Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations.
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Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations. / Behrens, Maria I; Brüggemann, Norbert; Chana, Pedro; Venegas, Pablo; Kägi, Marianne; Parrao, Teresa; Orellana, Patricia; Garrido, Cristian; Rojas, Cecilia V; Hauke, Jan; Hahnen, Eric; González, Rafael; Seleme, Nicolas; Fernández, Verónica; Schmidt, Alexander; Binkofski, Ferdinand; Kömpf, Detlef; Kubisch, Christian; Hagenah, Johann; Klein, Christine; Ramirez, Alfredo.
In: MOVEMENT DISORD, Vol. 25, No. 12, 12, 2010, p. 1929-1937.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations.
AU - Behrens, Maria I
AU - Brüggemann, Norbert
AU - Chana, Pedro
AU - Venegas, Pablo
AU - Kägi, Marianne
AU - Parrao, Teresa
AU - Orellana, Patricia
AU - Garrido, Cristian
AU - Rojas, Cecilia V
AU - Hauke, Jan
AU - Hahnen, Eric
AU - González, Rafael
AU - Seleme, Nicolas
AU - Fernández, Verónica
AU - Schmidt, Alexander
AU - Binkofski, Ferdinand
AU - Kömpf, Detlef
AU - Kubisch, Christian
AU - Hagenah, Johann
AU - Klein, Christine
AU - Ramirez, Alfredo
PY - 2010
Y1 - 2010
N2 - 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 ?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.
AB - 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 ?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.
KW - Humans
KW - Neuropsychological Tests
KW - Disease Progression
KW - Magnetic Resonance Imaging
KW - Age of Onset
KW - Pedigree
KW - Promoter Regions, Genetic
KW - Genetic Testing
KW - Chile
KW - DNA Methylation
KW - Neurologic Examination
KW - Brain/pathology/physiopathology
KW - Parkinsonian Disorders/genetics/pathology/physiopathology
KW - Proton-Translocating ATPases/genetics
KW - Humans
KW - Neuropsychological Tests
KW - Disease Progression
KW - Magnetic Resonance Imaging
KW - Age of Onset
KW - Pedigree
KW - Promoter Regions, Genetic
KW - Genetic Testing
KW - Chile
KW - DNA Methylation
KW - Neurologic Examination
KW - Brain/pathology/physiopathology
KW - Parkinsonian Disorders/genetics/pathology/physiopathology
KW - Proton-Translocating ATPases/genetics
M3 - SCORING: Journal article
VL - 25
SP - 1929
EP - 1937
JO - MOVEMENT DISORD
JF - MOVEMENT DISORD
SN - 0885-3185
IS - 12
M1 - 12
ER -
