NORD gratefully acknowledges Jeannie Visootsak, MD, FAAP, Associate Professor, Developmental-Behavioral Pediatrics, Department of Human Genetics & Pediatrics, Emory University School of Medicine, for assistance in the preparation of this report.
Klinefelter syndrome is a group of chromosomal disorders in males in which one or more extra X chromosomes are present. Males with the classic form of the disorder have one extra X chromosome. Males with other X and Y variations have additional X and/or Y chromosomes. The extra X and/or Y chromosome can affect physical, developmental, behavioral, and cognitive functioning. Common physical features may include tall stature, lack of secondary pubertal development, small testes (hypogonadism), delayed pubertal development, and breast development (gynecomastia) in late puberty. These features may be associated with low testosterone level and elevated gonadotropin levels.
Infants and young children with Klinefelter syndrome are sometimes initially identified because of an abnormality in the location of the urinary opening in the penis (hypospadias), small penis or testes, or developmental delay (e.g. speech delay). Older children and teenagers are sometimes diagnosed with Klinefelter syndrome if secondary sexual characteristics do not develop completely, puberty is delayed, testes are small or breast development occurs. Many males with Klinefelter syndrome are not identified until they have infertility problems as adults. Men with Klinefelter syndrome may have a relatively increased risk to develop breast cancer. Most males with Klinefelter syndrome have normal intelligence but there is a high risk of language delay and social functioning challenges. There is a correlation between the number of extra X chromosomes and the degree of physical and intellectual deficits.
Men with Klinefelter syndrome may have an increased risk for endocrine conditions such as diabetes mellitus, hypothyroidism and hypoparathyroidism and autoimmune diseases such as systemic lupus erythematosus, Sjogren syndrome and rheumatoid arthritis. For more information about these conditions, please search for them in by name in NORD’s Rare Disease Database.
Males with Klinefelter syndrome have one or more extra X chromosomes because of an error that occurs during the division of the sex chromosomes in the egg or sperm. Some males with Klinefelter syndrome are mosaic, meaning that some cells have an extra X chromosome and other cells do not. Mosaic Klinefelter syndrome occurs because of an error in the division of the sex chromosomes in the zygote after fertilization.
The extra X chromosome results in primary testicular failure leading to androgen deficiency.
The classic form of Klinefelter syndrome in which one extra X chromosome is present in all cells, occurs in approximately 1 in 500-1000 males. 80-90% of affected males have the classic type. Other X and Y variant forms of the condition occur much less frequently.
Klinefelter syndrome is diagnosed by a chromosome karyotype analysis on a blood sample. This condition can also be diagnosed prenatally on chorionic villous or amniotic fluid cells.
Klinefelter syndrome is treated with the administration of male hormones (androgens), such as testosterone enanthate or cypionate. These are given to promote the development of secondary male sexual characteristics (virilization). This hormone therapy should begin around pubertal development. Some men with Klinefelter syndrome who have gynecomastia may require surgical breast reduction for cosmetic purposes.
Speech and language therapy, physical therapy and occupational therapy may be helpful for boys with Klinefelter syndrome. A comprehensive psychoeducational evaluation is recommended to determine what resources may be helpful in the classroom. Social skills training classes can also be beneficial.
Men with Klinefelter syndrome tend to be infertile but a few men with mosaic Klinefelter syndrome have been reported to be fertile. Surgical extraction of sperm from the testes and intracytoplasmic sperm injection (ICSI) directly into an ovum is a medical technology available to assist some men with Klinefelter syndrome to father children.
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