Dopa-responsive dystonia or early-onset Parkinson disease - Genotype-phenotype correlation.
OBJECTIVE
Dopa-responsive dystonia (DRD) is a rare form of hereditary movement disorder with onset in childhood, characterized by gait difficulties due to postural dystonia with marked improvement after low doses of levodopa. Mutations in the GCH1 gene are the most common cause of DRD, however, in some cases when the disease is associated with parkinsonism mutations in the PARK2 gene may be identified. The aim of this study was to analyze and compare genotype-phenotype correlation.
Four families with inter- and intrafamilial variability of progressive gait dysfunction due to lower limb dystonia occurring in childhood or adolescence were included in the analysis.


METHODS
General and neurological examination was performed for all affected family members and asymptomatic mutation carriers. The molecular analysis encompassed GCH1 and PARK2 genes.


RESULTS
All probands were clinically diagnosed with DRD. The molecular analysis revealed, however, that the dopa-responsive dystonia phenotype was caused by a mutation in the GCH1 gene in three families and in the PARK2 gene in one family. Obtained results allowed to establish the final diagnosis for all families as DYT5a or early-onset Parkinson disease (EO-PD).


CONCLUSIONS
Reported cases confirm that the DRD phenotype may have heterogeneous genetic background and may be caused by point mutations or rearrangements in the GCH1 gene as well as in the PARK2 gene. Differential diagnosis and genetic tests covering the analysis of genes causative for DRD and EO-PD should be obligatory in both disorders diagnostics as DRD, mainly adolescent onset dystonia, may be associated with parkinsonism.
Department of Neurology, Medical University of Warsaw, Warsaw, Poland. Electronic address: apotulska@wum.edu.pl.
Anna
A
Potulska-Chromik
Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
Dorota
D
Hoffman-Zacharska
Student Scientific Group by the Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
Małgorzata
M
Łukawska
Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
Anna
A
Kostera-Pruszczyk
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D020821:Dystonic Disorders / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D006136:GTP Cyclohydrolase
DYT5; Dopa-responsive dystonia; Early-onset Parkinson disease; GCH1; PARK2