Clinical Guidance

All symptomatic individuals have the same disease-associated TAF1/DYT3 haplotype regardless of phenotype , which comprises a spectrum including pure parkinsonism, focal dystonia, segmental dystonia, multifocal dystonia, and generalized dystonia in symptomatic men and chorea, pure parkinsonism, and focal or multifocal dystonia in symptomatic women. Recently, have further analyzed the sequence of the SVA in TAF1 and detected polymorphic variation in the length of a hexanucleotide repeat domain, (CCCTCT)n, which varies from 35 to 52 repeats. The length of the repeat correlates inversely with age at disease onset .

Source: GeneReviews — "X-Linked Dystonia-Parkinsonism"

Diagnostic Criteria

Clinical Diagnosis

The diagnosis of X-linked dystonia-parkinsonism (XDP) should be suspected in an individual with the following clinical findings, neuroimaging results, and neurophysiologic test results.

Clinical findings

• Dystonia of varying severity, ranging from focal to generalized typically starting in early adulthood

• Parkinsonism

• Family history consistent with X-linked inheritance

• Maternal ancestral roots from the Panay Islands in the Philippines where XDP originated as a genetic founder effect. All known affected individuals to date are of Filipino descent.

Source: GeneReviews — "X-Linked Dystonia-Parkinsonism"

Differential Diagnosis

See Dystonia Overview. Individuals with X-linked dystonia-parkinsonism (XDP) with tremor can be misdiagnosed as having Parkinson disease or essential tremor, especially in the early stages in which dystonia may be absent or subtle. Individuals with XDP with all the cardinal features of parkinsonism, asymmetric findings, and levodopa responsiveness are often diagnosed as having Parkinson disease or Parkinson-plus syndrome.

Source: GeneReviews — "X-Linked Dystonia-Parkinsonism"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with X-linked dystonia-parkinsonism (XDP) syndrome, the following evaluations are recommended if they have not already been completed:

• Neurologic examination

• Assessment of speech

• Assessment of swallowing

• Nutritional assessment

• Surface electromyography study

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Pharmacologic Treatment of Dystonia

Anticholinergic agents and benzodiazepines. In the early stages of the disease when dystonia is focal or segmental in distribution, individuals may respond significantly to anti-dystonia medications, particularly to anticholinergic agents and benzodiazepines.

• The two most commonly prescribed anticholinergic drugs are trihexyphenidyl (Artane) and biperiden (Akineton). Trihexyphenidyl appears to have a more consistent and beneficial effect than biperiden, especially in the moderate-to-advanced stages.

• The benzodiazepine associated with the best response is clonazepam.

• Even greater improvement in dystonia is noted when anticholinergic drugs are combined with clonazepam.

Source: GeneReviews — "X-Linked Dystonia-Parkinsonism"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "X-Linked Dystonia-Parkinsonism"

Surveillance Guidelines

Presymptomatic males known to have the disease-associated haplotype may need yearly clinical evaluations after age 30 years to identify the onset of symptoms in order to institute appropriate therapy as early as possible. Once an individual is symptomatic, biannual follow ups are recommended in order to adjust medications to assure best management of dystonia and/or parkinsonism. Periodic swallowing evaluation, especially in those with subjective dysphagia, is appropriate.

Source: GeneReviews — "X-Linked Dystonia-Parkinsonism"