Autosomal dominant dopa-responsive parkinsonism in a multigenerational Swiss family

Wider, C.; Skipper, L.; Solida, A.; Brown, L.; Farrer, M.; Dickson, D.; Wszolek, Z.K.; Vingerhoets, F.J.G.

doi:10.1016/j.parkreldis.2007.11.013

« Previous Next »Parkinsonism & Related Disorders
Volume 14, Issue 6 , Pages 465-470, August 2008

Autosomal dominant dopa-responsive parkinsonism in a multigenerational Swiss family

C. Wider
- Department of Neurology, CHUV, Lausanne, Switzerland
- Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
L. Skipper
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
A. Solida
- Department of Neurology, CHUV, Lausanne, Switzerland
L. Brown
- Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
M. Farrer
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
D. Dickson
- Department of Neuropathology, Mayo Clinic, Jacksonville, FL, USA
Z.K. Wszolek
- Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
F.J.G. Vingerhoets
- Department of Neurology, CHUV, Lausanne, Switzerland
- Corresponding author. Service de Neurologie, CHUV BH 13, Rue du Bugnon, 1011 Lausanne, Switzerland. Tel.: +41 21 314 1232; fax: +41 21 314 1287.

Received 25 August 2007; received in revised form 27 October 2007; accepted 7 November 2007.

Abstract

Aim

To describe a large family with autosomal dominant parkinsonism.

Background

Seven genes are directly implicated in autosomally inherited parkinsonism. However, there are several multigenerational large families known with no identifiable mutation.

Material and methods

Family members were evaluated clinically, by history and chart review. Genetic investigation included SCA2, SCA3, UCHL1, SNCA, LRRK2, PINK1, PRKN, PGRN, FMR1 premutation, and MAPT. The proband underwent brain fluorodopa PET (FD-PET) scan, and one autopsy was available.

Results

Eleven patients had a diagnosis of Parkinson's disease (PD), nine women. Mean age of onset was 52 with tremor-predominant dopa-responsive parkinsonism. Disease progression was slow but severe motor fluctuations occurred. One patient required subthalamic nucleus deep-brain stimulation with a good motor outcome. One patient had mental retardation, schizophrenia and became demented, and another patient was demented. Three patients and also two unaffected subjects had mild learning difficulties. All genetic tests yielded negative results. FD-PET showed marked asymmetric striatal tracer uptake deficiency, consistent with PD. Pathological examination demonstrated no Lewy bodies and immunostaining was negative for α-synuclein.

Conclusion

Apart from a younger age of onset and a female predominance, the phenotype was indistinguishable from sporadic tremor-predominant PD, including FD-PET scan results. As known genetic causes of autosomal dominant PD were excluded, this family harbors a novel genetic defect.

Keywords: Familial, Autosomal dominant, Parkinsonism, Parkinson's disease