Objective: To describe new genetic mutations and unusual clinical findings in two siblings with Kufor Rakeb syndrome, an autosomal recessive etiology of parkinsonism.

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 are sparse, with a good degree of clinical heterogeneity described.

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. Both patients progressed with findings of dystonia, especially prominent with gait, and falls. Cognitive issues were present in both patients, marked in the younger sibling, but of mild in the older sibling. Both patients had good response to levodopa, although the older sibling developed levodopa-induced dyskinesia with treatment.

Results: Here we describe two siblings with a rare genetic form of juvenile-onset parkinsonism with levodopa-responsive dystonia. Genetic testing revealed previously unreported mutations in both alleles; C1903T nonsense mutation (which was predicted to prematurely truncate the protein) and a deletion of exons 17-22.

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

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/kufor-rakeb-syndrome-with-prominent-dystonia-and-new-mutations-in-atp13a2-gene-in-two-siblings/