congenital anomaly A physical abnormality
present at birth. Congenital anomalies, also called
BIRTH DEFECTS, can affect nearly any structure in
the body and may be hereditary or random.
GENETIC DISORDERS and exposure to teratogens
(substances, such as drugs, that alter the develop-
ment of the embryo or fetus) account for the
majority of congenital anomalies. The symptom
constellations that characterize CHROMOSOMAL DIS-
ORDERS typically contain multiple congenital
anomalies.
Some congenital anomalies are almost always
treatable, such as atrial septal defect (an abnormal
opening in the septum, or wall, between the two
atria in the HEART) or CLEFT PALATE/CLEFT PALATE AND
LIP(failure of the oral structures to properly close).
Other congenital anomalies are life-altering or
life-threatening, such as severe forms of SPINA
BIFIDA(in which the spine fails to form properly)
or transposition of the great arteries (incorrect
alignment of the major BLOODvessels in the heart).
Many congenital anomalies are physically
apparent at birth or manifest symptoms that
reveal their presence. An infant born with con-
genital anomalies of the heart, for example, may
have a bluish hue to the SKIN(CYANOSIS) that indi-
cates insufficient oxygen to the tissues. The diag-
nostic path may include imaging procedures such
as ULTRASOUND, COMPUTED TOMOGRAPHY (CT) SCAN,
andMAGNETIC RESONANCE IMAGING(MRI) that allow
the neonatologist to visualize and identify the
anomaly. GENETIC TESTINGmay also be appropriate,
depending on the nature of the anomaly. Treat-
ment depends on the type, extensiveness, and
complexity of the anomaly. Surgeons often can
easily repair isolated anomalies, such as cleft lip or
atrial septal defect, with minimal or no residual
consequences. Extensive or multisystem anom-
alies may not be treatable.
See also CONGENITAL HEART DISEASE;HORSESHOE
KIDNEY; REPLICATION ERROR.
cystic fibrosis An inherited genetic disorder
resulting from multiple mutations of the cystic
fibrosis transmembrane conductance regulator
(CFTR) GENEon CHROMOSOME7, inherited as auto-
somal recessive mutations. Researchers believe as
many as 10 million people may be cystic fibrosis
carriers and unaware of it. Though researchers
know of approximately 600 CFTR mutations, one
MUTATION, called the delta F508 mutation, accounts
for about 70 percent of cystic fibrosis in the United
States. About 30,000 Americans live with cystic
fibrosis.
CFTR is a protein that, when functioning nor-
mally, facilitates the transport of chloride and
other ions across cell membranes. In cystic fibrosis
the presence of CFTR is greatly diminished and
salts fail to properly cross the cell membranes.
One result is very high concentrations of salts in
the sweat, particularly chloride, giving the SKINa
salty taste. The effect of diminished CFTR is most
pronounced on epithelial secretory cells—the cells
that form mucous membranes and make up the
linings of the intestinal tract, LUNGS, and urinary
system, which rely on sodium chloride and other
salts to draw fluid into their secretions. Without
CFTR the normal watery secretions of these cells
become thick and sticky.
Cystic fibrosis most seriously affects the pul-
monary and gastrointestinal systems, and does so
in all people who have the disorder, though the
disorder involves all body systems to varying
extents. Thickened secretions accumulate in the
airways in the lungs, creating obstructions that
interfere with BREATHINGas well as establish breed-
ing grounds for BACTERIA and other pathogens.
Furthermore, the high chloride content on the
surface of the epithelial cells that line the
bronchial structures suppresses the body’s natural
bacterial-control mechanisms. People who have
cystic fibrosis have frequent or chronic upper res-
piratory infections and pneumonias. About 85
percent of people who have cystic fibrosis also
develop pancreatic insufficiency, in which the
DIGESTIVE ENZYMESthe PANCREASnormally secretes
do not adequately support digestion.Symptoms and Diagnostic Path
Infants who have cystic fibrosis may have MECO-
NIUMileus at birth, an obstruction of the bowel
with meconium, a tarry substance that normally
passes from the RECTUMwithin a few hours of
birth. Other signs and symptoms of cystic fibrosis
may emerge at any time and include- large, foul-smelling, greasy-looking stools
- frequent bowel blockages
120 Genetics and Molecular Medicine