Genetic Diseases

There are several different categories of genetic diseases that are divided by the type of gene or chromosome that transmits the disease.

Autosomal Recessive Diseases

In most cases, a woman who inherits a defective recessive gene from one parent and a normal dominant gene from the other parent does not exhibit any symptoms of that illness but is a carrier of that abnormal gene. However, if she has children with a man who is also a carrier, their children have a 50 percent chance of inheriting one defective gene and being nonsymptomatic carriers, and a 25 percent chance of inheriting two defective recessive genes and expressing the disease. This pattern is called autosomal recessive inheritance. The better-known of these disorders include sickle cell anemia, Tay-Sachs disease, and cystic fibrosis.

Sickle cell anemia: Anemia is sometimes caused by a deficiency of hemoglobin. Hemoglobin is the substance in red blood cells that carries oxygen to the other cells in the body. In sickle cell disease, the hemoglobin is abnormal. People who carry only one defective recessive gene usually have no symptoms of the disease. People who inherit two sickle cell genes develop many problems due to the structure of their abnormal hemoglobin.

This defective hemoglobin molecule causes the normally round blood cell to sickle (assume a crescent shape). Anemia occurs because sickled red blood cells are more fragile, hence more easily destroyed. Sickled cells are also less able to bend as they squeeze through tiny blood vessels. Thus, these cells become trapped and obstruct small vessels.

Episodic clogging of the vessels with sickled blood cells causes tissue damage and pain, especially in the hands, feet, joints, and abdomen. Children with sickle cell anemia are prone to more frequent infections than children without the condition.

At present, no cure for sickle cell anemia exists. Treatment includes administration of painkillers and antibiotics as necessary. Children with sickle cell anemia who develop a fever should be seen by their doctor as soon as possible to determine treatment, which may include hospitalization for intravenous fluids and antibiotics. More children with sickle cell anemia are surviving into adulthood because of improved therapy and new, effective vaccines for many illnesses. Such vaccines are vital because children with sickle cell anemia are at increased risk for certain bacterial infections.

Because sickle cell anemia is most common among black persons, black adults are encouraged to undergo screening to determine if they are carriers of sickle cell anemia. Carriers can be identified by means of a simple blood test. Approximately eight percent of black people in the United States are carriers.

If both parents are carriers, they have a one in four chance of giving birth to a child with sickle cell disease. Sickle cell disease can be diagnosed before birth with the use of amniocentesis (see page 14 for an explanation of this procedure). In many states, most newborn babies are screened for sickle cell disease at birth by means of a blood test.

Tay-Sachs disease: Tay-Sachs disease is a metabolic disorder marked by the accumulation of a type of fatty acid in the liver, spleen, and brain. It is caused by a deficiency in the enzyme that normally degrades this fatty acid. After four to six months of normal development, children with Tay-Sachs exhibit deterioration in neurologic development. The disease progresses to mental retardation, blindness, and convulsions. Death usually occurs by age three or four. No treatment exists.

Preventive measures are available. The Ashkenazim, the Jews of eastern Europe, are disproportionately affected by Tay-Sachs, with nearly 100 times the rate of occurrence as other groups. Carriers have no symptoms of the disease and sometimes have no family history of the disease. It is recommended that all Jewish couples of eastern European descent undergo screening for the Tay-Sachs gene before they start their families. If both parents are carriers, diagnosis of Tay-Sachs disease in the baby can be made during pregnancy with the use of amniocentesis.

Cystic fibrosis: Cystic fibrosis is a serious childhood illness that causes the glands of the body to secrete abnormal sweat and mucus. The sweat glands secrete too much salt. The abnormally thick, sticky mucous secretions accumulate in and obstruct the lungs and pancreas. Since the pancreas is an important organ for digestion, these children fail to grow properly. The thick mucus in the lungs makes breathing difficult and leads to infections. Death is usually due to respiratory failure. Although no cure exists, improved treatment has brightened the prognosis of children with cystic fibrosis, giving them a good chance for survival into adulthood.

Cystic fibrosis is much more common in white people of northern European extraction. In the United States, approximately 1 in 29 white people are carriers. One infant in every 3,000 live births has cystic fibrosis. Traditionally, the disease has been diagnosed on the basis of sweat test results obtained only after the appearance of the symptoms. However, now diagnosis can be made before birth with amniocentesis.

