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Major congenital anomalies, common genetic syndromes.


To review the approach to the evaluation and management of major congenital anomalies that often present to the neonatal intensive care unit.


Congenital anomalies, also referred to as birth defects, are present in 2−3% of liveborn births. Major congenital anomalies are those that have a substantial impact on health or cosmetic appearance (such as critical congenital cardiac defects, cleft lip and palate, or absence of a limb) and are not on the spectrum of normal variation within a population, while minor congenital anomalies are relatively common and do not affect the health of the individual (such as an ear tag, a supernumerary nipple, or a single palmar crease). The neonatal intensive care unit (NICU) is enriched for infants with these conditions due to the potential that many have to impact survival after birth. Indeed, prior literature has shown that congenital anomalies are responsible for 25−50% of mortality in the NICU setting, and birth defects, along with chromosomal anomalies, are the most common cause of infant deaths in the United States.

The underlying etiology of congenital anomalies may be environmental or genetic, with environmental causes including teratogenic exposures such as to thalidomide or excessive alcohol consumption in addition to exposures to maternal conditions, as seen in diabetic embryopathy. Genetic causes of congenital anomalies are quite diverse and may include chromosomal aneuploidy syndromes, such as trisomies 13, 18, and 21, chromosomal microdeletion or duplication syndromes, such as 22q11 deletion syndrome or Cri-du-Chat (5p deletion) syndrome, in addition to monogenic disorders such as CHARGE (coloboma, heart defects, atresia choanae, retarded growth, genitourinary anomalies, ear abnormalities) syndrome, caused by pathogenic variants in single genes. It is important to recognize which infants are at higher risk for genetic syndromes, as testing may be available for these conditions. Multiple developmental mechanisms can be responsible for congenital anomalies, including malformation, deformation, and disruption. A malformation is the abnormal development of an embryonic tissue due to intrinsic factors, such as a congenital heart defect. A deformation is an abnormally formed structure due to mechanical forces (without which the structure would appear normal), such as the flattened face seen in Potter sequence. Disruptions are defects occurring when normal tissue is damaged or interrupted, as in amniotic band sequence. It is helpful to distinguish between these types of congenital anomalies, as deformations and disruptions are less likely to be related to genetic causes than malformations.

Furthermore, while the majority (75%) of major anomalies are isolated, they can occur together in an association, a sequence, or as a syndrome. An association is a group of anomalies that tend to occur together (more often than would be expected by chance) such as VACTERL (vertebral, anal, cardiac, tracheoesophageal fistula, renal, and limb defects) association. Occasionally, greater ...

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