Phenotypic expression of X‐linked dystonia‐parkinsonism (lubag) in two women

Abstract

Lubag (X-linked dystonia-parkinsonism) has been considered a sex-linked recessive trait and has been mapped to the pericentromeric region of the X chromosome. We studied a 54-year-old man with lubag and two of his female first cousins. Genetic typing was carried out using X chromosome markers. Fluorodopa PET was performed on the man and one of the women. The man had moderately severe parkinsonism and dystonia. A 61-year-old female first cousin had mild left-sided dystonia and her 54-year-old sister had mild generalized chorea. Genetic typing data revealed that all three inherited an X chromosome with marker alleles strongly associated with lubag. Cytologic analysis did not reveal evidence of X chromosomal deletion. Fluorodopa PET in both the man and one affected cousin revealed reduced striatal uptake rate constants consistent with nigrostriatal involvement. These observations suggest that lubag may be a codominant disorder and that it is possible for women to be affected.

Rapid-onset dystonia-parkinsonism: Linkage to chromosome 19q13

“…Although it is rare, it has clinical and biochemical similarities to several forms of hereditary dystonia and parkinsonism, as well as genetic and biochemical differences. A major difference is that PD, 38 HJPD, 39 and XDP 40 show marked degeneration of dopaminergic neurons on PET studies, whereas RDP 23 and DRD 29 do not show this. In addition, unlike RDP, individuals with PD develop symptoms gradually, usually in late adulthood, and initially improve with carbidopa/levodopa.…”

Neuropsychological Profile of a Filipino Gentleman with X-Linked Dystonia–Parkinsonism: A Case Report of Lubag Disease

“…Additionally, most surgical interventions such as thalamotomies, pallidotomies, and cerebellar implantation have not yielded promising results (Lee et al, 1976(Lee et al, , 2002Waters et al, 1993b). In June 2007, however, a case report of a 45-year-old male with generalized dystonia and parkinsonism who underwent bilateral pallidal (Gpi) deep brain stimulation (DBS) indicated a 71% improvement in dystonic symptoms and a 68% improvement in parkinsonian symptoms, 1 year post surgery.…”

“…The Filipinos themselves therefore prefer to use the more specific term of XDP or DYT3, rather than the general term of Lubag disease. Of the cases of XDP, 99% are male, although females are carriers of the gene and there can be female cases (Evidente et al, 2004b;Kupke et al, 1990;Lee et al, 2002;Waters et al, 1993b). Reports of women's symptoms are variable, but generally suggest a less severe course than in males.…”

“…Reports of women's symptoms are variable, but generally suggest a less severe course than in males. In some cases, females exhibit mild dystonia and non-progressive chorea or other mild non-disabling symptoms, whereas other female patients deteriorate slowly and require medication intervention (Evidente et al, 2004b;Lee et al, 2002;Waters et al, 1993b). Lee and colleagues (2002) thoroughly investigated 376 cases of XDP registered with the Philippine XDP project.…”

Rare Causes of Dystonia Parkinsonism

“…Mean age of onset is around 30 years. All 28 cases of an early series were male and inheritance was compatible with an X-linked recessive trait [76], but females may also be affected, albeit mostly mildly [79,80].…”