The clinician involved in the care of children with congenital anomalies must possess a basic understanding of embryogenesis, limb formation, and inheritance patterns. The sequencing of the human genome and investigation into the molecular basis of limb development have provided new information regarding the causes of limb malformation. Advances in genomic and proteomic research have outlined the relationship between underlying gene(s) abnormalities and limb malformation. Genetic evaluation is quickly becoming part of the standard evaluation. In the future, genetic manipulation may prevent certain limb deformities and offer hope to families afflicted with genetic idiosyncrasies.

Embryogenesis of the upper extremity refers to formation of the limb 4 to 8 weeks after fertilization. The majority of upper extremity congenital anomalies occur during this 4-week period of rapid limb development. Limb bud development is initiated by outgrowth of the underlying mesoderm along the axis of the embryo into the overlying ectoderm. A thickened layer of ectoderm (apical ectodermal ridge) condenses over the limb bud and acts as a signaling center to guide the underlying mesoderm to differentiate into appropriate structures. The limb develops in a proximal to distal direction and the apical ectodermal ridge (AER) is responsible for this process. Loss of the AER during embryogenesis results in limb truncation and congenital amputation (Fig. 1). The AER also secretes proteins that influence the development of the underlying tissues. As the hand develops, the AER fragments around the hand paddle, which results in longitudinal interdigital necrosis between the digits. Failure of the AER to separate is the most prevalent explanation for syndactyly.