Can Paternal Meiosis II Nondisjunction Cause an XXY Male?

A typical XXY male has an extra X chromosome in most or all of the body’s cells. This chromosome pattern is commonly called Klinefelter syndrome. The key to understanding how it can arise is to distinguish what separates in the two meiotic divisions.

In the usual case, a single nondisjunction error in paternal meiosis II does not make an XY sperm. It can make a sperm carrying two X chromosomes or two Y chromosomes, depending on which sex chromosome that cell received in meiosis I. The routes that can produce an XXY conception are different.

What separates in each meiotic division?

A typical male has one X chromosome and one Y chromosome. Before meiosis, each chromosome is copied, producing two sister chromatids joined together.

In meiosis I, the X and Y chromosomes separate into different cells. They are homologous in some regions, but they are different chromosomes. In meiosis II, the sister chromatids of each chromosome separate. A normal meiosis therefore produces sperm carrying either an X or a Y chromosome, along with one copy of each other chromosome.

Nondisjunction means that chromosomes that should separate instead go to the same cell. Which division is affected determines what ends up in the sperm.

What paternal meiosis II nondisjunction can produce

Assume meiosis I proceeds normally. One resulting cell has the X chromosome; the other has the Y. If sister chromatids fail to separate during meiosis II, the affected cell can produce one sperm with two copies of its sex chromosome and one sperm with none:

Cell entering meiosis II	Possible sperm after nondisjunction	If fertilized by a normal X egg
X-bearing cell	XX and no sex chromosome (O)	XXX or XO
Y-bearing cell	YY and O	XYY or XO

The other cell, if it divides normally, produces sperm carrying one X or one Y. Thus, a standard meiosis II nondisjunction in the father does not produce an XY sperm: the X and Y were already separated in meiosis I.

For example, an XX sperm produced by paternal meiosis II fertilizing an ordinary X-bearing egg would give an XXX conception, not XXY. A YY sperm fertilizing that egg would give XYY. An O sperm fertilizing an X-bearing egg would give XO.

Routes that can produce an XXY conception

Two familiar nondisjunction routes can supply the extra X or Y combination:

1. Paternal meiosis I nondisjunction: If the father’s X and Y fail to separate in meiosis I, a sperm can receive both. An XY sperm fertilizing a normal X-bearing egg can produce an XXY conception.
2. Maternal nondisjunction: An egg can receive two X chromosomes if the mother’s X chromosomes or their chromatids fail to segregate properly. Fertilization by a normal Y-bearing sperm can then produce an XXY conception.

There are also less common ways an XXY cell line can arise, including a chromosome-separation error after fertilization. Such events can result in a mixture of cell lines, called mosaicism. These are distinct from a single, ordinary paternal meiosis II nondisjunction event.

Common mistakes

• Confusing meiosis I with meiosis II: Meiosis I separates the paternal X from the paternal Y; meiosis II separates sister chromatids. An XY sperm is associated with an error that leaves both X and Y together, as in paternal meiosis I nondisjunction.
• Assuming every extra-sex-chromosome sperm can make XXY: An XX sperm plus an X egg makes XXX; a YY sperm plus an X egg makes XYY. The chromosomes in both gametes matter.
• Treating every XXY case as the same event: The same XXY chromosome count can arise from different parental or post-fertilization events. The karyotype alone does not establish which division had an error.

The practical check is to write down the sex chromosomes in each gamete before combining them. For a typical XXY conception, the combination must be XX + Y or XY + X—not XX + X or YY + X.