Klinefelter syndrome is a sex chromosome disorder that is characterized by genotype.
USMLE® Step 1 style questions USMLE
An 18-year-old man comes to his primary care physician for an annual check-up. He is in his first year of college and says he is overall in good health. He admits that he has been having difficulty paying attention in class and has had difficulties talking to and getting to know girls. He believes that this is because of his prominent breasts, which he has had most of his life. He is a well-developed male with tall stature, mild gynecomastia, and hypogonadism (as shown in the image below). Which of the following is the most likely cause of these characteristic findings in the patient?
Content Reviewers:Rishi Desai, MD, MPH
Klinefelter syndrome, named after Dr. Harry Klinefelter who first identified it, is a chromosomal problem where a person with an XY genotype - biologically a male - inherits at least one extra X-chromosome, and sometimes a few extra ones.
Having an extra X chromosome makes the testicular cells generate less testosterone, which is the hormone responsible for primary sex characteristics like development of the sex organs as well as secondary sex characteristics like height and body shape.
It’s worth mentioning up front, that we’re using the term male here, rather than boy or man, to talk about the biological category of a person’s sex rather than a person’s gender identity.
Now, in puberty, in both males and females, the hypothalamus starts to release more gonadotropin releasing hormone, which gets the pituitary gland to release luteinizing hormone and follicle-stimulating hormone.
In males, these hormones affect the Leydig cells and the Sertoli cells.
The testosterone along with follicle-stimulating hormone, then stimulate Sertoli cells in the seminiferous tubules of the testes to make more sperm.
To main balance or homeostasis, testosterone reduces gonadotropin releasing hormone and luteinizing hormone, and Sertoli cells release the hormone inhibin which inhibits release of follicle-stimulating hormone.
In Klinefelter syndrome, this hormone balance is altered.
The extra X-chromosome interrupts the normal function of the Sertoli and Leydig cells.
This means that levels of luteinizing hormone and follicle stimulating hormone increase.
Less testosterone also suppresses testes maturation and sperm production as well as development of secondary male characteristics.
Klinefelter syndrome develops when a gamete, either a sperm or an egg, contains at least one extra X-chromosome.
Typically, a gamete with 23 chromosomes, including one sex chromosome either X or Y, develops when parent germ cells undergo the process of meiosis.
Early on in meiosis the germ cell makes a copy of all of its chromosomes, with each chromosome having sister chromatids at that point.