Androgen Treatment Effects on Motor Function, Cognition, and Behavior in Boys with Klinefelter Syndrome.

OBJECTIVES: To examine the effects of early low-dose androgen on motor, cognitive, and behavioral function in prepubertal boys with Klinefelter syndrome (47,XXY). STUDY DESIGN: Double-blind trial of 84 boys, ages 4-12 years, randomized to oxandrolone (Ox; 0.06?mg/kg daily; n?=?43) or placebo (Pl; n?=?41) for 24 months. Standardized assessments were performed at baseline and every 12 months for 24 months evaluating motor, cognitive, and behavioral function. RESULTS: The 24-month outcomes were better in the Ox vs. Pl group on 1 of 5 primary endpoints (motor function/strength): Bruininks Visual-Motor scale (P?=?.005), without significant differences between the 2 groups for the other 4 components. Secondary analyses suggested improvement in the Ox vs. Pl group in the anxiety/depression (P?=?.03) and social problems (P?=?.01) scales on the Child Behavior Checklist, anxiety (P?=?.04) on the Piers Harris Self Concept Scale, and interpersonal problems (P?=?.02) on the Children's Depression Inventory, without significant differences in hyperactive or aggressive behaviors. CONCLUSIONS: This double-blind, randomized trial demonstrates that 24 months of childhood low-dose androgen treatment in boys with Klinefelter syndrome benefited 1 of 5 primary endpoints (visual-motor function). Secondary analyses demonstrated positive effects of androgen on aspects of psychosocial function (anxiety, depression, social problems), without significant effects on cognitive function, or hyperactive or aggressive behaviors. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00348946.

47,XYY syndrome: clinical phenotype and timing of ascertainment.

OBJECTIVE: To describe auxologic, physical, and behavioral features in a large cohort of males with 47,XYY (XYY), ages newborn to young adult. STUDY DESIGN: This is a cross-sectional descriptive study of male subjects with XYY who were evaluated at 1 of 2 specialized academic sites. Subjects underwent a history, physical examination, laboratory testing, and cognitive/behavioral evaluation. RESULTS: In 90 males with XYY (mean age 9.6 ± 5.3 years [range 0.5-36.5]), mean height SD was above average (1.0 ± 1.2 SD). Macrocephaly (head circumference >2 SD) was noted in 28/84 (33%), hypotonia in 57/90 (63%), clinodactyly in 47/90 (52%), and hypertelorism in 53/90 (59%). There was testicular enlargement for age (>2 SD) in 41/82 (50%), but no increase in genital anomalies. No physical phenotypic differences were seen in boys diagnosed prenatally vs postnatally. Testosterone, luteinizing hormone, and follicle stimulating hormone levels were in the normal range in most boys. There was an increased incidence of asthma, seizures, tremor, and autistic spectrum disorder (ASD) compared with the general population rates. Prenatally diagnosed boys scored significantly better on cognitive testing and were less likely to be diagnosed with ASD (P < .01). CONCLUSIONS: The XYY phenotype commonly includes tall stature, macrocephaly, macroorchidism, hypotonia, hypertelorism, and tremor. Physical phenotypic features were similar in boys diagnosed prenatally vs postnatally. Prenatal diagnosis was associated with higher cognitive function and less likelihood of an ASD diagnosis.

Effects of treatment with oxandrolone for 4 years on the frequency of severe arithmetic learning disability in girls with Turner syndrome.

OBJECTIVES: To study androgen treatment effects on arithmetic performance in girls with Turner syndrome. STUDY DESIGN: Forty-four girls, ages 10 to 14 years at baseline, completed 4 years of treatment with oxandrolone (Ox) or placebo (Pl). All received growth hormone and estrogen replacement therapy. We assessed the number of girls with severe learning disability (LD, standard score

Effect of ascertainment and genetic features on the phenotype of Klinefelter syndrome.

OBJECTIVE: To describe the Klinefelter Syndrome (KS) phenotype during childhood in a large cohort. STUDY DESIGN: Clinical assessment, measurement of hormonal indices of testicular function, and parent of origin of extra X chromosome were assessed in a cross-sectional study of 55 boys with KS, aged 2.0 to 14.6 years, at an outpatient center. RESULTS: Mean height and body mass index SD scores (SDS +/- SD) were 0.9 +/- 1.3 and 0.4 +/- 1.4, respectively. Mean penile length and testicular volume SDS were -0.5 +/- 0.9 and -0.9 +/- 1.4. Testosterone levels were in the lowest quartile of normal in 66% of the cohort. Other features included clinodactyly (74%), hypertelorism (69%), elbow dysplasia (36%), high-arched palate (37%), hypotonia (76%), and requirement for speech therapy (69%). Features were similar in boys in whom the diagnosis was made prenatally versus boys in whom the diagnosis was made postnatally. There was no evidence for a phenotypic effect of parent of origin of the extra X chromosome. CONCLUSIONS: Boys with KS commonly have reduced penile length and small testes in childhood. The phenotype in boys with KS does not differ according to ascertainment or origin of the extra X chromosome. Boys with KS may be identified before puberty by tall stature, relatively decreased penile length, clinodactyly, hypotonia, and requirement for speech therapy.

The phenotype of short stature homeobox gene (SHOX) deficiency in childhood: contrasting children with Leri-Weill dyschondrosteosis and Turner syndrome.

OBJECTIVE: To evaluate the growth disorder and phenotype in prepubertal children with Leri-Weill dyschondrosteosis (LWD), a dominantly inherited skeletal dysplasia, and to compare the findings from girls with Turner syndrome (TS). STUDY DESIGN: We studied the auxologic and phenotypic characteristics in 34 prepubertal LWD subjects (ages 1 to 10 years; 20 girls, 14 boys) with confirmed short stature homeobox-containing gene (SHOX) abnormalities. For comparative purposes, we evaluated similar physical and growth parameters in 76 girls with TS (ages 1 to 19 years) and 24 girls with LWD (ages 1 to 15 years) by using data collected from the postmarketing observational study, GeNeSIS. RESULTS: In the clinic sample LWD subjects, height standard deviation score ranged from -5.5 to +0.1 (-2.3 +/- 1.3, girls and -1.8 +/- 0.6, boys). Wrist changes related to Madelung deformity were present in 18 of 34 (53%) LWD subjects. In comparing the LWD and TS populations in the GeNeSIS sample, Madelung deformity, increased carrying angle, and scoliosis were more prevalent in the LWD population, whereas high arched palate was similarly prevalent in the two populations. CONCLUSIONS: Short stature is common in both LWD (girls and boys) and TS (girls). Clinical clues to the diagnosis of SHOX haploinsufficiency in childhood include short stature, short limbs, wrist changes, and tibial bowing.