Abstract Details

Title Kufor-Rakeb Syndrome with Prominent Dystonia and New Mutations in ATP13A2 Gene in Two Siblings

Topic Movement Disorders

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 10-022

Objective

To describe a new genetic mutation and unusual clinical findings in two siblings with Kufor-Rakeb syndrome, a genetic etiology of juvenile-onset Parkinson’s disease.

Background Kufor-Rakeb syndrome (PARK9), is a rare form of autosomal recessive juvenile-onset atypical parkinsonism. Affected patients have been described with supranuclear gaze palsy, spasticity, dementia, myoclonus, and dystonia in addition to parkinsonian findings. Levodopa-responsiveness has been described. World-wide, the number of reported cases of this rare condition is sparse.

Design/Methods An 18 year-old presented to clinic with 4 years of difficulty with walking, which progressed to frank imbalance and falls. His younger brother also had problems with walking at the age of 12 years of age. Both patients progressed with findings of frank generalized dystonia, especially prominent with gait and falls. Cognitive issues were present in both patients, marked in the younger sibling, but of more recent origin in the older sibling. Both patients had good response to levodopa, although the older sibling has developed some limitations of levodopa-induced dyskinesia with treatment.

Results Here we describe two siblings with a rare genetic form of juvenile-onset Parkinson’s disease with levodopa-responsive dystonia. Genetic testing revealed previously unreported mutations in both alleles. A C1903T nonsense mutation was predicted to prematurely truncate the protein . The other mutation was a deletion of exons 17-22.

Conclusions

Kufor-Rakeb syndrome, a genetic cause of juvenile-onset Parkinson’s disease, is rare with limited cases reported in the literature. The genetic mutations found in these patients are novel and the presentation found in these siblings is unusual for the significant dystonia present. These cases demonstrate expansion of the clinical phenotype seen for this particular genetic mutation.

Authors/Disclosures
Tritia R. Yamasaki, MD, PhD, FAAN (University of Kentucky) PRESENTER	The institution of Dr. Yamasaki has received research support from Veteran's Affairs. The institution of an immediate family member of Dr. Yamasaki has received research support from Dept of Energy.
	No disclosure on file
	No disclosure on file
	No disclosure on file
John T. Slevin, MD, FAAN (University of Kentucky)	Dr. Slevin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. The institution of Dr. Slevin has received research support from Veterans Administration. The institution of Dr. Slevin has received research support from NIH. The institution of Dr. Slevin has received research support from AbbVie. The institution of Dr. Slevin has received research support from NeuroDerm. The institution of Dr. Slevin has received research support from Bukwang-Syneos. The institution of Dr. Slevin has received research support from Takeda.

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