The problem with the gene pool is there is no lifeguard.


Hereditary diseases are the result of a person’s genetic makeup. It is uncertain to what extent environmental factors influence the course of a hereditary disease, but the two do interact. Hereditary diseases do not always appear at birth. Mild hemophilia (ICD-9: 286.0) and muscular dystrophy (ICD-9: 359.1) may go undetected until adolescence or adulthood.

Thousands of genetic diseases are identified in humans—some are fatal. All genetic information is contained in DNA, a complex molecular structure found in the nucleus of cells. The DNA itself is incorporated into structures called chromosomes. The normal number of chromosomes in humans is 46 (23 pairs). In the formation of the ovum and sperm cells (sex cells, or gametes), this number is reduced by half, with each gamete having 23 chromosomes. When the two sex cells unite at the time of fertilization, the 23 chromosomes from the ovum combine at random with the 23 chromosomes from the sperm, producing a cell with a full complement of 46 chromosomes. Two of these chromosomes determine sex.

A gene is the basic unit of heredity. Each gene consists of a fixed segment of the DNA on a specific chromosome. Physical traits are the result of the expression of pairs of genes. Gene pairs are homozygous when they possess identical genes from each parent for a particular trait and when they are both dominant (one parent contributes) or both recessive (both parents contribute) in their expression of a trait. Gene pairs are heterozygous when they possess different genes from each parent for a particular trait and if one gene is dominant and one is recessive. Recessive genes are expressed only when the gene pair is homozygous, whereas dominant genes are expressed whether the gene pair is homozygous or heterozygous.

When trying to determine genetic makeup, a family history is taken to determine a person’s genotype, which is a description of the combination of a person’s genes with respect either to a single trait or to a larger set of traits. Genotype includes all of the genes that are inherited from one’s parents. The phenotype consists of the observable physical characteristics, determined by the combined influences of a person’s genetic makeup and the effects of environmental factors. Phenotype is revealed in a person’s appearance—the color and texture of the hair, shape of the nose, height, and so on.

A sex-linked hereditary disease can occur when one parent contributes a defective gene from the sex chromosome. In color blindness (ICD-9: 368.5x), the inability to distinguish reds from greens is the result of a recessive gene located on the X chromosome. The trait shows up when there is no dominant gene for normal color vision to override the recessive gene.

Changes in the structure of genes, called mutations, may cause disturbances in body functions. Mutations occur when the normal sequence of DNA units is disrupted. How such a disruption is manifested depends on whether the affected gene is dominant or recessive and on whether it is homozygous or heterozygous. The causes of mutations are largely unknown, but they could be the result of environmental factors, such as exposure to certain chemicals or radiation.

Classification of Hereditary Diseases

Genetic diseases are the result of monogenic (Mendelian) alterations, chromosome aberrations, and multifactorial errors, and are classified similarly.

Monogenic (Mendelian) Disorders

Monogenic disorders are those caused by mutation in a single gene. The way in which the disorder is passed on to succeeding generations (the pattern of inheritance) is determined by whether the gene is dominant, recessive, or sex-linked. (A sex-linked gene is carried on the X chromosome. Because males have only one X chromosome, a sex-linked gene will be expressed in males whether it is dominant or recessive.) Figure illustrates the three most common patterns of inheritance of monogenic disorders. Examples ofmonogenic disorders are described below.

Patterns of inheritance monogenic disorders

FIGURE. Patterns of inheritance monogenic disorders.

A. Pedigree displaying autosomal dominant inheritance. Autosomal dominant traits can be inherited by either gender. The female individual I-1 is heterozygous autosomal dominant. If she were homozygous for the mutant trait, then all progeny in generation II would show the trait.

B. Pedigree displaying autosomal recessive inheritance. Autosomal recessive traits can be inherited by either gender. A recessive allele needs to be inherited from both the mother and the father for the trait to be seen. Recessive traits may not be seen for several generations, as shown by the progenies III-3 and III-4 who received both alleles.

C. Pedigree showing sex-linked inheritance. The male gender is most often affected by sex-linked disorders due to a mutation on the X chromosome. The II-3 male is affected, so his mother, individual I-1, must have been a carrier. The female individuals II-2 and III-3 both had a son with the trait, so both are carriers. Notice that the female individual III-1 had progeny with a male that carries the mutant trait. The female progeny IV-1 shows the trait because she inherited two mutant X chromosomes, so III-1 must also be a carrier.

Autosomal Dominant

Only one abnormal gene from a parent is needed for a disease to be inherited. One parent often has the disease. When one parent has the faulty gene, there is a 50% chance the offspring will have the defect. Examples of autosomal dominant diseases are identified here.

