Phenotype of five patients with dopa-responsive dystonia and mutations in GCH1

Research output: Contribution to journalResearch articleContributedpeer-review


  • Angela M. Kaindl - , Charité – Universitätsmedizin Berlin, Dresden University of Technology (Author)
  • Daniela Steinberger - , Justus Liebig University Giessen, Bioscientia Ingelheim (Author)
  • Georg Heubner - , Dresden University of Technology (Author)
  • Ulrich Müller - , Justus Liebig University Giessen (Author)
  • Nenad Blau - , University of Zurich (Author)
  • Kerstin Neubert - , Dresden University of Technology (Author)
  • Bernhard Kunath - , Dresden University of Technology (Author)
  • Maja Von Der Hagen - , Department of Paediatrics, Division of Neuropediatrics (Author)


Autosomal dominant dystonia with diurnal variation, also known as DOPA-responsive dystonia (DRD, Segawa syndrome; MIM#128230), can be caused by mutations in the GTP cyclohydrolase 1 gene GCH1 on chromosome 14q22.1-q22.2. Reports on patients with thoroughly characterized DRD phenotypes and GCH1 mutations have disclosed marked phenotypic variability. Here, we report on five patients of two unrelated families with DRD and heterozygous nonsense (c.181G > T) or heterozygous splice site mutations (IVS5 + 3insT) of GCH1. Symptoms reported by these patients include gait abnormality, foot deformity, torticollis, muscle weakness, muscle cramps, myalgia, tremor, depression, and attention deficit. The severity of symptoms varied from mild involvement with good response to levodopa to severe dystonia with marked gait disturbances and only incomplete amelioration of symptoms upon levodopa treatment. The affected parent of each index patient had been misdiagnosed with a psychiatric and/or neurological disorder; the correct diagnosis was assigned only after the diagnosis of DRD had been established in their children. Our report adds further features to the phenotype of DRD caused by GCH1 gene mutations.


Original languageEnglish
Pages (from-to)83-87
Number of pages5
JournalJournal of Pediatric Neurology
Issue number2
Publication statusPublished - 2005

External IDs

Scopus 33751064793



  • Dopa-responsive dystonia, Levodopa, Segawa syndrome