Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations
| Autor: | Nicolás Seleme, Patricia Orellana, Verónica Fernández, Jan Hauke, Christine Klein, Norbert Brüggemann, Alexander Schmidt, Teresa Parrao, Alfredo Ramirez, Detlef Kömpf, Pablo Venegas, Marianne Kägi, Christian Kubisch, Cristian Garrido, Pedro Chana, Johann Hagenah, Cecilia V. Rojas, Maria I. Behrens, Eric Hahnen, Rafael González, Ferdinand Binkofski |
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| Rok vydání: | 2010 |
| Předmět: |
Pathology
medicine.medical_specialty Pediatrics Neuropsychological Tests Parkinsonian Disorders medicine Humans Dementia Genetic Testing Spasticity Age of Onset Chile Cognitive decline Promoter Regions Genetic Anarthria Neurologic Examination Palsy biology Lenticular nucleus Parkinsonism Brain DNA Methylation medicine.disease biology.organism_classification Magnetic Resonance Imaging Pedigree Proton-Translocating ATPases Neurology Kufor Rakeb syndrome Disease Progression Neurology (clinical) medicine.symptom Psychology |
| Zdroj: | MOVEMENT DISORDERS Artículos CONICYT CONICYT Chile instacron:CONICYT |
| ISSN: | 0885-3185 |
| DOI: | 10.1002/mds.22996 |
| Popis: | We report the clinical features of the original Chilean family with Kufor-Rakeb syndrome (KRS) that led to the discovery of the ATP13A2 gene at the PARK9 locus. KRS is a rare juvenile-onset autosomal recessive disease characterized by progressive Parkinsonism, pyramidal signs, and cognitive decline in addition to vertical gaze palsy and facial-faucial-finger minimyoclonus. Neurological and neuropsychological examination during a 10-year period, videotaping, neuroimaging, and measurement of DNA methylation of the ATP13A2 promoter region were performed. The youngest 5 of 17 children of nonconsanguineous parents, carrying compound-heterozygous ATP13A2 mutations, had normal development until ages similar to 10 to 12 years, when school performance deteriorated and slowness, rigidity, and frequent falls developed. Examination revealed bradykinesia, subtle postural/action tremor, cogwheel rigidity, spasticity, upward gaze palsy, smooth pursuit with saccadic intrusions, and dementia. Additional signs included facial-faucial-finger minimyoclonus, absent postural reflexes, visual/auditory hallucinations, and insomnia. Levodopa response could not be fully judged in this family. T2* magnetic resonance imaging sequences revealed marked diffuse hypointensity of the caudate (head and body) and lenticular nucleus bilaterally. Disease progression was slow including epilepsy, cachexia, and anarthria. Four affected members died after 28.5 +/- 5.5 (mean +/- SD) years of disease. Two heterozygous carriers, the mother and eldest sibling, showed jerky perioral muscle contractions and clumsiness of hand movements. There was no significant correlation between DNA methylation of the ATP13A2 promoter region and disease progression. The marked caudate and lenticular nucleus T2*-hypointensity suggests that KRS might belong to the family of neurodegenerative diseases associated with brain iron accumulation. (C) 2010 Movement Disorder Society |
| Databáze: | OpenAIRE |
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