Movement Disorders Center @ MMC

X-linked Dystonia Parkinsonism (XDP)

X-linked dystonia parkinsonism (XDP, DYT3) is an adult-onset sex-linked neurodegenerative movement disorder with features of both dystonia and parkinsonism. It is endemic to the Panay Island in the Philippines and all cases are linked to Filipino ancestry.

History

Sex-linked recessive dystonia parkinsonism (XDP) is a movement disorder first reported in 1975 on patients from the island of Panay, Philippines. Dr George H. Viterbo, of Roxas City, Capiz (a province of Panay) referred to the neurology section of the Philippine General Hospital in the early 1970s, five of the six cases of what then was rare ‘dystonia musculorum deformans’. This initiated an epidemiologic survey, which resulted in the first paper published in 1976. In the original paper, Lee et al. described 28 adult male cases with torsion dystonia, from 25 families. There was no male to male transmission hence, the inference of sex-linked recessive transmission. Some of the patients were noted to have parkinsonian features and some had relatives with parkinsonism.

 
Lee and colleagues described the phenotype of the disease as a combination of dystonia and parkinsonism (K. G. Kupke et al., 1990; Lillian V. Lee et al., 1991) which was confirmed by Fahn and co-workers (Wilhelmsen et al., 1991). ]. Fahn called the disease ‘lubag’ based on the term used by the Ilongo speaking Filipinos to describe any movement characterized by torsion including children with cerebral palsy. The phenomenology of the disease was further elucidated in a 2001-2002 review (L. V. Lee et al., 2001; Lillian V. Lee et al., 2002).

Clinical Manifestation

Most patients cite dystonia as the precipitating symptom for consult. The most prominent symptom of XDP, and the one most initially noticeable to the individual, is focal dystonia, in the neck, jaw, or limb, or as blepharospasm. There is progression to regional or generalized dystonia over time, but progression rate is highly variable. Regardless of the first site of regional involvement, the initial focal dystonia in XDP spreads 97% of the time and generalizes within 5 years in 84% (Lee et al., 2011a). This dystonic phase may also be milder in females, but can be fully expressed in both sexes.


Over time, an average of 7 to 10 years from time of diagnosis, there is gradual amelioration of the severity of the dystonia and progression of parkinsonian symptoms. By the 15th year from the initial dystonic symptoms, the predominant picture is one of parkinsonism manifesting as tremors, bradykinesia, and masked facies (Rosales, 2010).