Objective: The authors reviewed the pathophysiology, clinical genetics, phenotype, and comprehensive clinical management of Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), a neurodegenerative disorder affecting FMR1 premutation carriers (55–200 CCG repeats). Participants: A multispecialty and multidisciplinary team of authors with backgrounds in psychiatry, pediatrics, clinical psychology, speech and language pathology, and neurosciences. Evidence: Review of English language sources on the clinical phenomenology, genetics, pathophysiology, and clinical management of FXTAS from 2001 (the original report) through 2025, with emphasis on the general medical, psychiatric, and neurological features of FXTAS and its multispecialty and multidisciplinary clinical management. Consensus process: All authors contributed to the review of the literature. Major components of the manuscript were drafted by clinicians with clinical experience in the specific areas of management. Conclusion: Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a neurodegenerative disorder affecting FMR1 premutation carriers (55–200 CCG repeats) that is an illustrative model for a genetically-determined neuropsychiatric illness. It is characterized by intention tremor, gait ataxia, neurocognitive disorder, and other psychiatric symptoms. FXTAS occurs in patients with a family history of Fragile X-associated conditions, including Fragile X syndrome. Patients often develop fronto-subcortical dementia/major neurocognitive disorder (MNCD), leading to significant functional decline (particularly in males). A holistic, person-centered approach coordinated by the primary care clinician with multispecialty and multidisciplinary collaboration is recommended to address the complex needs of FXTAS patients and their support networks. This highlights the importance of integrated support for patients and caregivers, including addressing end-of-life/palliative care considerations.
Bourgeois et al. (Wed,) studied this question.