neurology. Dr. Brashear has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for ABPN. Dr. Brashear has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for McKnight Brain Research Foundation i. Dr. Brashear has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Care Directions- start up . Dr. Brashear has stock in Caredirections . The institution of Dr. Brashear has received research support from NINDS. Dr. Brashear has received publishing royalties from a publication relating to health care. Dr. Brashear has received personal compensation in the range of $500-$4,999 for serving as a Special government employee and study section reviewer with NIH. Dr. Brashear has received personal compensation in the range of $0-$499 for serving as a Adminstrative board -travel reimbursement with AAMC.

��ɫ��

��ɫ��