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.

Background/Aims: Klinefelter syndrome (KS) is characterized by the karyotype 47,XXY. In this study, we evaluated the physical and testicular failure phenotypes of infants and young boys with KS. Methods: The evaluation included auxologic measurements, biologic indices of testicular function, and clinical assessment of muscle tone in 22 infants and young boys with KS, ages 1–23 months. Results: Mean length, weight, and head circumference in SDS were generally within the normal range at –0.3 ± 1.0, –0.1 ± 1.4, and 0.0 ± 1.5, respectively. Mean penile length and testicular volume SDS were –0.9 ± 0.8 and –1.1 ± 0.8, indicating significantly reduced penile and testicular size. Mean testosterone levels for the boys ≤6 and >6–23 months were 128 ± 131 (4.4 ± 4.5 nmol/l) and 9.5 ± 7.2 ng/dl (0.3 ± 0.2 nmol/l), respectively. High-arched palate was observed in 6/17 boys and clinodactyly (5th finger) was observed in 15/16 boys. Hypotonia was evaluated clinically and was noted to be present in 12/17 boys. Conclusion: The physical phenotype in infants and young boys with KS (1–23 months old) includes normal auxologic measurements and early evidence of testicular failure. Muscle tone was decreased in most of the boys. Testicular volume and penile length were diminished, indicating early androgen deficiency. The neonatal surge in testosterone was attenuated in our KS population. Thus, infants and young boys with KS have evidence of early testicular failure. The etiology of this failure and the clinical role of early androgen replacement require further study.

BACKGROUND Short stature and ovarian failure are characteristic features of Turner’s syndrome. Although recombinant human growth hormone is commonly used to treat the short stature associated with this syndrome, a randomized, placebo-controlled trial is needed to document whether such treatment increases adult height. Furthermore, it is not known whether childhood estrogen replacement combined with growth hormone therapy provides additional benefit. We examined the independent and combined effects of growth hormone and early, ultra-low-dose estrogen on adult height in girls with Turner’s syndrome. METHODS In this double-blind, placebo-controlled trial, we randomly assigned 149 girls, 5.0 to 12.5 years of age, to four groups: double placebo (placebo injection plus childhood oral placebo, 39 patients), estrogen alone (placebo injection plus childhood oral low-dose estrogen, 40), growth hormone alone (growth hormone injection plus childhood oral placebo, 35), and growth hormone–estrogen (growth hormone injection plus childhood oral low-dose estrogen, 35). The dose of growth hormone was 0.1 mg per kilogram of body weight three times per week. The doses of ethinyl estradiol (or placebo) were adjusted for chronologic age and pubertal status. At the first visit after the age of 12.0 years, patients in all treatment groups received escalating doses of ethinyl estradiol. Growth hormone injections were terminated when adult height was reached. RESULTS The mean standard-deviation scores for adult height, attained at an average age of 17.0±1.0 years, after an average study period of 7.2±2.5 years were −2.81±0.85, −3.39±0.74, −2.29±1.10, and −2.10±1.02 for the double-placebo, estrogen-alone, growth hormone–alone, and growth hormone–estrogen groups, respectively (P<0.001). The overall effect of growth hormone treatment (vs. placebo) on adult height was a 0.78±0.13 increase in the height standard-deviation score (5.0 cm) (P<0.001); adult height was greater in the growth hormone–estrogen group than in the growth hormone–alone group, by 0.32±0.17 standard-deviation score (2.1 cm) (P = 0.059), suggesting a modest synergy between childhood low-dose ethinyl estradiol and growth hormone. CONCLUSIONS Our study shows that growth hormone treatment increases adult height in patients with Turner’s syndrome. In addition, the data suggest that combining childhood ultra-low-dose estrogen with growth hormone may improve growth and provide other potential benefits associated with early initiation of estrogen replacement. (Funded by the National Institute of Child Health and Human Development and Eli Lilly; ClinicalTrials.gov number, NCT00001221.)