Report FXTAS case with optic atrophy, nystagmus, and diagnostic challenges.

Fragile X syndrome (FXS) is a leading cause of inherited intellectual disability and autism, caused by a CGG repeat expansion in the FMR1 gene. While FXS primarily affects individuals with a full mutation (>200 CGG repeats), Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder seen in male carriers of the FMR1 premutation (55-200 CGG repeats). FXTAS is characterized by tremors, ataxia, cognitive decline, and ocular findings such as nystagmus.

A 61-year-old right-handed man with hypertension, diabetes, dyslipidemia, coronary artery disease and essential tremor presented with worsening bilateral blurry vision particularly while driving. Examination revealed symmetric horizontal gaze-evoked nystagmus, bitemporal pallor of optic discs, intention tremors in both hands, mild ataxic gait, and cognitive impairment (MoCA 19/30). Brain MRI showed extensive T2/FLAIR signal abnormalities in bilateral middle cerebellar peduncles and subcortical white matter. A comprehensive laboratory workup for nutritional, metabolic, and paraneoplastic causes of his optic atrophy was unremarkable.  The patient’s clinical manifestations of tremor, ataxic gait, cognitive impairment, and MRI abnormalities in bilateral cerebellar peduncles, together with a family history of developmental delay in one of his grandsons, resulted in suspicion of FXTAS, which was confirmed by genetic test with FMR1 premutation (99 CGG repeats).  

This case highlights several challenges: broad neurological and ocular symptoms required extensive testing, and neuroimaging findings necessitated ruling out systemic, metabolic, and paraneoplastic causes before genetic evaluation. The absence of family history delayed FMR1 testing, and FXTAS was misdiagnosed as essential tremor. The patient's "essential tremor" history and age of onset align with typical FXTAS patterns, making early diagnosis crucial for effective management and counseling. Notably, this case presented bitemporal optic atrophy, a previously unreported finding in FXTAS.