Neuropsychological profiles of adults with Klinefelter syndrome KYLE BRAUER BOONE, 1 RONALD S. SWERDLOFF, 2 BRUCE L. MILLER, 3 DANIEL H. GESCHWIND, 4 JILL RAZANI, 1 ALISON LEE, 1 IRENE GAW GONZALO, 2 ANNA HADDAL, 2 KATHERINE RANKIN, 1 PO LU, 1 and LYNN PAUL 1 1 Department of Psychiatry, Harbor–UCLA Medical Center 2 Department of Medicine (Endocrinology), Harbor–UCLA Medical Center 3 Department of Neurology, UCSF 4 Department of Neurology, UCLA (Received September 27, 1999; Revised May 3, 2000; Accepted May 4, 2000) Abstract Children and adolescents with Klinefelter syndrome (XXY) have been reported to show deficits in language processing including VIQ , PIQ and a learning disability in reading and spelling. However, whether this is characteristic of adults with Klinefelter syndrome has not been established. Thirty-five men with Klinefelter syndrome, aged 16 to 61, and 22 controls were evaluated with a comprehensive neuropsychological battery. The Klinefelter patients scored significantly below controls in language skills, verbal processing speed, verbal and nonverbal executive abilities, and motor dexterity. Within the Klinefelter sample, three cognitive subgroups were identified: VIQ 7 or more points below PIQ ( n 5 10), VIQ within 6 points of PIQ ( n 5 12), and PIQ 7 or more points below VIQ ( n 5 12). The deficits detected in language, verbal processing speed, and verbal executive skills were found to be isolated to the VIQ , PIQ subgroup, while the abnormalities in motor dexterity and nonverbal executive skills were confined to the PIQ , VIQ subgroup. Older age was significantly correlated with increases in VIQ relative to PIQ in the patient group, which suggests the intriguing possibility that the PIQ , VIQ subgroup primarily emerges in young adulthood, perhaps in response to the reported hormonal abnormalities detected in Klinefelter syndrome patients during puberty. ( JINS, 2001, 7, 446– 456) Keywords: Klinefelter syndrome; 47,XXY; Sex chromosome abnormalities; Neuropsychological scores INTRODUCTION Klinefelter syndrome is a condition in which males are born with one or more extra X chromosomes. It is the most com- mon sex chromosome disorder (Wesner et al., 1973) with a prevalence of approximately 1 in 500 to 800 phenotypic males (Jacobs, 1979; Maclean et al., 1961). The Klinefelter syndrome phenotype, as originally described, consists of a number of characteristics including small firm testes, infer- tility (azoospermia), varying degrees of impaired sexual maturation, gynecomastia and elevated gonadotropin levels (Klinefelter et al., 1942). Subsequent reports expanded the clinical manifestations of the disorder including recogni- tion of cognitive and behavioral abnormalities (Hseah et al., 1978; Leonard et al., 1978; Paulsen et al., 1968; Robinson et al., 1979). Unfortunately, most of the empirical research on the cognitive and behavioral disturbances are based on individual case reports or relatively small samples. In ad- dition, the data that are available have generally been con- fined to children and adolescents, and have primarily focused on assessment of academic achievement and intellectual levels rather than a comprehensive investigation of multi- ple cognitive domains. The presence of learning disabilities in reading and spell- ing in children and adolescents with Klinefelter syndrome have been widely reported (Annell et al., 1970; Bender et al., 1986, 1987, 1993; Funderburk & Ferjo, 1978; Graham et al., 1988; Leonard, 1991; Mandoki et al., 1991; Nielsen, 1991; Nielsen et al., 1970; Pennington et al., 1982; Ratcliffe et al., 1991; Robinson et al., 1991a, 1991b; Rovet et al., 1995, 1996; Stewart et al., 1986, 1991; Walzer et al., 1986, 1991; Wesner et al., 1973) as well as collateral language distur- bances in comprehension, expression, and verbal process- ing speed (Bender et al., 1983, 1987, 1989, 1993; Funderburk & Ferjo, 1978; Graham et al., 1988; Haka-Ikse et al., 1978; Mandoki et al., 1991; Netley & Rovet, 1982; Robinson et al., Reprint requests to: Kyle Brauer Boone, Ph.D., ABPP-ABCN, Box 495, Harbor-UCLA Medical Center, Department of Psychiatry, 1000 W. Carson Street, F-9, Torrance, CA 90509-2910. E-mail: kboone@rei.edu Journal of the International Neuropsychological Society (2001), 7, 446–456. Copyright © 2001 INS. Published by Cambridge University Press. Printed in the USA. 446