[Endocrine and psychological changes in polysomy 48,XXXY].

14 year-old male patient was referred to the endocrinology utpatient clinic for hypogonadism. He had an unremarkble family and personal history. He was born in China, and ad lived in Spain with his biological family since the age of hree. This boy was referred by the urology outpatient clinic ue to delayed genital development possibly due to hypergnadotropic hypogonadism with a total testosterone level of .7 nmol/L (reference range: 9.9--27.8), FSH 18.3 IU/L, and H 13.3 IU/L (1--25). His family reported poor academic performance, diffiulties in relations with other students, and progressive ehavioral changes (attention deficit, irritability, impulse ontrol problems) in the previous two years. Physical examination found a weight of 50.5 kg, a height f 169 cm (97th percentile of height and 50th percentile f weight for Chinese adolescents of similar chronological ge),1 and an arm span of 173 cm. He had a longilinear ody habitus, pectus excavatum, kyphoscoliotic pattern, rominent elbows, and increased abdominal fat. Low hair mplantation, abnormal ears, hypertelorism, and epicanthus ere also found. As regards secondary sexual characterisics, he had no pubic and axillary hair and showed infantile enitalia (2-mL testes, 3-cm penis). The rest of the examiation was unremarkable (Fig. 1). Based on these findings, laboratory tests were requested, ncluding a hormone profile, X-rays of the left hand, and aryotype. The patient was also referred to the infanile mental health unit (USMI). Results of supplemental ests were as follows: total testosterone, 5.5 nmol/L; sex ormone-binding globulin (SHBG), 29.9 nmol/L (NV 10--80); H, 29.6 IU/L; FSH, 37.3 IU/L; 17-beta-estradiol, 24 pmol/L 20--1800); TSH, 3.93 U/mL (0.4--4); total cholesterol, 06 mg/dL (150--200); and triglycerides, 58 mg/dL (70--170). due to Klinefelter-like syndrome secondary to aneuploidy 48,XXXY was therefore made. Treatment was started with testosterone cypionate 50 mg every 4 weeks by the intramuscular route, with three-monthly dose titration based on total testosterone and gonadotropin (FSH and LH) levels. Drug treatment was well tolerated and had no influence on behavior. Based on recommendations by the USMI, the patient entered a specific support and follow-up program at school. Klinefelter syndrome encompasses a group of disorders characterized by the presence of at least one X chromosome additional to the normal male karyotype, 46,XY. The classical form is a karyotype 47,XXY, but there are other much more uncommon variants, such as those caused by aneuploidies 48,XXYY, 49,XXXXY, and 48,XXXY.2 The 47,XXY is the most common chromosome abnormality in humans, with an incidence of one case per 650 males born. The incidence of the 48,XXXY variant is very low and is estimated at approximately 1:50,000 males born.3 While patients with these polysomies share common clinical characteristics, there are differential traits between the different forms reported. This syndrome is traditionally characterized by tall height, narrow shoulders, gynecomastia, decreased testicular size and penis length, facial dysmorphism, hypergonadotropic hypogonadism, and mental retardation, among other changes. These traits vary depending on the underlying chromosome abnormality and specifically on the number of surplus X chromosomes. Thus, patients with polysomy 48,XXXY have higher mean heights as compared to those with polysomy 47,XXY (190 cm versus 179--188 cm) and are more likely to have congenital malformations such as radioulnar synostoses or clinodactyly.3,4 Facial and body dysmorphism (hypertelorism, epicanthus, narrow lid opening, low hairline implantation, flat feet, joint hyperextensibility and hyperlaxity) are also more common in polysomy 48,XXXY. Decreased testicular volume (less than 3 mL and usually lower than 1.5 mL) is a constant trait, and is also more likely in patients with polysomy 48,XXXY.3