FXTAS: new insights and the need for revised diagnostic criteria.
OBJECTIVE
Fragile X-associated tremor ataxia syndrome (FXTAS) is defined by FMR1 premutation, cerebellar ataxia, intentional tremor, and middle cerebellar peduncle (MCP) hyperintensities. We delineate the clinical, neurophysiologic, and morphologic characteristics of FXTAS.


METHODS
Clinical, morphologic (brain MRI, (123)I-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 (123)I-ioflupane SPECT. Unified Parkinson's Disease Rating Scale motor score was correlated to abnormal (123)I-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 revealing the need for revised criteria.
AP-HP, Paris, France.
Emmanuelle
E
Apartis
Anne
A
Blancher
Wassilios G
WG
Meissner
Lucie
L
Guyant-Maréchal
David
D
Maltête
Thomas
T
De Broucker
André-Pierre
AP
Legrand
Hichem
H
Bouzenada
Hung Tran
HT
Thanh
Magali
M
Sallansonnet-Froment
Adrien
A
Wang
François
F
Tison
Carole
C
Roué-Jagot
Frédéric
F
Sedel
Perrine
P
Charles
Sandra
S
Whalen
Delphine
D
Héron
Stéphane
S
Thobois
Alice
A
Poisson
Gaetan
G
Lesca
Anne-Marie
AM
Ouvrard-Hernandez
Valérie
V
Fraix
Stephane
S
Palfi
Marie-Odile
MO
Habert
Bertrand
B
Gaymard
Jean-Claude
JC
Dussaule
Pierre
P
Pollak
Marie
M
Vidailhet
Alexandra
A
Durr
Jean-Claude
JC
Barbot
Véronique
V
Gourlet
Alexis
A
Brice
Mathieu
M
Anheim
D000328:Adult; D000368:Aged; D001259:Ataxia / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009462:Neurology / Q000592:standards; D020734:Parkinsonian Disorders / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D017410:Practice Guidelines as Topic / Q000592:standards; D014202:Tremor / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology