Birth Defects

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 Factors 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
Bibliography: Garell, Dale C., and Snyder,
Solomon H., eds., Birth Defects (1989); Jones,
Kenneth L., Smith\'s Recognizable