Fragile X premutation carriers: characteristic MR imaging findings of adult male patients with progressive cerebellar and cognitive dysfunction.
OBJECTIVE
Our purpose was to characterize the findings of MR imaging of the brain of adult male fragile X premutation carriers with a recently identified disorder characterized by ataxia, tremor, rigidity, and cognitive dysfunction.


METHODS
MR imaging studies of the brain of 17 male patients were characterized for signal intensity and for size of ventricles, cerebral and cerebellar sulci, and brain stem. Comparison was made with age- and sex-matched control participants. Southern blot and/or polymerase chain reaction methods were used to analyze CGG trinucleotide repeats in the fragile X mental retardation 1 gene.


RESULTS
Fifteen of 17 patients showed symmetrically decreased T1 and increased T2 signal intensity in cerebellar white matter lateral, superior, and inferior to the dentate nuclei. Fourteen of 17 had similar signal intensity alterations in the middle cerebellar peduncles. Cerebellar cortical atrophy was present in 16 of 17 and cerebral atrophy in 17 of 17. Evan's Index as a measure of ventricular size averaged 0.35 (range, 0.25-0.46), with that for age-matched control participants averaging 0.28 (range, 0.24-0.31) (P <.005). The mean third ventricle width was 11 mm (for control participants, 6 mm; P <.01). Corpus callosum was thinned in 14 of 16 participants. Middle cerebellar peduncles were atrophic when compared with those of control participants (P <.005). Pontine transverse dimension was 25 mm (for control participants, 31 mm; P <.005), and rostral-caudal length averaged 26 mm (for control participants, 29 mm; P <.005). CGG repeats clustered in the low to mid premutation range (86 +/- 10 CGG repeats) in the 17 patients.


CONCLUSIONS
MR imaging findings in symptomatic male fragile X premutation carriers are characteristic of this disorder. Recognition of these alterations may support a specific diagnosis and may have implications for the potential occurrence of fragile X syndrome in the children of reproductive age female relatives.
Brunberg
James A
JA
Department of Radiology, University of California, Davis, School of Medicine, Sacramento, CA 95817, USA.
Jacquemont
Sebastien
S
Hagerman
Randi J
RJ
Berry-Kravis
Elizabeth M
EM
Grigsby
Jim
J
Leehey
Maureen A
MA
Tassone
Flora
F
Brown
W Ted
WT
Greco
Claudia M
CM
Hagerman
Paul J
PJ
D000368:Aged; D002525:Cerebellar Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002526:Cerebellar Diseases / Q000175:diagnosis / Q000503:physiopathology; D002552:Cerebral Ventricles / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000175:diagnosis / Q000503:physiopathology; D018450:Disease Progression; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000503:physiopathology; D005819:Genetic Markers / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007360:Intelligence / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D011859:Radiography; D012720:Severity of Illness Index; D014202:Tremor / Q000209:etiology / Q000503:physiopathology; D018911:Trinucleotide Repeats / Q000502:physiology
D051860:Fragile X Messenger Ribonucleoprotein 1; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human