OBJECTIVE: We delineate the clinical, neurophysiologic and morphologic characteristics of Fragile X-associated Tremor Ataxia Syndrome (FXTAS). BACKGROUND: FXTAS is defined by FMR1 premutation, cerebellar ataxia, intentional tremor and middle cerebellar peduncle (MCP) hyperintensities. DESIGN/METHODS: Description of a multicentric series. Clinical, morphologic (brain MRI, 123I-ioflupane SPECT) and neurophysiologic (tremor recording, nerve conduction studies) study in 22 patients with FXTAS including 4 women. RESULTS: A total of 43% of patients had no family history of fragile X syndrome (FXS) which contrasts with previous FXTAS series. A total of 86% of patients had tremor and 81% peripheral neuropathy. We identified 3 electroclinical tremor patterns: essential-like (35%), cerebellar (29%) and parkinsonian (12%). Two electrophysiologic patterns evocative of non-length-dependent (56%) and length-dependent sensory neuropathy (25%) were identified. Corpus callosum splenium (CCS) hyperintensity was as frequent (68%) as MCP hyperintensities (64%). Sixty percent of patients had parkinsonism and 47% abnormal 123I-ioflupane SPECT. Unified Parkinson9s disease rating scale motor score was correlated to abnormal 123I-ioflupane SPECT (p=0.02) and to CGG repeat number (p=0.0004). Scale for the assessment and rating of ataxia correlated with dentate nuclei hyperintensities (p=0.03) and CCS hyperintensity was a marker of severe disease progression (p=0.04). CONCLUSIONS: We recommend to include in the FXTAS testing guidelines both CCS hyperintensity and peripheral neuropathy and to consider them as new major radiologic and minor clinical criterion, respectively, for the diagnosis of FXTAS. FXTAS should also be considered in women or when tremor, MCP hyperintensities or family history of FXS are lacking. Our study broadens the spectrum of tremor, peripheral neuropathy and MRI abnormalities in FXTAS, hence reveals the need for revised criteria. Disclosure: Dr. Anheim has nothing to disclose. Dr. Apartis has nothing to disclose. Dr. Blancher has nothing to disclose. Dr. Meissner has nothing to disclose. Dr. Maltete has nothing to disclose. Dr. Guyant-Marchal has nothing to disclose. Dr. Thobois has nothing to disclose. Dr. De Broucker has nothing to disclose. Dr. Pollak has nothing to disclose. Dr. Durr has received personal compensation for activities with Pfizer, Inc. Dr. Vidailhet has nothing to disclose. Dr. Brice has nothing to disclose.