X?Linked Parkinsonism: Phenotypic and Genetic Heterogeneity

X-linked parkinsonism encompasses rare heterogeneous disorders mainly inherited as a recessive trait, therefore being more prevalent in males. Recent developments have revealed complex underlying panorama, including spectrum of which is variably associated with additional neurological and non-neurological signs. In particular, childhood-onset encephalopathy epilepsy and/or cognitive disability the most common feature. Their genetic basis also heterogeneous, many causative genes different mutation types ranging from “classical” coding variants to intronic repeat expansions. this review, we provide an updated overview phenotypic relevant parkinsonian syndromes, namely 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) disorder, phosphoglycerate kinase-1 deficiency (PGK1) spasticity (XPDS). All clinical radiological features reported literature been reviewed. Epilepsy occasionally represents symptom onset, predating even by few years; action tremor another feature along akinetic-rigid parkinsonism. A focus on background its pathophysiological implications provided. The pathogenesis these ranges well-defined metabolic alterations non-specific lysosomal dysfunctions (XPDS) vesicular trafficking (Waisman syndrome). However, other cases it still remains poorly defined. Recognition heterogeneity has important for diagnosis, management, counseling. © 2021 Authors. Movement Disorders published Wiley Periodicals LLC behalf International Parkinson Disorder Society