X-linked Parkinsonism is a rare inherited disorder that mainly affects males. It has been observed that the condition is also linked to other non-neurological signs. The most prevalent trait is a childhood-onset encephalopathy with epilepsy and/or cognitive impairment. Their genetic foundation is equally diverse, with a variety of causal genes and mutation types ranging from “traditional” coding variations to intronic repeat expansions. Researchers provided an updated overview of the phenotypic and genetic spectrum of the most relevant X-linked parkinsonian syndromes, including 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 (XPDS). Every clinical and radiological characteristic that has been described in the literature was examined.
A special emphasis was placed on the genetic basis and its pathophysiological consequences. The pathogenesis of these disorders ranged from well-defined metabolic alterations (PGK1) to non-specific lysosomal dysfunctions (XPDS) and abnormalities in vesicular trafficking (Waisman syndrome). In certain circumstances, however, it is still inadequately defined. The fact that X-linked Parkinsonism has clinical and genetic variation has crucial implications for diagnosis, treatment, and genetic counseling.
Reference:movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28565
