Klinefelter syndrome, also known as congenital testicular hypoplasia or primary small testicular evidence, was first reported and named by Klinefelter et al. in 1942. 1956 Brandbury et al. found an X chromosome in the somatic cells of such patients (normal males are X chromosome negative), and in 1959 Jacob and Strong et al. confirmed that the patient’s karyotype was 47, XXY, so the disease is also known as XXY syndrome. The karyotype is 47, XXY, so the disease is also known as XXY syndrome.1. Incidence and clinical manifestations of Klinefelter syndrome Klinefelter syndrome mainly manifests as a polysomy of the X chromosome, accounting for 0.1% to 0.2% of male newborns, 10% of azoospermic males, and 5% of severe oligospermia. The most common karyotype in Klinefelter’s syndrome is 47,XXY, which accounts for about 80% of Klinefelter’s syndrome. 15% of chimeric karyotypes, including 46,XY/47,XXY,45,X/46,XY/47,XXY,46,XX/47,,XXY, etc. Klinefelter’s syndrome is characterized by tall stature, small and hard testes, and hypoplastic secondary sex characteristics. The patient has a taller stature, thin bones, relatively long limbs, feminine physical features, sparse beard and pubic hair, small penis, low testosterone, and mild to moderate mental retardation. Usually, adult males present with infertility: azoospermia or severe oligospermia, low testosterone and resulting symptoms such as erectile dysfunction and low libido. In adolescent males, the main manifestations are genital and pubertal development disorders. In adolescent males, the testes are less than 10 ml in volume and hard in texture, and should be further evaluated for penis size, androgen, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. It has been shown that patients with Creutzfeldt-Jakob syndrome are more likely to develop tumors of extratesticular germ cell origin and are also susceptible to autoimmune diseases, and patients with Creutzfeldt-Jakob syndrome have 14 times the risk of developing systemic lupus erythematosus than normal men. 2. Clinical diagnostic karyotype analysis is the gold standard for the diagnosis of Klinefelter syndrome. For patients with high clinical suspicion of Klinefelter’s syndrome karyotype analysis is feasible to clarify the diagnosis. However, the diagnosis of Klinefelter’s syndrome can be easily missed in low percentage of chimeric Klinefelter’s syndrome.3. Prenatal diagnosis Currently, the abnormal number of fetal sex chromosomes can be suggested by non-invasive prenatal screening (NIPT). The amniotic fluid cells obtained by amniocentesis can be quickly detected by STR and FISH, but karyotype analysis is still needed to confirm the diagnosis.4. Treatment Klinefelter syndrome as a chromosomal abnormality, there is no good treatment method. Some studies have shown that patients with Klinefelter syndrome have spermatogonia at birth, but lose a large number of germ cells during puberty. Therefore, we can only recommend that patients with Klinefelter syndrome be diagnosed and treated as early as possible. After the diagnosis is confirmed by chromosomal analysis, androgen replacement therapy should be administered during puberty to maintain the male phenotype, improve the patient’s psychology, and enhance the patient’s quality of life, while reserving sperm in advance, the chances of having one’s own offspring will be greatly increased.