Overview
Kufor-Rakeb Syndrome (KRS), also known as PARK9, is a rare neurodegenerative disorder caused by mutations in the ATP13A2 gene. It was first reported by Nisipeanu et al. in 1994.
Clinical Features
The initial symptoms of KRS typically include:
- Parkinsonism
- Pyramidal signs
- Supranuclear palsy with upgaze paresis
- Dementia
Patients with KRS often experience a rapid progression to a bedridden state within 12 months. Rest tremor is notably absent. Bradykinesia and rigidity show a remarkable response to levodopa therapy; however, levodopa does not alleviate the pyramidal signs. Over time, the effectiveness of levodopa is limited due to the development of dyskinesia.
Other notable clinical features include:
- Mini-myoclonus affecting the face, tongue, and fingers
- Visual hallucinations
- Oculogyric crises
- Episodes of aggression and psychosis, including frank hallucinations
Imaging and Pathology
MRI scans of patients with KRS often reveal generalized atrophy of the cerebrum, cerebellum, and brainstem, as well as progressive atrophy of the pyramids. Additionally, there may be iron deposition in the globus pallidus, caudate, and putamen.
References
- Behrens MI, Bruggemann N, Chana P, et al. (2010) Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations. Mov Disord 25: 1929–37
- Nisipeanu P, Kuritzky A, Korczyn AD (1994) Familial levodoparesponsive parkinsonian-pyramidal syndrome. Mov Disord 9: 673–5
- Williams DR, Hadeed A, al-Din AS, et al. (2005) Kufor Rakeb disease: autosomal recessive, levodopa-responsive parkinsonism with pyramidal degeneration, supranuclear gaze palsy, and dementia. Mov Disord 20: 1264–71.