  • Huntington disease (ICD-9: 333.4): A disorder causing the degeneration of brain neurons in certain areas of the brain. Individuals show signs of uncontrolled movements, emotional disturbances, and mental deterioration. Symptoms often do not develop until middle age. It is also called Huntington chorea. Tetrabenazine (Xenazine) is the first medication to be specifically approved by the Food and Drug Administration for the treatment of the signs or symptoms of Huntington disease. This medication can reduce the jerky, involuntary movements of the disease by increasing the amount of dopamine available in the brain.
  • Retinoblastoma (ICD-9: 190.5): A rare eye tumor that develops in the retina; it is usually present at birth and tends to occur in both eyes. The cancer can spread to other areas of the body. Treatment is varied, partially dependent on the spread of the disease, but removal of the eye may be necessary.

Autosomal Recessive

There must be two copies (both parents) of the abnormal gene in order for an autosomal recessive disease or trait to develop. Some examples follow.

  • Cystic fibrosis: A chronic, generalized disease of the glands that release their secretions into the digestive tract or to the outer surface of the body, or exocrine glands, primarily affecting the pancreas, respiratory system, and sweat glands.
  • Tay-Sachs disease (ICD-9: 330.1): This disease is a rare lipid abnormality in which harmful amounts of fatty substances build up in the brain cells. It is distinguished by progressive neurological deterioration and a cherry-red spot with a gray border on both retinas. It chiefly affects infants of eastern European Jewish (Ashkenazi) ancestry, resulting in deafness, blindness, and paralysis. Recurrent bronchopneumonia is a problem after age 2. Death usually occurs by age 5.
  • Phenylketonuria (PKU): A rare inherited disease caused by an inability to metabolize phenylalanine, an essential amino acid. Amino acids are organic compounds that constitute the primary building blocks of proteins. Mental disability results unless a special diet begins within the first few weeks of life.
  • Sickle cell anemia: A disease affecting mostly black populations around the world. It is one of the most common single-gene disorders. It occurs because the body produces a defective form of hemoglobin causing red blood cells to roughen and become sickle shaped when deoxygenated. These cells clump together, making it difficult for them to pass through blood vessels.

X- or Sex-Linked

Dominant X-linked diseases occur when a single abnormal gene on the X chromosome can cause a disease; this abnormal gene dominates the gene pair. There are only a few known dominant X-linked diseases. Two identified here are vitamin D–resistant rickets and Rett syndrome.

  • Vitamin D–resistant rickets (ICD-9: 275.3): This disease is defined as such because it is resistant to the vitamin D treatment usually given for rickets and is evidenced by deficient amounts of mineral in the cartilage growth plates and osteomalacia, or softening of the bones.
  • Rett syndrome (ICD-9: 330.8): This is a severe disorder affecting the way the brain develops. It occurs most frequently in girls, producing symptoms similar to autism. Children with Rett syndrome have problems with motor functions that affect their ability to speak, walk, chew, use their hands, and even breathe. They may need a feeding tube in order to get sufficient dietary nutrients. Recessive X-linked diseases occur when both the gene pairs are abnormal. If only one gene in the pair is abnormal, the disorder is quite mild or does not show at all. The two identified here are hemophilia and Duchenne muscular dystrophy.
  • Hemophilia: A rare bleeding disorder caused by a deficiency of specific types of serum proteins called clotting factors. A person with hemophilia bleeds longer following any kind of injury because the blood does not clot normally. Hemophilia can be mild, moderate, or severe depending on how much clotting factor is in the blood.
  • Duchenne muscular dystrophy: A progressive bilateral wasting of skeletal muscles in males. Symptoms appear between ages 2 and 5 and include difficulty walking. The child has a stumbling gait and falls easily.

Chromosomal Disorders

Chromosomal disorders are caused by abnormalities in the number of chromosomes or by changes in chromosomal structure, such as additions (more than necessary), deletions (missing genes), or translocations (genes shifted from one chromosome to another or to a different location on the same chromosome).

Diseases caused by chromosomal alterations include the following:

  • Klinefelter syndrome (ICD-9: 758.7): A condition that occurs when there is an additional X chromosome in males. The male body shape is elongated, the testes are small, the mammary glands are abnormally large, and men with this syndrome do not produce sperm.
  • Turner syndrome (ICD-9: 758.6): A condition caused by the loss of or an incomplete X chromosome in either the ovum or the sperm. This syndrome, affecting girls, is often characterized by shortened stature; swollen hands and feet; and coarse, enlarged, prominent ears. Most are infertile.
  • Trisomy 21 or Down syndrome: A condition in which an individual has three number 21 chromosomes instead of the normal two. The condition is more likely to occur in children born to parents ages 35 to 50. Infants with this condition typically have a sloping forehead and folds of skin over the inner corners of their eyes, and they may have heart defects. They generally show evidence of moderate to severe mental disability. This condition is one of the most common birth defects.

Multifactorial Disorders

Multifactorial disorders result from the interaction of many factors, both hereditary (mutations in multiple genes) and environmental. Among the multifactorial diseases are the following:

  • Diabetes mellitus: A disorder of carbohydrate, fat, and protein metabolism. The disease is due primarily to insufficient insulin production by the pancreas.
  • Congenital heart anomalies: This category includes six major anatomic defects that change the blood flow through the heart, causing circulatory problems.