Phenylketonuria: Phenylketonuria (PKU) is a rare disorder that can cause severe mental retardation. It is caused by an inability to convert an amino acid called phenylalanine into another amino acid called tyrosine. (Amino acids are the building blocks of proteins.) At elevated levels, phenylalanine damages brain cells, causing retardation.

In the United States, all newborns are screened for PKU by means of a blood test. Early detection and prompt treatment can prevent the mental retardation. Treatment consists of limiting a child's dietary intake of phenylalanine. If this dietary regimen is followed, children with PKU can have essentially normal development. Pregnant women who have PKU need to stick to this special diet to protect the baby's developing nervous system. All people with PKU must completely avoid the artificial sweetener aspartame, which contains phenylalanine. New research is in progress to help identify carriers of PKU and to diagnose PKU prenatally.

Autosomal Dominant Diseases

Another category of hereditary disease is called autosomal dominant disease. Because the defective gene is dominant, the disease is expressed even if only one gene is defective. A normal gene cannot mask the harmful effects of an abnormal gene as it can in autosomal recessive disease. If one parent has an autosomal dominant disease, the chances are 50 percent that each child will inherit the disorder.

Huntington chorea: An example of an autosomal dominant disease is Huntington chorea, a brain disease marked by abnormal body movements and mental deterioration beginning in middle age.

Although a few medicines have been found to make the symptoms more tolerable, the disease has no cure. Researchers have been able to identify carriers in families with Huntington chorea with a genetic test. It is hoped this procedure will be perfected and also extended to prenatal diagnosis.

Sex Chromosomes and Sex Determination

As previously stated, most cells in the body have 46 chromosomes, consisting of 22 pairs of autosomes and 2 sex chromosomes. The sex chromosomes determine whether a person is male or female. Women have two X chromosomes. Men have one X and one Y chromosome.

The sex cells (eggs and sperm) contain only 23 chromosomes -- 22 autosomes and 1 sex chromosome. Each ovum (egg) contains one X chromosome. Half of a man's sperm cells carry an X chromosome; the other half carry a Y chromosome. During fertilization, the genetic material of the egg and sperm unite to create the full complement of 46 chromosomes. If the ovum is fertilized by a Y sperm, the baby will be a boy; fertilization by an X sperm results in a girl.

X-Linked Recessive Diseases

In sex-linked inheritance, the gene responsible for the disease is located on the X chromosome. Usually, the abnormal gene is recessive. For these reasons, the resultant disorder is called an X-linked recessive disease. In a woman with such a defective gene, the effects of the abnormal gene are masked by those of the normal gene on the other X chromosome. Although she does not have the disease herself, she is a carrier, capable of transmitting the defective gene to her children.

In X-linked recessive disease, the Y chromosome lacks the corresponding normal gene to mask the harmful effects of the abnormal gene on the X chromosome. Thus, all male offspring of a woman who is a carrier of an X-linked recessive disease have a 50 percent chance of having the condition. All female offspring have a 50 percent chance of being carriers. Following are examples of X-linked recessive disorders:

Color blindness: A person with the most common form of color blindness cannot distinguish red from green hues.

Hemophilia: In hemophilia, the blood does not clot properly. Persons with hemophilia bleed excessively, even from minor cuts. There are several forms of hemophilia, each caused by a deficiency of a different protein called a clotting factor. The disease is managed by giving transfusions of the deficient clotting factor and of whole blood to replace blood losses. Research continues toward the accurate identification of carriers and prenatal diagnosis of this disease.

Duchenne muscular dystrophy: Muscular dystrophy refers to a group of rare diseases characterized by progressive muscular weakness. Duchenne type muscular dystrophy is the most common. Between the ages of two and six years of age, children with this condition develop weakness first in their legs, then in their arms and trunk. The weakness rapidly worsens. Most children die during their second decade, usually as a result of severe weakness of the muscles of respiration. The disease has no cure. Treatment includes physical therapy, braces, and, occasionally, surgery.

Newer techniques and better understanding of the genes involved have made prenatal testing possible. Advances in genetic testing are soon likely to make it possible to detect the recessive trait in carriers as well.

Multifactorial Genetic Diseases

Multifactorial genetic diseases are illnesses that tend to run in families. These diseases are not due simply to the inheritance of a single defective gene. Rather, a cluster of faulty genes is inherited, which predisposes the person to a disease. Given the appropriate environmental factors, the person may actually develop that disease. Examples of illnesses that run in families include such chronic adult diseases as coronary heart disease, high blood pressure, and stomach ulcers, as well as birth defects, such as cleft lip and palate and spina bifida.

