McLeod syndrome is an X-linked neuroacanthocytosis syndrome caused by mutations of the XK gene. Central nervous system manifestations resemble Huntington’s disease, and include a choreatic movement disorder, dysexecutive cognitive deficits, psychiatric abnormalities, and generalized seizures. Neuromuscular manifestations include myopathy, sensory-motor axonal neuropathy, and cardiomyopathy. In the recent years, McLeod syndrome has increasingly recognized in various countries. Several studies demonstrate a high phenotypic variability. Most mutations in the XK gene predict an absent or truncated XK protein, and no clear genotype—genotype correlation has been found. Missense mutations are rare and may be associated with a milder phenotype. Imaging studies demonstrate striatal atrophy and subtle cerebral metabolic abnormalities. Neuropathological studies reveal striatal neuronal loss and gliosis without specific features. There is an ongoing search for a suitable animal model to disclose the pathogenetic mechanisms of the disorder and search for possible therapeutic targets.
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