Download PDF
Journal of Pediatric Neurology 2005; 03(02): 083-087
DOI: 10.1055/s-0035-1557248
Original Article
Georg Thieme Verlag KG Stuttgart – New York

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

Angela M. Kaindl
a   Department of Neuropediatrics, Children’s Hospital, Technical University Dresden, Germany
b   Department of Neuropediatrics, Charité, University Medical School Berlin, Germany
,
Daniela Steinberger
c   Institute of Human Genetics, University of Giessen, Germany
d   Center for Human Genetics, Bioscientia Ingelheim, Germany
,
Georg Heubner
a   Department of Neuropediatrics, Children’s Hospital, Technical University Dresden, Germany
,
Ulrich Müller
c   Institute of Human Genetics, University of Giessen, Germany
,
Nenad Blau
e   Division of Clinical Chemistry and Biochemistry, University Children’s Hospital, Zurich, Switzerland
,
Kerstin Neubert
a   Department of Neuropediatrics, Children’s Hospital, Technical University Dresden, Germany
,
Bernhard Kunath
f   Department of Neurology, Technical University Dresden, Germany
,
Maja von der Hagen
a   Department of Neuropediatrics, Children’s Hospital, Technical University Dresden, Germany
› Author Affiliations
Subject Editor:
Further Information

Publication History

20 July 2004

21 October 2004

Publication Date:
29 July 2015 (online)

Also available at
  PDF Download  Permissions and Reprints

Abstract

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 I 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.

Keywords

Dopa-responsive dystonia - Segawa syndrome - levodopa