Chromosomal Differences and Genetic Conditions

CHROMOSOMAL DIFFERENCES AND GENETIC CONDITIONS

Differences in the number or structure of chromosomes are a major cause of birth defects, mental retardation, and malignancies. Chromosomal differences are present in approximately 1 in every 160 live-born infants and are the cause of greater than 50% of all spontaneous first-trimester pregnancy losses (Lashley, 1998; Thompson et al., 2001). Chromosomal differences most com-monly involve an extra or missing chromosome. This is called ane-uploidy. Whenever there is an extra or missing chromosome, there is always associated mental or physical disability to some degree.

Down syndrome, or trisomy 21, is a common chromosomal condition that occurs with greater frequency in pregnancies of women who are 35 years or older. A person who has trisomy 21 Down syndrome has a complete extra number 21 chromosome, which causes a particular facial appearance and increased risk for congenital heart defects, thyroid and vision problems, and mental retardation. Other examples of chromosomal differences include trisomy 13 and 18, both more severe than Down syn-drome, and conditions involving extra or missing sex chromo-somes (eg, Turner syndrome, in which females have only one X chromosome instead of the usual two) (Lashley, 1998).

Chromosomal differences may also involve a structural re-arrangement within or between chromosomes. These are less common than chromosomal conditions in which there is an extra or missing chromosome, but occur in 1 in every 500 newborns (Thompson et al., 2001). People who carry “balanced” chromo-some rearrangements have all of their chromosomal material, but it is rearranged. A person who carries a balanced chromosomal re-arrangement has an increased risk for spontaneous pregnancy loss and for having children with an unbalanced chromosomal arrange-ment that may result in physical or mental disabilities. Known carriers are therefore offered prenatal counseling and testing.

Chromosome studies may be needed at any age, depending upon the indication. Two common indications are for confirma-tion of a suspected diagnosis such as Down syndrome, and for a his-tory of two or more unexplained pregnancy losses. Chromosome studies are accomplished by obtaining a tissue sample (eg, blood, skin, amniotic fluid), preparing and staining the chromosomes, and analyzing them under a microscope. The microscopic studyof chromosomes is called cytogenetics and is an area that is rapidly evolving. Today, cytogenetics is used with new molecu-lar techniques such as fluorescent in situ hybridization (FISH), which permits more detailed examination of chromosomes. FISH is useful to detect small abnormalities, including characterizing chromosomal rearrangements (Thompson et al., 2001).