Affiliations: Department of Neuropediatrics, Children's Hospital,
Technical University Dresden, Germany | Department of Neuropediatrics, Charité,
University Medical School Berlin, Germany | Institute of Human Genetics, University of Giessen,
Germany | Center for Human Genetics, Bioscientia Ingelheim,
Germany | Division of Clinical Chemistry and Biochemistry,
University Children's Hospital, Zurich, Switzerland | Department of Neurology, Technical University Dresden,
Germany
Note: [] Correspondence: Dr. Angela M. Kaindl, Department of
Neuropediatrics, Children's Hospital, Technical University Dresden,
Fetscherstr. 74, 01307 Dresden, Germany. Tel./Fax: +49 30 450 56 61 12/56 69
20; E-mail: [email protected]
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.
