Cell Division Abnormalities and Genetic Defects

Exam Tip: Nondisjunction errors are easily identifiable using a karyotype, which is a visual map of an individual's chromosomes.

Autosomal Nondisjunction

Autosomes are the non-sex chromosomes. When nondisjunction occurs in these chromosomes, the resulting zygote is often non-viable. In fact, there are only three specific autosomal trisomy situations where a fetus typically survives to birth; other autosomal errors usually result in spontaneous abortion.

Patau Syndrome (Trisomy 13)

Patau syndrome is caused by having three copies of chromosome 13. It occurs in approximately 1 in 15,000 births, and unfortunately, most affected infants do not survive past infancy.

Edward’s Syndrome (Trisomy 18)

Edward's syndrome results from trisomy of chromosome 18. It is slightly more common than Patau syndrome, occurring in about 1 in 6,000 births, though most cases also result in death during infancy.

Down Syndrome (Trisomy 21)

Down syndrome is the most common autosomal trisomy surviving to birth, caused by three copies of chromosome 21. It occurs in approximately 1 in 900 births.

A critical factor in Down syndrome is the maternal age at conception. The incidence of the syndrome increases significantly as the mother ages:

• Under age 30: 1 in 3,000 chance.
• Age 35: 1 in 365 chance.
• Age 48: 1 in 9 chance.

Nondisjunction of Sex Chromosomes

Unlike autosomal errors, nondisjunction involving the sex chromosomes (X and Y) often allows for survival into adulthood, though it results in distinct clinical syndromes.

Female Sex Chromosome Abnormalities

When nondisjunction affects the X chromosomes in females, several outcomes are possible:

• Turner Syndrome: This is a case of monosomy, where the individual has only one X chromosome (XO).
• Trisomy X: The individual has three X chromosomes (XXX).

Male Sex Chromosome Abnormalities

In males, nondisjunction can lead to several different chromosomal combinations:

• Klinefelter Syndrome: Occurs when a male has an extra X chromosome (XXY).
• XYY Syndrome: Occurs when a male has an extra Y chromosome (XYY).

Other Chromosomal Alterations

Beyond changes in the number of chromosomes, mutations can also involve the structure of the chromosomes themselves. While gene mutations involve small changes like insertions or deletions of single bases, chromosomal mutations involve much larger segments of DNA.

Common structural alterations include:

• Deletions: A portion of the chromosome is lost. An example is DiGeorge’s syndrome, which involves a deletion at 22.q.11.
• Duplications: A segment of the chromosome is repeated.
• Inversions: A segment of a chromosome breaks off and reattaches in reverse order.
• Translocations: A segment of one chromosome breaks off and attaches to a different, non-homologous chromosome.