Sex chromosome abnormalities are a group of disorders that involve deranged number or structure of the X and Y chromosomes. Klinefelter syndrome is the most common sex chromosome abnormality causing hypergonadotropic hypogonadism and neurodevelopmental deficits.1Swerdlow A.J. Higgins C.D. Schoemaker M.J. Wright A.F. Jacobs P.A. Mortality in patients with Klinefelter syndrome in Britain: a cohort study.J Clin Endocrinol Metab. 2005; 90: 6516-6522Crossref PubMed Scopus (191) Google Scholar This disorder presents with a 47, XXY karyotype in 1 per 450 male births. On the other hand, 48, XXYY is one of the rarer variants which presents in 1 per 18,000 to 1 per 40,000 of all male births.2Blumling A.A. Martyn K. Talboy A. Close S. Rare sex chromosome variation 48,XXYY: an integrative review.Am J Med Genet C Semin Med Genet. 2020; 184: 386-403Crossref PubMed Scopus (5) Google Scholar 48, XXYY syndrome results from the presence of an extra copy of both sex chromosomes. It is not inherited but occurs sporadically.We present a rare, Taiwanese case of Klinefelter syndrome with 48, XXYY karyotype. A 16-year-old male adolescent was referred for clinical investigations over his tall stature. Upon physical examination, the patient weighed 89.5 kg (>97th percentile) and his height was measured at 198 cm (>97th percentile). Breasts were observed at Tanner Stage II of development. Genital examination revealed Tanner stage IV of development with bilateral, non-palpable testes; his penis had approximately 10 cm of length upon application of traction. Pubic hairs were at Tanner stage IV of development.Hemogram, liver function tests, renal function tests, electrolytes, lipids, hemoglobin A1c, thyroid function tests, calcium and total human chorionic gonadotropin (HCG) were within normal reference ranges. Endocrine function tests showed follicle-stimulating hormone (FSH) 46.59 mIU/ml (1.50–12.40), Luteining hormone (LH) 32.78 mIU/ml (1.70–8.60), estradiol (E2) 25.05 mIU/ml (11.30–43.20), Dehydroepiandrosterone Sulfate (DHEA-SO4) 177.9 ug/dl (145–395), testosterone 151 ng/dl (100–1200), prolactin 14.6 ng/ml (4.04–15.2), insulin-like growth factor-1311 ng/ml (119–511), and growth hormone 0.194 ng/ml (0.003–3.607).Scrotal ultrasound showed bilaterally small testes (right testicle: 1.1 × 0.8 × 1.6 cm; left testicle 1.2 × 0.8 × 1.6 cm). Bone age was 16–17 years. Brain magnetic resonance imaging with contrast showed no abnormality in the hypothalamopituitary axis. Chromosomal analysis showed a 48, XXYY karyotype (Fig. 1). Since there is an increased risk of neuropsychiatric problem in 48, XXYY. The patient has not developed any mental or behavior disorders. We will keep follow up and if there are any cognitive, emotional, or social function problem developed, early transferring to psychiatric specialist is necessary.48, XXYY karyotype presentations may present similarly to Klinefelter syndrome with noticeable phenotypic differences including tall eunuchoid body habitus, small testicles, and gynecomastia. They may have infertility, mild craniofacial dysmorphism, poor dentition, radioulnar synostosis, intention tremor, peripheral vascular disease, and shy behavior.2Blumling A.A. Martyn K. Talboy A. Close S. Rare sex chromosome variation 48,XXYY: an integrative review.Am J Med Genet C Semin Med Genet. 2020; 184: 386-403Crossref PubMed Scopus (5) Google Scholar 48, XXYY syndrome is associated with greater risk for attention deficit hyperactivity disorder and neurocognitive disorders than Klinefelter syndrome.3Tartaglia N.R. Ayari N. Hutaff-Lee C. Boada R. Attention-deficit hyperactivity disorder symptoms in children and adolescents with sex chromosome aneuploidy: XXY, XXX, XYY, and XXYY.J Dev Behav Pediatr. 2012; 33: 309-318Crossref PubMed Scopus (81) Google Scholar Primary hypogonadism with serum testosterone concentrations within low-normal ranges and markedly elevated gonadotropin values support the diagnosis. Furthermore, genetic testing through peripheral blood chromosome studies yield definitive diagnosis. Patients with 48, XXYY syndrome and hypogonadism may benefit from testosterone replacement.FundingThis study was supported by the Tri-Service General Hospital Research Foundation (TSGH-E−110186, TSGH-E−111195), and the sponsor had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Declaration of competing interestThere is no conflict of interest. Sex chromosome abnormalities are a group of disorders that involve deranged number or structure of the X and Y chromosomes. Klinefelter syndrome is the most common sex chromosome abnormality causing hypergonadotropic hypogonadism and neurodevelopmental deficits.1Swerdlow A.J. Higgins C.D. Schoemaker M.J. Wright A.F. Jacobs P.A. Mortality in patients with Klinefelter syndrome in Britain: a cohort study.J Clin Endocrinol Metab. 