IllnessDystonia, Dopa-responsive; differential diagnosis

NGS +

[Sanger]

In Dopa-Responsive dystonia (DRD), mild to severe involuntary muscle contractions, tremor and especially dystonia occur. Symptoms of DRD usually begin in childhood, often by age 6. The first signs are typically clubfeet and dystonia in the lower limbs. DRD spreads to the upper limbs, and by adolescence, virtually the entire body is affected. Affected individuals sometimes have unusual limb positions and lack of coordination when walking and running. Some patients have sleep problems or depressive episodes, often parkinsonism. The movement disorder worsens with age, but it stabilizes around age 30. Characteristic is diurnal fluctuation, i.e., worsening of problems during the day and morning betterment after waking. In rare cases, movement problems do not appear until adulthood. GCH1 mutations are the most common cause of DRD, less commonly mutated TH or SPR genes. In some cases, the genetic cause remains unclear. When DRD is caused by mutations in the GCH1 gene, it is inherited in an autosomal dominant manner. Some GCH1 mutation carriers never develop symptoms, but women are 2-4 times more likely to be affected than men. When TH gene mutations are responsible, DRD is inherited in an autosomal recessive manner; when caused by SPR mutations, DRD can be inherited either in an autosomal recessive manner or, less commonly, in a dominant manner. A negative DNA test result does not exclude the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1508/

https://www.ncbi.nlm.nih.gov/books/NBK1437/

https://www.ncbi.nlm.nih.gov/books/NBK304122/

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