Since the original description of FXTAS, there have been many reports and series describing phenotypic differences between males and females. In males, FXTAS is usually characterized by progressive tremor and gait ataxia. Other common features are parkinsonism, peripheral neuropathy, hypertension, autonomic dysfunction, anxiety, and depression. Cognitive decline is a highly prevalent and disabling symptom. Brain MRI usually shows atrophy of the cerebrum, cerebellar cortex, corpus callosum and pons, and white matter increased T2 signal intensity. The MCP sign (middle cerebellar peduncles hyperintense signal in T2) is observed in approximately 60% of the cases.[1, 2, 4] In contrast, in females with FXTAS, tremor is rarely the initial presentation and is usually a later feature (prevalence of tremor range: 12%–75%) and ataxia is typically milder than in males. As in males, the neurophysiological characteristics of tremor in women with FXTAS have not been well studied. In addition, there are few detailed descriptions of the clinical features of tremor in FXTAS. Parkinsonism can be prominent as the disease progresses. Cognitive impairment is less commonly reported and leads to minor disability. Depression is a common feature (approximately 40%), and, interestingly, it was suggested that women with FXTAS show predisposition to psychogenic disorders. In female premutation carriers, primary ovarian dysfunction (20%), sensory loss (45%), chronic pain (26%), thyroid disorders (50%), and fibromyalgia are also common features. MRI studies showed MCP in only 13% of females.[1-5]
In our patient, the clinical presentation with a slowly progressive intention tremor and mild gait disturbance could potentially lead to the misdiagnosis of essential tremor. The early development of mild ataxia (rather than later onset that may be more common in essential tremor) was a clue to the diagnosis. In her case, the family history of Fragile X syndrome also clearly oriented the diagnosis; however, FXTAS should also be considered in the absence of a family history of mental retardation, autism, or learning disorders.