1. Background

• also called Segawa Disease
• the Dopa-Responsive Dystonia (DRD) gene has been mapped to chromosome 14q (Nygaard et al., Nature Genetics 5:386-391, 1993)
• all three forms of inherited dystonia have had their disease locus genetically mapped
  • Idiopathic Torsion Dystonia - 9q32-34
  • Dopa-Responsive Dystonia - 14q
  • X-linked Dystonia-Parkinsonism - Xq21

2. Genetic Defect

• genetic defect -> deficiency of striatal dopamine -> dystonia with parkinsonian features
• the DRD gene may be responsible for the normal development or maintenance of the striatal dopaminergic system and a defect in the gene may result in a:
  • reduced number of dopaminergic nerve terminals occurring during development
  • excessive reduction (pruning) of these terminals occurring during post-natal development

1. Dystonic Manifestations

• see "Dystonic Disorders"
• usually presents as a gait disturbance with leg dystonia
• diurnal fluctuations
  • gait disturbance or abnormal lower extremity posture tend to occur late in the afternoon
• dystonia exacerbated by movement and exercise
• associated with parkinsonian features
  • cogwheel rigidity, masklike facies, and bradykinesia
• associated with postural or intention tremor in 50% of patients
• may find family history of dopa-responsive dystonia, variable degrees if dystonia, and parkinsonism

1. Serum

• low biopterin levels (a cofactor for tyrosine hydroxylase - the rate limiting step in dopamine production)

2. Cerebral Spinal Fluid

• reduced levels of homovanillic acid (a dopamine metabolite)

3. Imaging Studies