Klinefelter Syndrome (47,XXY)
Klinefelter syndrome is ≥ two X chromosomes plus one Y, resulting in a phenotypic male.
Klinefelter syndrome is the most common sex chromosome disorder, occurring in about 1/500 live male births. The extra X chromosome is maternally derived in 60% of cases. Germ cells do not survive in the testes, leading to decreased sperm and androgens.
Affected boys tend to be tall with disproportionately long arms and legs. They often have small, firm testes, and about 30% develop gynecomastia.
Puberty usually occurs at the normal age, but often facial hair growth is light. There is a predisposition for verbal learning disorders. Clinical variation is great, and many 47,XXY males have normal appearance and intellect. Testicular development varies from hyalinized nonfunctional tubules to some production of spermatozoa; urinary excretion of follicle-stimulating hormone is frequently increased.
Mosaicism occurs in about 15% of cases. These men may be fertile. Some affected men have 3, 4, and even 5 X chromosomes along with the Y. As the number of X chromosomes increases, the severity of intellectual disability and of malformations also increases. Each extra X is associated with a 15- to 16-point reduction in IQ, with language most affected, particularly expressive language skills.
The diagnosis of Klinefelter syndrome is suspected on physical examination of an adolescent with small testes and gynecomastia. Many men are diagnosed during an infertility evaluation (probably all nonmosaic 47,XXY males are infertile).
Diagnosis is confirmed by cytogenetic analysis (karyotyping, fluorescent in situ hybridization [FISH] analysis, and/or chromosomal microarray analysis [CMA]).
Males with Klinefelter syndrome should have lifelong testosterone supplementation beginning at puberty to ensure the development of male sexual characteristics, muscle bulk, bone structure, and better psychosocial functioning.
Boys with Klinefelter syndrome usually benefit from speech and language therapy and neuropsychologic testing for language comprehension, reading, and cognitive deficits.
After the onset of puberty, boys should receive counseling regarding fertility preservation.