Genetic disorders and birth defects are sometimes perceived as
being so uncommon that the general pediatrician will seldom encounter them.
However, each day more than 400 babies with birth defects are born
in the United States, and 1 of every 5 infant deaths is caused by
these disorders. Virtually every medical condition, except for some
cases of trauma, is influenced by an individual’s genetic
background. Rapid advances in our knowledge of the genetic basis of
disease, coupled with emerging technologies for high-throughput
genetic testing, are also rapidly transforming the practice of medicine.
Comprehensive databases of factual information about the identification
of new disease genes, genotype–phenotype correlation, and the
availability of genetic testing have become widely available online
and in published review articles. Thus, each of the following sections
seeks to emphasize important fundamental concepts while providing paradigmatic
Traditionally, various human traits (eg, skin color, intelligence)
and disorders (eg, phenylketonuria, achondroplasia) have been divided
into those that are genetic versus those that are nongenetic, the
latter usually referring to disorders “determined” by
the environment (eg, infectious diseases, teratogens). However, this
dichotomy separating gene and environment is largely artificial,
and the distinction between the two has become increasingly blurred.
Disorders caused by mutations in a single gene (eg, cystic fibrosis,
sickle-cell disease) can be heavily influenced by the environment, and
diseases caused by the environment (eg, AIDS secondary to infection
with HIV-1) can be substantially modified by the presence of certain polymorphisms.
In other words, the cause of most diseases can be considered genetic
and environmental; some diseases are more strongly influenced by
genes, whereas others are more strongly influenced by the environment.
Whether defined narrowly or broadly, genetic disorders and birth
defects contribute substantially to morbidity and mortality in pediatric
patients. For example, the percentage of deaths attributable to
genetic disease in hospitals in the United Kingdom has risen from
16.5% in 1914 to 50% in 1976. Birth defects are
also the leading cause of death in infancy in the United States,
accounting for more than 20% of infant deaths. Cardiovascular
malformations are the leading cause of premature mortality from
congenital anomalies. This reflects a better understanding of the
etiology of pediatric diseases as well as the substantial reduction
in infectious disease and perinatal mortality during the 20th century.
Population-based studies suggest that birth defects and genetic
disorders account for about 10% of hospitalizations and
about 30% of all hospitalization charges. Approximately
7% of pediatric admissions are for single-gene and chromosomal
disorders, and another 15% to 20% for congenital
malformations of different types. Moreover, about 35% of
hospital deaths of children are caused by a genetic condition and/or
birth defect. Recent advances in therapeutics have substantially
prolonged the survival of children with birth defects and/or
genetic diseases, challenging practitioners to care for older children
and young adults with genetic disorders.
Classifications of genetic disorders depend, in part, on the
delineation of a phenotypic trait (eg, ...