Fragile X-associated tremor/ataxia syndrome

Niranjan N Singh MD (Dr. Singh of the University of Missouri - Columbia has no relevant financial relationships to disclose.)
Florian P Thomas MD MA PhD MS (

Dr. Thomas of Hackensack University Medical Center, Hackensack Meridian School of Medicine at Seton Hall University, has no relevant financial relationships to disclose.

Joseph Jankovic MD, editor. (

Dr. Jankovic, Director of the Parkinson's Disease Center and Movement Disorders Clinic at Baylor College of Medicine, received research and training funding from Allergan, F Hoffmann-La Roche, Medtronic Neuromodulation, Merz, Neurocrine  Biosciences, Nuvelution, Revance, and Teva and consulting/advisory board honorariums from Abide, Lundbeck, Retrophin, Parexel, Teva, and Allergan.

Originally released September 25, 2004; last updated March 2, 2020; expires March 2, 2023

This article includes discussion of Fragile X-associated tremor/ataxia syndrome and FXTAS. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset triplet repeat disorder that leads to dementia, ataxia, tremor, and neuropathy. Its cause is a restricted triplet repeat expansion mutation in the fragile X mental retardation gene (FMR1), whereas a larger expansion results in fragile X syndrome A in children. Fragile X-associated tremor/ataxia syndrome affects less than 20% of female and about 50% of male carriers. In this article, the authors focus on fragile X-associated tremor/ataxia syndrome and its relation to fragile X syndrome A. Fragile X-associated tremor/ataxia syndrome illustrates the importance of obtaining a comprehensive family history that is not limited to clinical question of the patient in question. Fragile X-associated tremor/ataxia syndrome is in the differential diagnosis in patients with various combinations of the above symptoms with or without a family history of mental retardation. Some estimates suggest that as many as one in 3000 men above 50 years of age may develop fragile X-associated tremor/ataxia syndrome; such numbers would signify a great impact on healthcare costs. The pathomechanistic evidence of mitochondrial and RNA dysfunction and of a neurodevelopmental component to fragile X-associated tremor/ataxia syndrome is discussed.

Historical note and terminology

Researchers first began to look for a connection between fragile X syndrome A and the neurologic symptoms in elderly men when mothers of affected children noted that their children s grandfathers became forgetful, had frequent falls, and other neurologic problems. This resulted in the recognition of a syndrome originally referred to as “intention tremor, parkinsonism, and generalized brain atrophy in male carriers of a fragile X premutation” (Hagerman et al 2001).

In fragile X syndrome A, a cytosine-guanine-guanine (CGG) triplet repeat expansion in excess of 200 repeats leads to silencing of the FMR1 gene and its protein product, fragile X mental retardation protein, whereas fragile X-associated tremor/ataxia syndrome patients have a triplet repeat expansion of 55 to 200 CGG repeats.

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