Di Lazzaro, G;
Magrinelli, F;
Estevez-Fraga, C;
Valente, EM;
Pisani, A;
Bhatia, KP;
(2021)
X-Linked Parkinsonism: Phenotypic and Genetic Heterogeneity.
Movement Disorders
10.1002/mds.28565.
(In press).
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Abstract
X-linked parkinsonism encompasses rare heterogeneous disorders mainly inherited as a recessive trait, therefore being more prevalent in males. Recent developments have revealed a complex underlying panorama, including a spectrum of disorders in which parkinsonism is variably associated with additional neurological and non-neurological signs. In particular, a childhood-onset encephalopathy with epilepsy and/or cognitive disability is the most common feature. Their genetic basis is also heterogeneous, with many causative genes and different mutation types ranging from "classical" coding variants to intronic repeat expansions. In this review, we provide an updated overview of the phenotypic and genetic spectrum of the most relevant X-linked parkinsonian syndromes, namely X-linked dystonia-parkinsonism (XDP, Lubag disease), fragile X-associated tremor/ataxia syndrome (FXTAS), beta-propeller protein-associated neurodegeneration (BPAN, NBIA/PARK-WDR45), Fabry disease, Waisman syndrome, methyl CpG-binding protein 2 (MeCP2) spectrum disorder, phosphoglycerate kinase-1 deficiency syndrome (PGK1) and X-linked parkinsonism and spasticity (XPDS). All clinical and radiological features reported in the literature have been reviewed. Epilepsy occasionally represents the symptom of onset, predating parkinsonism even by a few years; action tremor is another common feature along with akinetic-rigid parkinsonism. A focus on the genetic background and its pathophysiological implications is provided. The pathogenesis of these disorders ranges from well-defined metabolic alterations (PGK1) to non-specific lysosomal dysfunctions (XPDS) and vesicular trafficking alterations (Waisman syndrome). However, in other cases it still remains poorly defined. Recognition of the phenotypic and genetic heterogeneity of X-linked parkinsonism has important implications for diagnosis, management, and genetic counseling. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
| Type: | Article |
|---|---|
| Title: | X-Linked Parkinsonism: Phenotypic and Genetic Heterogeneity. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/mds.28565 |
| Publisher version: | https://doi.org/10.1002/mds.28565 |
| Language: | English |
| Additional information: | © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | BPAN, FXTAS, MeCP2, X-linked parkinsonism, XDP |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10127708 |
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