Birth defects, or congenital malformations, are the faulty formation of structures or body parts present at birth. Sporadic, hereditary, or acquired defects may be immediately observed or may become manifest later in life; they may be visible on the body surface or present internally. Birth defects may be life threatening and require surgical correction, or they may interfere with function or appearance. It is estimated that about 3% of all children are born with major defects; minor defects or variations are estimated to occur in 10% to 15% of births. Malformations may be single or multiple. Multiple malformations that occur in a regular recognizable pattern are referred to as syndromes–for example, the FETAL ALCOHOL SYNDROME sometimes observed in infants of mothers who drank heavily when pregnant. Birth defects may result from the action of genes, chromosomes, or the environment on the developing fetus, but often the cause cannot be determined. Inherited Defects Abnormal genes cause a significant number of different birth defects. Some can be identified as a single-gene disorder that is inherited in a simple Mendelian mode, that is, either a dominant or a recessive pattern.
For example, lobster claw deformity of the hands and feet (split hands or feet) is inherited and results from the effect of a single dominant gene. A person who has this deformity runs a 50% risk (1 in 2) of bearing offspring who will inherit the gene and will therefore also be affected. Autosomal recessive inheritance and X-linked recessive inheritance account for the other forms of single-gene inheritance that cause birth defects. In cases of autosomal recessive inheritance, both parents are normal but each carries a silent, or recessive, gene that, if matched in an offspring, causes the birth defect.
Because both parents are so-called carriers (heterozygotes) of the same abnormal gene, they run a 25% risk (1 in 4) of having a child with the birth defect caused by that particular gene. Examples of birth defects inherited in this autosomal recessive manner are TAY-SACHS DISEASE and SICKLE-CELL ANEMIA. In cases of X-linked recessive inheritance the abnormal gene is located on the X chromosome. The normal mother has two X chromosomes, one of which carries the gene for the abnormal condition; but if her son inherits her X chromosome with the abnormal gene, he will be affected with the condition.
HEMOPHILIA is inherited in this matter. Multifactorial Defects Many common birth defects do not occur in a pattern that indicates simple Mendelian inheritance. They seem to result from an interaction of genes and the environment, including the intrauterine environment, and each factor includes a number of different hereditary and environmental influences; hence, these defects are called multifactorial. Among them are congenital heart disease; neural tube defects, including SPINA BIFIDA, myelomeningocele, and anencephaly; and CLUBFOOT, CLEFT LIP AND PALATE, and dislocated hips. Chromosome Number An increase or decrease in the total chromosome material can cause birth defects. For example, the additional chromosome material in DOWN’s SYNDROME (mongolism) caused by an extra chromosome, number 21, is responsible for the characteristic mental retardation, short stature, and facial appearance. The gain or loss of chromosome material may involve a partial or entire chromosome. The specific birth defects that occur depend on the chromosome involved as well as on the amount of loss or gain of chromosome material.
Environmental causes of birth defects include teratogenic (literally, “monster-making”) agents and physical abnormalities in the mother’s uterus. Certain medications and chemicals as well as alcohol have been suggested causes of birth defects. It is difficult to establish definitive proof of a drug’s teratogenic action, and most available information is based on available animal studies and case reports of malformed children whose mothers all took a certain medication. Nutritional deficiencies and medical illnesses such as diabetes in the mother can also be viewed as contributing to an increase in malformations. Physical abnormalities in the mother’s uterus can contribute to birth defects such as dislocated hip and a clubfoot. In some cases uterine abnormalities may be the primary cause, but they are generally thought to play a contributory role and be distinct from the basic cause of the birth defect.
Prenatal Detection Currently, birth defects due to chromosome abnormalities, some inborn errors of metabolism, and a very few other disorders, including spina bifida and anencephaly, may be detected in the fourth month of pregnancy by a procedure known as AMNIOCENTESIS. This consists of withdrawing a small amount of amniotic fluid and analyzing it for the specific defect for which the pregnancy is at risk. Another procedure used to detect chromosomal problems, called chorionic villi sampling (CVS), was developed in China in the early 1970s and was being used experimentally in the United States beginning in the 1980s. It involves the use of a catheter to withdraw a sample of the chorionic villi, a tissue that surrounds the fetal sac. Marylou Buyse
Garell, Dale C., and Snyder, Solomon H., eds., Birth Defects (1989); Jones, Kenneth L., Smith’s Recognizable Patterns of Human Malformation, 4th ed. (1988); Pergaud, T. V., Environmental Causes of Human Birth Defects (1990).