The Unique Phenomenology of Sex-Linked Dystonia Parkinsonism (XDP, DYT3, “Lubag”)

Abstract

Sex-linked dystonia parkinsonism (XDP, DYT3, "Lubag") is an adult-onset, progressive, debilitating movement disorder first described in Filipino males from Panay Islands in 1975. XDP manifests predominantly as torsion dystonia, later combined with or sometimes replaced with parkinsonism. Within the Island of Panay, the prevalence rate is highest in the province of Capiz, where 1:4000 men suffer from the disorder. There is a high degree of penetrance and generalization. While women often serve as carriers, XDP is not limited to men. An updated XDP Philippine registry (as of January 2010) has identified 505 cases, with 500 males and 5 females. While some report that females may carry a milder form of the disorder, in our experience, both sexes generally follow a similar progressive clinical course.

New insights into the genetics of X-linked dystonia-parkinsonism (XDP, DYT3)

“…Ninety-five percent of affected individuals are males; the average age is 44 years (20-70 years); and the average age at onset is 39 years (12-64 years). 2 The DYT3 disease locus has been mapped to an~427-kb region on Xq13.1 flanked by DXS10015 proximally and DXS559 distally, 3 however, previous studies did not reveal mutations in the coding regions of known genes inside this interval. [3][4][5][6] Instead, five disease-specific single-nucleotide changes (DSC1, DSC2, DSC3, DSC10, DSC12), one 48-bp deletion, and one 2627-bp SVA (SINE-VNTR-Alu element) retrotransposon insertion, all found either within 'deep intronic' or intergenic DNA segments, or in a nonconventional exon of the nearby TAF1 gene, have been identified only in affected individuals.…”

Long-Term Outcomes of Bilateral Pallidal Deep Brain Stimulation for X-Linked Dystonia and Parkinsonism

“…However, patients with XDP are at a greater risk of developing psychiatric and cognitive symptoms, with 93% suffering from depressive symptoms in one study [36] and suicide incidence accounting for 9% of mortality in another [7]. Transient worsening of depression occurred in 1 of our patients but improved with pharmacotherapy.…”

“…A case of XDP in a patient with atypical Turner’s syndrome [9] and a case due to skewed X-chromosome inactivation have been reported [8]. The estimated prevalence in the Philippines is 0.31/100,000 people, with a prevalence of 5.3/100,000 on the island of Panay [7]. …”

“…Parkinsonism usually presents later in the disease (the combined dystonia-parkinsonian phase) and, typically, 15 years after the onset of illness, parkinsonism becomes more prominent, manifesting with tremor, bradykinesia, hypomimia, drooling, and gait impairment (the parkinsonian phase). Malnutrition and aspiration pneumonia are the usual causes of death, and risk of suicide is higher in XDP than in the general population [7]. Imaging findings in XDP include hyperintensity of the rim of the putamen in the dystonic and parkinsonian phases, and caudate and putaminal atrophy during the parkinsonian phase [10].…”

“…XDP involves impaired expression of the TATA box-binding protein-associated factor 1 ( TAF1 ) gene [6]. Forty years after its first description, the natural history of the disorder was characterized, and further epidemiological data continue to be collected in the Philippine XDP Registry [7]. Age at onset is typically in the 4th decade (range 12–64 years), with a mean duration of illness of 16 years and a mean age at death of 55.6 years.…”