Psychiatric phenotype of the fragile X-associated tremor/ataxia syndrome (FXTAS) in males: newly described fronto-subcortical dementia.
OBJECTIVE
The authors describe and quantify the neuropsychiatric symptoms present in a cohort of males with the fragile X mental retardation 1 (FMR1) premutation allele who have developed fragile X-associated tremor/ataxia syndrome (FXTAS).


METHODS
Fourteen male carriers of the FMR1 premutation who had clinical manifestations of the FXTAS syndrome and 14 age- and education-matched controls were assessed with the Neuropsychiatric Inventory (NPI), formal cognitive testing, and genetic analysis.


RESULTS
Males with FXTAS had significantly higher total NPI scores (p < .004) and significantly higher scores on the agitation/aggression (p < .004), depression (p < .004), apathy (p < .004), disinhibition (p < .004), and irritability (p < .004) scales, compared with controls. Cognitive performances on the Mini-Mental State Examination did not correlate with severity of symptoms on the NPI.


CONCLUSIONS
The neuropsychiatric manifestations of FXTAS, based on this preliminary report, appear to cluster as a fronto-subcortical dementia. Clinicians encountering patients with clinical dementia with motor symptoms suggesting FXTAS should consider genetic testing to determine whether the patient's dementia syndrome is secondary to a fragile X premutation carrier status.
Bacalman
Susan
S
M.I.N.D. Institute, and Departments of Psychiatry and Behavioral Sciences, UCDavis Medical Center, University of California-Davis, 2230 Stockton Boulevard, Sacramento, CA 95817, USA.
Farzin
Faraz
F
Bourgeois
James A
JA
Cogswell
Jennifer
J
Goodlin-Jones
Beth L
BL
Gane
Louise W
LW
Grigsby
Jim
J
Leehey
Maureen A
MA
Tassone
Flora
F
Hagerman
Randi J
RJ
D000368:Aged; D001259:Ataxia / Q000175:diagnosis / Q000235:genetics*; D003704:Dementia / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics*; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D012737:Sex Factors; D013577:Syndrome; D014202:Tremor / Q000175:diagnosis / Q000235:genetics*; D014888:Wechsler Scales
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human