The pathology of FXTAS

In 2002, a syndrome of tremor, ataxia, cognitive decline, and the presence of unique ubiquitin staining intranuclear inclusions in the brain was discovered in premutation males carrying an expansion of between 55 and 200 CGG trinucleotide repeats on the FMR1 gene. This clinical syndrome is now known as fragile X-associated tremor/ataxia (FXTAS) and has been found in both male and female carriers of the expanded premutation allele. The goal of this chapter is to summarize what is known about the anatomical pathology associated with the fragile X premutation and particularly in those individuals with FXTAS. Neuropathology in FXTAS was initially found in the central nervous system, but recent evidence has demonstrated pathological features, including intranuclear inclusions, in the peripheral nervous system, the enteric nervous system, and the neuroendocrine system. The precise cellular dysfunctions that underlie these pathologic features are currently under intense investigation with the goal of prevention and treatment of this devastating disorder.