Fragile X premutation tremor/ataxia syndrome: molecular, clinical, and neuroimaging correlates.
We present a series of 26 patients, all >50 years of age, who are carriers of the fragile X premutation and are affected by a multisystem, progressive neurological disorder. The two main clinical features of this new syndrome are cerebellar ataxia and/or intention tremor, which were chosen as clinical inclusion criteria for this series. Other documented symptoms were short-term memory loss, executive function deficits, cognitive decline, parkinsonism, peripheral neuropathy, lower limb proximal muscle weakness, and autonomic dysfunction. Symmetrical regions of increased T2 signal intensity in the middle cerebellar peduncles and adjacent cerebellar white matter are thought to be highly sensitive for this neurologic condition, and their presence is the radiological inclusion criterion for this series. Molecular findings include elevated mRNA and low-normal or mildly decreased levels of fragile X mental retardation 1 protein. The clinical presentation of these patients, coupled with a specific lesion visible on magnetic resonance imaging and with neuropathological findings, affords a more complete delineation of this fragile X premutation-associated tremor/ataxia syndrome and distinguishes it from other movement disorders.
Jacquemont
Sébastien
S
M.I.N.D. Institute, UC Davis Medical Center, 4860 Y Street, Suite 3020, Sacramento, CA 95817, USA.
Hagerman
Randi J
RJ
Leehey
Maureen
M
Grigsby
Jim
J
Zhang
Lin
L
Brunberg
James A
JA
Greco
Claudia
C
Des Portes
Vincent
V
Jardini
Tristan
T
Levine
Richard
R
Berry-Kravis
Elizabeth
E
Brown
W Ted
WT
Schaeffer
Stephane
S
Kissel
John
J
Tassone
Flora
F
Hagerman
Paul J
PJ
D000368:Aged; D001259:Ataxia / Q000235:genetics; D001921:Brain / Q000473:pathology; D001931:Brain Mapping; D002531:Cerebellum / Q000473:pathology*; D004522:Educational Status; D005006:Ethnicity; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000473:pathology; D006580:Genetic Carrier Screening; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D018579:Patient Selection; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D014202:Tremor / Q000235:genetics
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human