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Understanding XDP through imaging,pathology,and genetics.


Paul Matthew D. Pasco,
Claro V. Ison,
Paul Matthew D. Pasco,
Edwin L. Muñoz,
Nelma S. Magpusao,
Anthony E. Cheng,
Kenneth T. Tan,
Raymundo W. Lo,
Rosalia A. Teleg,
Marita B. Dantes,
Ruth  Borres,
Elma  Maranon,
Cynthia  Demaisip,
Marita V. Reyes,
Lillian V. Lee

Related Institution

Roxas City Health Office, Roxas City

Child Neurosciences Center - Philippine Children's Medical Center

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Publication Information

Publication Type
Publication Sub Type
Journal Article, Original
The Philippine Journal of Neurology
Publication Date
August 2012


The X-linked dystonia-parkinsonism (XDP) is a severe progressive, adult-onset X-linked endemic disorder in Filipinos, which is characterized by dystonic movements that start in the third of fourth decade, and replaced by parkinsonism beyond the 10th year of illness. Understanding the pathophysiology of XDP and development of rational therapies will depend on observations from imaging pathological and genetic studies. In this paper we summarize the results of these studies on patients with XDP. The cranial magnetic resonance imaging shows hy-perintense putaminal rim in both dystonic and parkinsonian stages, and atrophy of the caudate head or putamen in the parkinsonian stage. Neuropathological findings show atrophy of the caudate nucleus and putamen, with mild to severe neuronal loss and gliosis. In the neostriatum, the dystonic phase of XDP shows the involvement of striosomes and matrix sparing, while the later, i.e., p[arkinsonian phase, shows matrix involvement as well. In the dystonic phase, the loss of striosomal inhibitory projections lead to disinhibition of nigral dopaminergic neurons, perhaps resulting in a hyperkinetic state; while in the parkinsonian phase, severe and critical reduction of matrix-based projection may result in extranigral parkinsonism. Genetic sequencing of the XDP critical region in Xq13.1 has revealed an SVA retronsposon insertion in an intron of TAF1. This may reduce neuron-specific expression of the TAF1 isoform in the caudade nucleus, and subsequently interfere with the transcription of many neuronal genes, including DRD2. Findings from imaging, pahtology, and genetics studies are gradually shedding light on the pathophysiology of XDP, which hopefully will lead to mare rational and directed therapies.


1. Altrocchi , P H, Forno, L S. "Spontaneous oral-facial dyskinesia: Neuropathology of a case. " Neurology 33, 801-805, 1983
2. Eidelberg, D , Takikawa, S , Wilhelmsen, K , Dhawan, V , Chaly, T . "Positron emission tomographic findings in Filipino X-linked dystonia-parkinsonism." Annals of Neurology 34, 185-91, 1993
3. Shimazu, H , Kyratsu, J , Hirano, A , Kaji, R . "Func-tional anatomy of the basal ganglia in X-liked recessive dystonia-parkinsonism." Annals of Neurology 58(1): 7-17, 2005
4. Graeber, M B, Kupke, K G, Muller, U . "Delineation of the dystonia-parkinsonism syndrome locus in Xq 13" Genomics 89, 8245-8248, 1992
5. Graybiel, A M, Canales, J , Capper-Loup, C . "Levodopa-induced dyskinesias and dopamine-dependent stereotypies: A new hypothesis. " Trends in Neurosciences, 23(suppl), 571-577; 6. 23(suppl): S51-S77, 2000
6. Haberhausen, G , Schmitt, I , Kohler, A , Peters, U , Rider, S , Chelly, J , et, al . "Assignment of the dystonia-parkinsonism syn-drome locus, DYT3, to a small region within a 1.8 Mb YAC contig of Xq13.1." The American ]ournaLof Human Genetics 57, 644-650, 1995
7. Kupke, K G, Lee, L V, Viterbo, G H, Arancillo, J , Donlon, T , Muller, U . "X-linked recessive torsion dystonia in the Philippines." American Journal of Medical Genetics 36, 237-242, 1990
8. Kupke, K G, Lee, L V, Muller, U . "Assignment of the X-linked torsion dystonia gene L Xq21 by linkage analysis." Neu-rology 40(1438-1442):
9. Lee, L V, Maranon, E , Demaisip, C , Peralta, O , Borres-Icasiano, R , Arancillo, J , et, al . "The natural history of sex-linked reces-sive dystonia parkinsonism of Panay, Philippines (XDP)." Parkin-,sonism and Related Disorders 9, 29-38, 2002
10. Lee, L V, Munoz, E L, Tan, K T, Reyes, M T. "Sex-linked recessive dystonia parkinsonism of Panay, Philippines (XDP)." Molecular Pathology 54, 362-368, 2001
11. Lee, L V, Pascasio, F M, Fuentes, F D, Viterbo, G H. "Torsion dystonia in Panay, Philippines." Advances in Neurology 14, 137-151, 1976
12. Makino, S , Kaji, R , Ando, S , Tomizawa, M , Yasuno, K , Goto, S , et, al . "Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism." The American Journal of Human Genetics 80, 393-406, 2007
13. Nolte, D , Niemann, S , MuIler, U . "Specific sequence changes in multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism. " Proceedings of the National Academy of Sciences of USA 100, 10347-1035, 2003
14. Tamiya, G , Makino, S , Kaji, R . "TAF1 as the most plausible disease gene for XDP/DYT3." The American Journal of Human Genet-ics 81, 417-418,
15. Waters, C H, Faust, P L, Powers, J , Vinter, H , Moskowitz, C , Nygaard, T , et, al . "Neuropathology of lubag (X-linked dystonia-parkinsonism)." Movement Disorders 8(3): 387-390, 1993
16. Wilhelmsen, K C, Moskowitz, C B, Weeks, D E, Neystat, M , Nygaard, T G, Clark, L , Dancoup, M , Sobrevega, E E, Ros-ales, R , Gamez, G L, Pacioles, O , Perez, M , Fahn, S . "Molecular genetic analysis of lubag. In S. Fahn (ed.), Dystonia 3: Advanceein Neurology Philadelphia, PA: Lippincort-Raven" 78, 341-348, 1998

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