Cleft lip and palate: In cleft lip, the upper lip is divided by a vertical fissure. In cleft palate, the roof of the mouth is split by a longitudinal fissure. These two birth defects can occur alone or together. They are the result of incomplete fusion of the components that form the lip and mouth during fetal development.

Spina bifida: Spina bifida is a failure in the closure of the bony vertebral column with or without protrusion of the nerve tissue of the spinal cord. Paralysis below the defect often accompanies spina bifida if the spinal cord does protrude. When the spinal cord does not protrude, the vertebral defect may go unnoticed. Clues to indicate the presence of this form of spina bifida are abnormalities of the skin and tufts of hair overlying the spine in the lower part of the back.

During pregnancy, spina bifida in the fetus can be diagnosed by means of ultrasound study and detection of elevated levels of a substance called alpha-fetoprotein in the mother's blood and in the amniotic fluid that bathes the fetus. Spina bifida can be caused by a folate deficiency in the mother during pregnancy or exposure of the pregnant woman to certain drugs that interfere with folate.

Chromosomal Abnormalities

Sometimes the structure or the number of chromosomes is not normal. The risk of having a child with chromosomal abnormalities increases with increasing maternal age (and to some extent with increasing paternal age as well). If chromosomal abnormalities occur in the sex cells (eggs and sperm), the offspring may have physical and mental disorders.

Down syndrome: Formerly called mongolism, Down syndrome is a condition caused by a chromosomal abnormality. Due to the failure of the chromosomes to divide evenly during cell division, the person with Down syndrome has an extra chromosome (a total of 47). The presence of this extra chromosome causes a characteristic physical appearance and delayed physical and mental development. Other ailments, such as defects in the heart and digestive system, can accompany this syndrome. Despite their disabilities, children with Down syndrome usually have pleasant dispositions and can do quite well if given special therapy.

The cause of the chromosomal abnormality leading to Down syndrome is unknown. A genetic predisposition may exist. The incidence of Down syndrome increases with increasing maternal age. The condition can be diagnosed prenatally with the use of amniocentesis. For these reasons, women who have previously given birth to a baby with a chromosomal abnormality or who are older than 35 years of age are encouraged to undergo amniocentesis.

Genetic Counseling

In recent years, tremendous progress has been made in the development of genetic tests to diagnose heritable diseases. You may wish to consult your physician about genetic counseling if any of the following risk factors apply to you:

You have a family history of a hereditary disease or of mental retardation of unknown origin.


You are a woman older than 35 years of age.


You have had a previous child with a chromosomal or other genetic disorder or any birth defects.


You have had three or more miscarriages or a stillbirth.
If you have any concerns or questions regarding heritable diseases, ask your physician. If you are considered to be at risk for passing on a hereditary disease to your children, you can receive genetic counseling. A genetic counselor asks you about your personal and family medical history. Blood tests may be necessary to help determine whether you are a carrier of a heritable disorder. You are advised about the chances of transmitting hereditary illness to your offspring.

If you are pregnant, the well-being of your fetus can be assessed by several procedures:

Ultrasound: High-frequency sound waves are used to produce images of the placenta and fetus. It can detect gross defects, especially of the heart, bones, brain, and spinal cord.


Amniocentesis: A small amount of amniotic fluid, the liquid that bathes the baby inside the uterus, is withdrawn and analyzed. Many genetic diseases can be diagnosed prenatally with the use of am-niocentesis.


Chorionic Villus Sampling (CVS): A few fetal cells from the chorionic villus, a part of the placenta, are withdrawn and analyzed for the presence of select diseases.


Fetoscopy: The fetus is directly observed within the uterus by means of special lenses. During fetoscopy, fetal blood can be sampled. It is rarely used today.


Radiography: X-ray films are occasionally obtained because they can depict certain skeletal abnormalities in the fetus.
Remember that the diseases described in this section are rare. Most expectant parents can look forward to the arrival of a healthy baby. If you are pregnant or hope to be and have any worries about the well-being of your child, don't hesitate to address them with your doctor.

If your child does have a hereditary disease, however, it's important to confront and accept the realities of this challenge. Keep the lines of communication open within your family, seek out support groups, and avoid bearing all the guilt for your child's disease.