Kufor-Rakeb Syndrome

Alternative Names

  • KRS
  • Parkinson Disease 9, Autosomal Recessive, Juvenile-Onset
  • PARK9
  • Pallidopyramidal Degeneration With Supranuclear Upgaze Paresis And Dementia
  • KRPPD

Associated Genes

ATPase 13A2
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WHO-ICD-10 version:2010

Diseases of the nervous system

Extrapyramidal and movement disorders

OMIM Number

606693

Mode of Inheritance

Autosomal recessive

Gene Map Locus

1p36.13

Description

Kufor-Rakeb syndrome is a rare autosomal recessive form of juvenile-onset atypical Parkinson disease (PARK9) associated with supranuclear gaze palsy, spasticity, and dementia. Some patients have neuroradiologic evidence of iron deposition in the basal ganglia, indicating that the pathogenesis of PARK9 can be considered among the syndromes of neurodegeneration with brain iron accumulation. [From OMIM]

Epidemiology in the Arab World

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Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
606693.1LebanonUnknownNo Parkinsonism; Supranuclear gaze palsy; ... NM_022089.3:c.1550C>THomozygousAutosomal, RecessiveEstrada-Cuzcano et al. 2017; Grünewald et al. 2012

Other Reports

Jordan

In 1994, Najim Al-Din et al. assigned the name of Kufor-Rakeb syndrome to a severe form of Parkinsonism similar to pallido-pyramidal syndrome in a consanguineous family. Phenotypically normal parents were cousins and had 10 children, five of which were affected (including one female), one of them died of a respiratory infection after suffering from severe spastic paraplegia. This pattern prompted Najim Al-Din et al. (1994) to suggest an autosomal recessive inheritance for the condition. Apart from rigidity, bradykinesia and a mask-like face, signs such as dementia, lack of intentional tremor and a supranuclear upgaze paresis separate this disorder from pallido-pyramidal syndrome. Moreover, the syndrome is identified as rapidly progressive with initial atrophy of the globus pallidus and pyramids and subsequent general atrophy of the brain and onset is juvenile and subacute. Levodopa therapy resulted in variable but dramatic improvement, limited to extrapyramidal manifestations, within 48 hours in all affected subjects. However, only those with the shortest disease duration were rendered almost normal regarding the extrapyramidal manifestations. Hampshire et al. (2001) investigated the syndrome more closely and identified it as a nigro-striatal-pallidal-pyramidal neurodegeneration in the same family and linked it to a fragment of 9cM between markers D1S436 and D1S2843 on 1p36. A maximum multipoint lod score of 3.6 was obtained for the region containing markers D1S1592, D1S2826, D1S2644, and D1S199. Williams et al. (2005) investigated the surviving four patients of this family to further characterize Kufor-Rakeb syndrome as a distinct illness. All survivors had a normal birth and achieved developmental milestones. Onset started with general weakness, muscle stiffness and lethargy and progressed rapidly to a deterioration of motor function accompanied by involuntary jerky movements, and total dependence for daily activities. Later signs include visual hallucinations and dementia. Levodopa response peaked in the initial phase with excellent results only to subside and decrease to no effect and even dystonic posturing in one of the siblings. Williams et al. (2005) suggested a cortical involvement due to a facial-faucial-finger mini-myoclonus specific to KRS and subcortical implication due to the supranuclear gaze palsy. Ramirez et al. (2006) confirmed the implication of the ATP13A2 in the degradation of nigral neurons by identifying a homozygous 22bp duplication in exon 16 in all affected members of the original Jordanian family.

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