Central Precocious Puberty in a Boy with Klinefelter Syndrome and Congenital Adrenal Hyperplasia

Central precocious puberty in a boy with Klinefelter syndrome and congenital adrenal hyperplasiaKlinefelter syndrome (KS) is the most common sex chromosome abnormality in males and is characterized by small testes, hypergonadotropic hypogonadism, gynecomastia, and impaired spermatogenesis.Approximately 80% of affected individuals have a 47,XXY karyotype, while the remainder show mosaicism or other structural X chromosome abnormalities.[1] Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder of adrenal steroidogenesis, most commonly caused by 21-hydroxylase deficiency (21-OHD) due to mutations in the CYP21A2 gene.Classic CAH is divided into salt-wasting and simple virilizing forms, the latter accounting for approximately 25% of cases.[2]CAH typically presents with androgen excess and gonadotropin-independent precocious puberty in boys, characterized by suppressed luteinizing hormone (LH), elevated adrenal androgens, and prepubertal testicular volume.However, prolonged androgen exposure may rarely lead to secondary activation of the hypothalamic-pituitary-gonadal (HPG) axis, resulting in central precocious puberty (CPP).[3] The coexistence of CAH and KS is extremely rare, with only seven cases reported to date, and CPP in this context has not been well described [4-10] (Table 1).We report a rare case of a young boy with KS and CAH due to 21-OHD complicated by central precocious puberty, highlighting the complex interaction between adrenal and gonadal pathology.A 5-year-9-month-old boy presented with recent onset of pubic hair development.He was born at 39 weeks' gestation via planned cesarean section (birth weight 3,390 g) following a natural conception without assisted reproductive technology, and the pregnancy was not of advanced maternal age.KS (47,XXY) was suspected via neonatal genetic screening (G-scan) and confirmed by chromosomal analysis at birth.There were no prenatal or neonatal clinical features suggestive of KS.The neonatal screening test for CAH including 17-hydroxyprogesterone, was reported to be within the normal range.He had no history of neonatal salt-wasting, dehydration, or vomiting.No facial dysmorphism