Kufor-Rakeb syndrome, pallido-pyramidal degeneration with supranuclear upgaze paresis and dementia, maps to 1p36
Kufor-Rakeb syndrome is an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration. The onset is in the teenage years with clinical features of Parkinson's disease plus spasticity, supranuclear upgaze paresis, and dementia. Brain scans show atrophy of the globus pallidus and pyramids and, later, widespread cerebral atrophy. We report linkage in Kufor-Rakeb syndrome to a 9 cM region of chromosome 1p36 delineated by the markers D1S436 and D1S2843, with a maximum multipoint lod score of 3.6.
(J Med Genet 2001;38:680-682)
Keywords: Kufor-Rakeb syndrome; autozygosity mapping; Parkinson's disease; chromosome 1p36
Parkinson's disease is a relatively common neurodegenerative disorder affecting approximately 1% of the population over the age of 50 years.  The aetiology is complex and currently undetermined but involves loss of the dopaminergic neurones of the nigro-striatal tract. [2 3] Since there is no known curative therapy, any Mendelian condition that manifests even some symptoms of idiopathic Parkinson's disease is of potential interest since insights into the perturbed neurophysiology found in such rare conditions may lead to novel therapies applicable to patients with the idiopathic form of the disease. We report our studies of a consanguineous Jordanian family with four members affected by Kufor-Rakeb syndrome, a neurodegenerative disorder involving the nigro-striatal tract, the globus pallidus, and the pyramids.
The Kufor-Rakeb syndrome was originally reported by Al-Din et al  where they described clinical findings in five affected offspring of a consanguineous couple. These subjects showed a number of the features seen in idiopathic Parkinson's disease including a mask-like face, rigidity, and bradykinesia but the onset of the condition was much earlier, between 11 and 16 years of age, and the disease was rapidly progressive. Quoting the original paper: "The features of paralysis agitans were remarkable in their rate of development rendering the patients bed-ridden within less than two years of onset". Therapy with levadopa resulted in significant improvement of extrapyramidal function for up to two years. Interestingly, intention tremor, a classical Parkinson's disease feature, was not seen. Additional disease features found in Kufor-Rakeb syndrome that are absent in idiopathic Parkinson's disease were spasticity resulting from corticospinal tract degeneration, a supra-nuclear upgaze paresis, and the development of dementia in all affected subjects. Although the Kufor-Rakeb syndrome has similarities to pallido-pyramidal syndrome, it seems to be distinguished as a separate entity by the presence of dementia and upgaze paresis seen in this family together with the lack of intention tremor. [4-7] The oldest affected subject, who had a severe spastic paraplegia, was aphasic and demented, has died following a respiratory infection. It was not possible to perform a necropsy. MRI brain scans of affected family members showed the progression of disease with initial atrophy of the globus pallidus and pyramids, and later generalised brain atrophy. 
The inheritance pattern of Kufor-Rakeb syndrome was considered to be...
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