The imperative for multigenerational genetic screening: A case report of fragile X-associated tremor/ataxia syndrome (FXTAS).

RATIONALE: Fragile X-associated tremor/ataxia syndrome (FXTAS), presenting with cognitive impairment as the initial symptom, is rare. This report emphasizes the need to consider FXTAS diagnosis in cases of early onset cognitive impairment in an aging population.

PATIENT CONCERNS: A 57-year-old male with FXTAS was initially misdiagnosed with neuronal intranuclear inclusion disease, whose first manifestation was cognitive impairment. Testing showed a verbal IQ of 74, a performance IQ of 73, and a full scale of IQ 71, and a Clinical Memory Quotient of 74. Furthermore, his Mini-Mental State Examination score of 23 reflected a decline in short-term memory. Following reevaluation of imaging, identified T2-fluid attenuation inversion recovery hyperintensity at the cerebellar peduncles, and further investigation of the family history revealing a 7-year-old grandson with fragile X syndrome (FXS), repeat genetic testing of the patient demonstrated 121 CGG repeats in the FMR1 gene, confirming the diagnosis of FXTAS.

DIAGNOSES: FXTAS.

INTERVENTIONS: The patient was treated with donepezil and simvastatin daily and alcohol consumption was restricted.

OUTCOMES: After 1 year, the patient showed partial improvements in memory, with his Mini-Mental State Examination score rising to 27, allowing him to resume employment as a community security guard.

LESSONS: Due to the highly variable clinical presentation of FXS within families, clinicians should always consider fragile X testing and detailed family history when middle-aged and elderly males exhibit unexplained cognitive impairment or tremors. With the acceleration of aging in society, this case underscores the importance of multigenerational genetic screening for maternal grandparents, particularly males, in FXS families and prioritizing follow-up monitoring.