2005; 90: 6516-6522Crossref PubMed Scopus (191) Google Scholar This disorder presents with a 47, XXY karyotype in 1 per 450 male births. On the other hand, 48, XXYY is one of the rarer variants which presents in 1 per 18,000 to 1 per 40,000 of all male births.2Blumling A.A. Martyn K. Talboy A. Close S. Rare sex chromosome variation 48,XXYY: an integrative review.Am J Med Genet C Semin Med Genet. 2020; 184: 386-403Crossref PubMed Scopus (5) Google Scholar 48, XXYY syndrome results from the presence of an extra copy of both sex chromosomes. It is not inherited but occurs sporadically. We present a rare, Taiwanese case of Klinefelter syndrome with 48, XXYY karyotype. A 16-year-old male adolescent was referred for clinical investigations over his tall stature. Upon physical examination, the patient weighed 89.5 kg (>97th percentile) and his height was measured at 198 cm (>97th percentile). Breasts were observed at Tanner Stage II of development. Genital examination revealed Tanner stage IV of development with bilateral, non-palpable testes; his penis had approximately 10 cm of length upon application of traction. Pubic hairs were at Tanner stage IV of development. Hemogram, liver function tests, renal function tests, electrolytes, lipids, hemoglobin A1c, thyroid function tests, calcium and total human chorionic gonadotropin (HCG) were within normal reference ranges. Endocrine function tests showed follicle-stimulating hormone (FSH) 46.59 mIU/ml (1.50–12.40), Luteining hormone (LH) 32.78 mIU/ml (1.70–8.60), estradiol (E2) 25.05 mIU/ml (11.30–43.20), Dehydroepiandrosterone Sulfate (DHEA-SO4) 177.9 ug/dl (145–395), testosterone 151 ng/dl (100–1200), prolactin 14.6 ng/ml (4.04–15.2), insulin-like growth factor-1311 ng/ml (119–511), and growth hormone 0.194 ng/ml (0.003–3.607). Scrotal ultrasound showed bilaterally small testes (right testicle: 1.1 × 0.8 × 1.6 cm; left testicle 1.2 × 0.8 × 1.6 cm). Bone age was 16–17 years. Brain magnetic resonance imaging with contrast showed no abnormality in the hypothalamopituitary axis. Chromosomal analysis showed a 48, XXYY karyotype (Fig. 1). Since there is an increased risk of neuropsychiatric problem in 48, XXYY. The patient has not developed any mental or behavior disorders. We will keep follow up and if there are any cognitive, emotional, or social function problem developed, early transferring to psychiatric specialist is necessary. 48, XXYY karyotype presentations may present similarly to Klinefelter syndrome with noticeable phenotypic differences including tall eunuchoid body habitus, small testicles, and gynecomastia. They may have infertility, mild craniofacial dysmorphism, poor dentition, radioulnar synostosis, intention tremor, peripheral vascular disease, and shy behavior.2Blumling A.A. Martyn K. Talboy A. Close S. Rare sex chromosome variation 48,XXYY: an integrative review.Am J Med Genet C Semin Med Genet. 2020; 184: 386-403Crossref PubMed Scopus (5) Google Scholar 48, XXYY syndrome is associated with greater risk for attention deficit hyperactivity disorder and neurocognitive disorders than Klinefelter syndrome.3Tartaglia N.R. Ayari N. Hutaff-Lee C. Boada R. Attention-deficit hyperactivity disorder symptoms in children and adolescents with sex chromosome aneuploidy: XXY, XXX, XYY, and XXYY.J Dev Behav Pediatr. 2012; 33: 309-318Crossref PubMed Scopus (81) Google Scholar Primary hypogonadism with serum testosterone concentrations within low-normal ranges and markedly elevated gonadotropin values support the diagnosis. Furthermore, genetic testing through peripheral blood chromosome studies yield definitive diagnosis. Patients with 48, XXYY syndrome and hypogonadism may benefit from testosterone replacement. FundingThis study was supported by the Tri-Service General Hospital Research Foundation (TSGH-E−110186, TSGH-E−111195), and the sponsor had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.