open access

Vol 51, No 1 (2017)
Original research articles
Submitted: 2016-05-07
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Dopa-responsive dystonia or early-onset Parkinson disease – Genotype–phenotype correlation

Anna Potulska-Chromik, Dorota Hoffman-Zacharska, Małgorzata Łukawska, Anna Kostera-Pruszczyk
DOI: 10.1016/j.pjnns.2016.07.013
·
Neurol Neurochir Pol 2017;51(1):1-6.

open access

Vol 51, No 1 (2017)
Original research articles
Submitted: 2016-05-07

Abstract

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.

Material/participants

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.

Abstract

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.

Material/participants

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.

Get Citation

Keywords

Dopa-responsive dystonia, DYT5, Early-onset Parkinson disease, GCH1, PARK2

About this article
Title

Dopa-responsive dystonia or early-onset Parkinson disease – Genotype–phenotype correlation

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 51, No 1 (2017)

Pages

1-6

DOI

10.1016/j.pjnns.2016.07.013

Bibliographic record

Neurol Neurochir Pol 2017;51(1):1-6.

Keywords

Dopa-responsive dystonia
DYT5
Early-onset Parkinson disease
GCH1
PARK2

Authors

Anna Potulska-Chromik
Dorota Hoffman-Zacharska
Małgorzata Łukawska
Anna Kostera-Pruszczyk

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