Clinical Spectrum of Kufor-Rakeb Syndrome in the Chilean Kindred with ATP13A2 Mutations
Artículo

Open/ Download
Publication date
2010Metadata
Show full item record
Cómo citar
Behrens Pellegrino, María Isabel
Cómo citar
Clinical Spectrum of Kufor-Rakeb Syndrome in the Chilean Kindred with ATP13A2 Mutations
Author
- Behrens Pellegrino, María Isabel;
- Brüggemann, Norbert;
- Chana, Pedro;
- Venegas Francke, Pablo;
- Kägi, Marianne;
- Parrao, Teresa;
- Orellana, Patricia;
- Garrido, Cristián;
- Rojas, Cecilia V.;
- Hauke, Jan;
- Hahnen, Eric;
- González Victoriano, Rafael;
- Seleme Herrero, Eduardo;
- Fernández, Verónica;
- Schmidt, Alexander;
- Binkofski, Ferdinand;
- Kömpf, Detlef;
- Kubisch, Christian;
- Hagenah, Johann;
- Klein, Christine;
- Ramírez, Alfredo;
Abstract
Abstract: 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 facialfaucial-
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 6 5.5 (mean 6 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.
Patrocinador
This study was supported by grants
from Hilde Ulrichs Foundation for Parkinson Research, the
NGFN plus (Parkinson’s Disease Network—Subproject ‘‘Recessive
Parkinsonism’’), Volkswagen Foundation, and Hermann
and Lilly Schilling Foundation to C.K. and Fondecyt
Project 1080569 to M.I.B.
Quote Item
Movement Disorders Vol. 25, No. 12, 2010, pp. 1929–1937
Collections