Phenotypic and Molecular Analyses of X-linked Dystonia-Parkinsonism (“Lubag”) in Women

Department of Neurology, Mayo Clinic, 13400 E Shea Boulevard, Scottsdale, AZ 85259, USA.
JAMA Neurology (Impact Factor: 7.42). 01/2005; 61(12):1956-9. DOI: 10.1001/archneur.61.12.1956
Source: PubMed


X-linked dystonia-parkinsonism (XDP) or "lubag" is an X-linked recessive disorder that afflicts Filipino men, and rarely, women. Genetic confirmation is performed through haplotyping or detection of disease-specific changes in the DYT3 gene.
To describe the phenotypes and molecular data of 8 symptomatic female patients with XDP from 5 kindreds.
Case series.
The average age of onset of symptoms was 52 years (range, 26-75 years). Six of 8 patients had parkinsonism, whereas only 1 had dystonia. The initial symptom was focal tremor or parkinsonism in 4, chorea in 3, and focal dystonia (cervical) in 1. Seven of 8 patients had slow or no progression of their symptoms and required no treatment. The patient with disabling parkinsonism was responsive to carbidopa/levodopa. Seven were heterozygous for the XDP haplotype, whereas 1 was homozygous.
The phenotypes of female patients with XDP may include parkinsonism, dystonia, myoclonus, tremor, and chorea. The dystonia, if present, is mild and usually nonprogressive. Similar to men with XDP, parkinsonism is a frequent symptom in women. In contrast to men, affected women have a more benign phenotype, older age of onset, and milder course. Extreme X-inactivation mosaic may be a cause of symptoms in women with XDP, but a homozygously affected woman has also been observed.

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    • "Regarding manifesting females with XDP, an initial report alluded to a milder course and that they do not present with dystonia, or if they do, the dystonia is usually focal, non-progressive, and non-disabling.6 A scrutiny on the clinical profile of the affected females in the XDP registry indicate that their clinical presentation do not significantly vary from their male counterparts. "
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    ABSTRACT: The clinical phenotype of X-Linked Dystonia Parkinsonism (XDP) is typically one that involves a Filipino adult male whose ancestry is mostly traced in the Philippine island of Panay. Dystonia usually starts focally in the lower limbs or oromandibular regions, then spreads to become generalized eventually. Parkinsonism sets in later into the disease and usually in combination with dystonia. /DYT3/ and /TAF1/ are the two genes associated with XDP. An SVA retrotransposon insertion in an intron of /TAF1/ may reduce neuron-specific expression of the /TAF1/ isoform in the caudate nucleus, and subsequently interfere with the transcription of many neuronal genes. Polypharmacy with oral benzodiazepines, anticholinergic agents and muscle relaxants leaves much to be desired in terms of efficacy. The medications to date that may appear beneficial, especially in disabling dystonias, are zolpidem, muscle afferent block with lidocaine-ethanol and botulinum toxin type A. Despite the few cases undergoing deep brain stimulation, this functional surgery has shown the greatest promise in XDP. An illustrative case of XDP in a family depicts the variable course of illness, including a bout of "status dystonicus," challenges in therapy, reckoning with the social impact of the disease, and eventual patient demise. Indeed, there remains some gaps in understanding some phenomenological, genetic and treatment aspects of XDP, the areas upon which future research directions may be worthwhile.
    10/2010; 3(2):32-38. DOI:10.14802/jmd.10009

  • Advances in Inorganic Chemistry 01/2000; 50:359-407. DOI:10.1016/S0898-8838(00)50008-7 · 1.57 Impact Factor
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    ABSTRACT: With the renaissance of stereotactic pallidotomy for Parkinson’s disease in 1990s, pallidotomy has become increasingly used as an effective treatment for various manifestations of medically refractory dystonia. More recently, deep brain stimulation of globus pallidus internus (GPi) has been replacing pallidotomy. Although GPi DBS has great promise for treating dystonia, there are some disadvantages. We introduce our experiences in subthalamic nucleus (STN) DBS for primary dystonia and tardive dystonia in this chapter. We propose that STN DBS has the following advantages over GPi DBS: (1) symptomatic improvement is seen immediately after stimulation, allowing us to quickly select the most suitable stimulation parameters; (2) the stimulation parameters for the STN are lower than those used for the GPi, resulting in longer battery life; and (3) STN DBS results in better symptomatic control than GPi DBS in dystonia patients when our STN data is compared to that obtained by others with using the GPi as the target. We suggest that STN DBS may be the most appropriate surgical technique for dystonia.
    12/2006: pages 207-214;
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