Klinefelter Syndrome

Excerpt

Klinefelter syndrome is a genetic condition that affects males and is characterized by the presence of 2 or more X chromosomes. The clinical phenotype was first described in 1942 by American physician Dr. Harry Klinefelter. Affected individuals often present with tall stature, small testes, gynecomastia, and azoospermia. The genetic etiology—supernumerary X chromosomes, typically 47,XXY—was identified in 1959. Additional X chromosomes contribute to testicular hyalinization, fibrosis, and hypofunction, leading to genital abnormalities, most commonly hypogonadism and infertility.

Neurocognitive differences began to gain broader recognition during the mid-to-late 20th century. Androgen replacement, along with neuropsychological and adaptive therapies, often supports effective clinical management. However, clinical care remains inconsistent due to delayed diagnosis, lack of standardized treatment protocols, and limited access to affordable therapies.

A similar but less common condition, Jacobs syndrome, is characterized by the 47,XYY genotype. Affected individuals are phenotypically male and may present with antisocial tendencies, asthma, autism, seizures, infertility, tall stature, macrocephaly, and hypertelorism. Please see StatPearls' companion resource, "Jacobs Syndrome," for further information.