Birth defects are relatively common, with major anomalies occurring in approximately 3% to 4% of live births. More than 20% of infant deaths in the United States are directly attributable to birth defects. In addition to mortality, birth defects also cause long-term morbidity, including intellectual disability and physical dysfunction, that can limit the productivity of individuals. These long-term disabilities can have significant impact on individuals, families, healthcare systems, and communities.
The term dysmorphology was first used in the 1960s to refer to the study of abnormal physical features. This term is used today to encompass both the normal variation of physical traits as well as the abnormal physical features resulting from an aberrant developmental process. Experts in dysmorphology, called dysmorphologists, are trained to describe the appearance of anomalies (ie, the trait manifestations) and establish an etiologic hypothesis based on their pattern or characteristics.
The pathogenesis and clinical classification of birth defects are reviewed here. Using the knowledge of normal embryology and development, an experienced clinician is able to analyze the characteristics and patterns of birth defects to hypothesize a pathogenetic mechanism, ultimately leading to improved diagnosis and treatment as well as informed recurrence risk and natural history counseling.
PATHOGENESIS AND EPIDEMIOLOGY
Birth defects are structural abnormalities that are present at birth (often called congenital anomalies) and caused by either intrinsic or extrinsic factors during intrauterine life. Birth defects are the result of genetic factors, nongenetic factors, or a combination of both. Developmental genetics, including embryology, and knowledge of molecular pathways responsible for normal human development are essential background for a physician tasked with diagnosing a newborn with congenital anomalies.
BRIEF REVIEW OF EMBRYOLOGY AND DEVELOPMENTAL GENETICS
Development is a highly regulated, precise, and efficient process by which a fertilized ovum becomes a mature organism capable of reproduction. The information required for development is transmitted from parent to offspring via genes that encode signaling molecules, cellular receptors, transcription factors, enzymes, transport systems, and other proteins tasked to ensure a highly regulated series of events that can be replicated with high fidelity. Each genetic program is expressed in a spatially and temporally overlapping pattern such that it can be used repetitively to control different developmental processes. The same gene program is reused in different tissues and at different times during development, increasing efficiency and decreasing the overall amount of genetic instruction passed from one generation to the next. Mutations in the genes mediating development are a common cause of birth defects.
Pattern formation is the process by which cells acquire different identities based on their relative spatial position within an embryo. The animal body plan is laid down during embryogenesis resulting in the formation of semi-autonomous regions, each of which undergo subsequent pattern formation to form organs and appendages. The hierarchical order of steps ...