Klinefelter’s syndrome (KS) is a condition that results in boys who have an extra X chromosome in most of their cells. The first documented case was in 1942 and it is the second most common extra chromosome condition, occurring in about 1 out of every 500-1,000 newborn males. Women who have pregnancies after age 35 are slightly more likely to have baby boys with this syndrome. Affected males are often referred to as XXYs or 47s as the average human has 46 chromosomes while those with Klinefelter’s have 47.
The extra X chromosome is retained because of nondisjunction or abnormal chromatid separation in meiosis. In all mammals with more than one X chromosome, including normal XX females, the genes on all but one X are not expressed in what is known as X inactivation. A few genes however, have corresponding genes on the Y and are capable of being expressed anyway which may be responsible for the symptoms that are associated with Klinefelter’s.
Boys with KS are phenotypically male. They may experience learning difficulties especially where language is involved, and may require speech therapy at an early age. They may also have difficulty in concentrating and socializing. At puberty, blood testosterone levels are generally normal initially, but may fail to rise into the normal adult range. A boy may assume a more female “pear” shape and muscle development, facial hair growth, and sexual interested may be reduced because of low testosterone. The seminiferous tubules of the testes can become filled with hyaline which hardens and blocks the tubules, and the tissue or cells surrounding them can shrink and become permanently scarred or damaged.
The most common symptom of KS men is sterility. Other possible characteristics vary largely and include no signs of affectedness at all. Gynecomastia or increased breast tissue is present in about a third of all affected individuals, but only about 10% require surgery. Hypogonadism or decreased testicular hormone function often occurs, with affected individuals having a low serum testosterone level and microorchidism or small testicles. The more severe end of the symptom spectrum is associated with an increased risk of osteoporosis, breast cancer, and germ cell tumors which are risks common to women.
Some KS males have what is known as mosaicism. In mosaicisim, some of the cells in the body are ordinary 46 chromosomal XY while others are not. Some of these individuals, because of the location of the 46 XYs, are able to produce sperm regularly and father children.
Generally adult men are diagnosed after they discover their infertility while children are often brought to the doctor because of learning problems. In either case, testosterone therapy may be prescribed to increase strength, improve appearance of muscles, grow body hair, increase sex drive, and improve concentration. Some men on testosterone therapy have even been able to father children.
To some, Klinefelter’s is a disease, but to me, it is simply a human variation. While symptoms can be severe and life altering for many of the affected, there are men that live entirely normal lives without ever being diagnosed, as well as men that are diagnosed and treated for all of their symptoms, including infertility. Additionally, scientists have noted that X-linked recessive conditions, such as hemophilia, occur even less frequently in KS males than in normal XY males because of X inactivation (typically normal XX females are only carriers). If males can lead normal lives with KS, then there is a possibility that this connection between KS and X-linked recessive conditions is an evolutionary development that will prevent some of these X-linked conditions from being expressed phenotypically. If a normal XX female is a carrier, but she has an XXY KS son, then the condition would never be expressed.
Generally speaking, the existence of humans with more than 46 chromosomes is becoming more common and in such a technological age, the possibilities are endless. As more and more KS boys are being diagnosed before birth, treated, and living lives of complete normalcy, I have to wonder whether scientists will ever be able to control the condition entirely. If so, what might this mean for cloning? Sex selection before (and maybe even during) pregnancy? Continuation of the human race? Without much evidence from the past to go on, our only choice is to wait and see what the future will bring.