Medical Genetics Health Article

MEDICAL GENETICS

Public health and medical genetics are strongly linked. The applications of both begin at preconception, when folic acid supplementation can be used to reduce birth defects, and continue through pregnancy, when testing is often done to detect abnormalities. At birth, screening of newborns for biochemical disorders enables the prevention of morbidity associated with diseases such as phenyl-ketonuria. The use of genetic screening for disorders expressed at older ages is expanding as a result of advances in molecular biology and cancer monitoring. With knowledge of the human genetic code, there will be acceleration in the diagnosis and treatment of genetic conditions and, consequently, the need for its incorporation into public health.

CLASSIFICATION OF GENETIC DISORDERS

The types of genetic disorders that may occur in any population can be classified into five categories:

1. Chromosome disorders are caused by the loss, gain, or abnormal arrangement of one or more chromosomes. Their frequency in the population is about 0.2 percent. Examples include Down syndrome and Turner's syndrome.
2. Mendelian disorders come from the mutation of a single gene. The transmission pattern is divided further into autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive. The frequency is about 0.35 percent.
3. Multifactorial disorders involve interactions between genes and environmental factors. The nature of these interactions is poorly understood. The risks of transmission can be estimated empirically, and the estimated frequency in the population is about 5 percent. Examples include cleft lip and neural tube defects.
4. Somatic genetic disorders are not inherited but occur after conception. They often give rise to malignancies and involve environmental and genetic influences.
5. Mitochondrial disorders arise from mutations in the genetic material in mitochondria. Mitochondrial DNA is transmitted only through the maternal line. These conditions are rare.

CHROMOSOME DISORDERS

Down Syndrome. The most frequent chromosome disorder (1 in 800 births in the United States) is the one associated with Down syndrome (also called Down's syndrome or trisomy 21). A common cause of mental retardation, Down syndrome is caused, in most instances, by an extra chromosome being segregated in an egg during development. The event is random. Another cause (3 to 4% of cases) is a robertsonian translocation, in which chromosome 21 attaches to another chromosome. In this case, although the amount of genetic material is normal, the number of chromosomes is 45 instead of 46. The offspring of a parent with a robertsonian translocation have a 25 percent chance of having Down syndrome. Accordingly, karyotyping (the examination of chromosomes) is required for all children born with Down syndrome.

Down syndrome can be diagnosed during the prenatal period with amniocentesis and chorionic villous sampling. These tests involve obtaining either amniotic fluid or a sample from the placenta. Risks for Down syndrome increase with robertsonian translocation and previous birth of a child with Down syndrome; increasing maternal age; and low serum levels of maternal alpha ([.alpha])-fetoprotein (because the liver of a fetus with Down syndrome is immature, [.alpha]-fetoprotein levels are lower than normal). Further risk for Down syndrome can be ascertained by measuring the serum levels of [.alpha]-fetoprotein, estrogen, and human chorionic gonadotropin (hCG) in the blood.

Turner's Syndrome. Turner's syndrome is a disorder of growth and development occurring in about 1 in 2,000 births. The syndrome involves errors in one of the X chromosomes and is often associated with heart defects, osteoporosis, infertility, and short stature. Diabetes, hypothyroidism, and congenital urinary-tract abnormalities are also more common among patients with Turner's syndrome (35 to 70%) than in the general population. Edema before birth may cause webbing of the neck, a low posterior hairline, and ear abnormalities.

Klinefelter's Syndrome. Klinefelter's syndrome, characterized by a 47, XXY karyotype, is a disorder of growth and development, occurring in about 1.7 per 1,000 male infants. The disorder usually is diagnosed at puberty or during an infertility evaluation. In adolescents, its characteristics include gynecomastia (40%), small testicles, tall stature, and an arm span that is greater than the person's height. Klinefelter's syndrome is the most common cause of hypogonadism in males, and testosterone levels are about half the normal value, while follicle-stimulating hormone and lactate dehydrogenase levels are increased. Treatment includes testosterone, and occasionally mastectomy for gynecomastia.