"The FMR1 premutation occurs in approximately 1/800 males and 1/250 females 1. Penetrance of FXTAS is age-dependent, affecting 40-45% of male and 8-16% of female premutation carriers (PMC) over the age of 50 years2."
"Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive degenerative movement disorder resulting from a fragile X “premutation”, defined as 55-200 CGG repeats in the 5’-untranslated region of the FMR1 gene 1. The premutation can expand in subsequent generations (during oogenesis) to a full mutation causing fragile X syndrome."
"The FMR1 premutation occurs in approximately 1/800 males and 1/250 females 1. Penetrance of FXTAS is age-dependent, affecting 40-45% of male and 8-16% of female premutation carriers (PMC) over the age of 50 years2."
"The pathogenesis of FXTAS is not yet fully understood 2. Neuronal toxicity in FXTAS is thought to result from the formation of pathognomonic eosinophilic and ubiquitin-positive intranuclear inclusions in neurones and astrocytes in the cerebrum, thalamus, basal ganglia and inferior olivary, dentate and hypoglossal nuclei, as well as in the spinal cord and autonomic ganglia."
"The pathogenesis of FXTAS is not yet fully understood 2. Neuronal toxicity in FXTAS is thought to result from the formation of pathognomonic eosinophilic and ubiquitin-positive intranuclear inclusions in neurones and astrocytes in the cerebrum, thalamus, basal ganglia and inferior olivary, dentate and hypoglossal nuclei, as well as in the spinal cord and autonomic ganglia."
"The revised FXTAS diagnostic criteria include two major radiological features 3:"
"the best-recognised feature of FXTAS is the MCP sign, which refers to T2 hyperintensity in the middle cerebellar peduncles, and is present in 60% of affected males and 13% of affected females 4"
"T2 hyperintensity in the afferent projections of the middle and superior cerebellar peduncles has been reported in asymptomatic premutation carriers and may be the earliest neuroanatomical marker heralding the onset of FXTAS 3"
"marked reduction of fractional anisotropy in the middle and superior cerebellar peduncles, cerebral peduncles, fornix and stria terminalis in male premutation carriers with FXTAS"
"The rate of progression of FXTAS is variable, and life expectancy ranges from 5 to 25 years following the onset of symptoms 2. The presence of the MCP sign in patients with FXTAS is correlated with more severe cognitive deficits and a long history of symptoms 2. There are no disease-modifying treatments for FXTAS."
"The rate of progression of FXTAS is variable, and life expectancy ranges from 5 to 25 years following the onset of symptoms 2. The presence of the MCP sign in patients with FXTAS is correlated with more severe cognitive deficits and a long history of symptoms 2. There are no disease-modifying treatments for FXTAS."
"The rate of progression of FXTAS is variable, and life expectancy ranges from 5 to 25 years following the onset of symptoms 2. The presence of the MCP sign in patients with FXTAS is correlated with more severe cognitive deficits and a long history of symptoms 2. There are no disease-modifying treatments for FXTAS."
"Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive degenerative movement disorder resulting from a fragile X “premutation”, defined as 55-200 CGG repeats in the 5’-untranslated region of the FMR1 gene 1. The premutation can expand in subsequent generations (during oogenesis) to a full mutation causing fragile X syndrome."
"The FMR1 premutation occurs in approximately 1/800 males and 1/250 females 1. Penetrance of FXTAS is age-dependent, affecting 40-45% of male and 8-16% of female premutation carriers (PMC) over the age of 50 years2."
"Neurodegeneration in the cerebellum is characterised by marked Purkinje cell loss, gliosis and axonal swelling. Furthermore, elevated FMR1 mRNA levels seen in premutation carriers have been implicated by way of a neurotoxic gain of function effect."
Expected headings
"Clinical features"
"Radiological features"
"definite: one major clinical and one major radiological; or one major clinical and intranuclear inclusions"
"probable: two major clinical; or one minor clinical and one major radiological"
"The classical presentation is a kinetic tremor and cerebellar ataxia occurring over the age of 50 years 1. Other clinical manifestations include cognitive decline and dementia, parkinsonism, psychiatric disorders, sensorineural hearing loss, peripheral sensory neuropathy, and autonomic dysfunction (e.g. erectile dysfunction, orthostatic hypotension) 2,8. Affected females typically experience less severe disease."
"The pathogenesis of FXTAS is not yet fully understood 2. Neuronal toxicity in FXTAS is thought to result from the formation of pathognomonic eosinophilic and ubiquitin-positive intranuclear inclusions in neurones and astrocytes in the cerebrum, thalamus, basal ganglia and inferior olivary, dentate and hypoglossal nuclei, as well as in the spinal cord and autonomic ganglia."
"Neurodegeneration in the cerebellum is characterised by marked Purkinje cell loss, gliosis and axonal swelling. Furthermore, elevated FMR1 mRNA levels seen in premutation carriers have been implicated by way of a neurotoxic gain of function effect."
"The adrenals, thyroid, Leydig cells, pancreas, gastrointestinal tract, kidneys and heart are also involved."
"white matter T2 hyperintensities in the pons, insula and periventricular region 2"
"marked reduction of fractional anisotropy in the middle and superior cerebellar peduncles, cerebral peduncles, fornix and stria terminalis in male premutation carriers with FXTAS"
"The rate of progression of FXTAS is variable, and life expectancy ranges from 5 to 25 years following the onset of symptoms 2. The presence of the MCP sign in patients with FXTAS is correlated with more severe cognitive deficits and a long history of symptoms 2. There are no disease-modifying treatments for FXTAS."