Classification and developmental biology of congenital anomalies of the hand and upper extremity.

Congenital anomalies of the hand and upper extremity are classified according to appearance; thus, the myriad of disparate presentations are organized into groups that share common morphologic features. The primary purpose of a classification is to enhance communication about the specific features of a condition by providing a descriptive framework for clinicians. Therefore, classification schemes should reflect the full spectrum of morphologic abnormalities within a given condition, and should be uncomplicated and easy for clinicians to remember and use. While an ideal classification would also guide treatment, provide insight into prognosis, and incorporate the etiologic mechanism of the condition, congenital classification systems often fall short of these goals.

The embryological development of the upper limb proceeds along three axes: proximal-distal, anterior-posterior (referred to postnatally as radial-ulnar by clinicians, because the fetal upper limb rotates during development), and dorsal-ventral1. The apical ectodermal ridge and the underlying mesoderm control proximal-distal development through a reciprocal loop of fibroblast growth factors and Wnt proteins2. The zone of polarizing activity located in the posterior (ulnar) limb mesoderm expands and posteriorizes the limb along the anterior-posterior (radial-ulnar) axis through a secreted morphogen, sonic hedgehog (SHH)3. The apical ectodermal ridge and the zone of polarizing activity are closely linked by a reciprocal feedback loop that maintains SHH expression at the posterior (ulnar)-distal border of the apical ectodermal ridge during progressive outgrowth. Dorsal ectoderm controls limb dorsalization through the secretion of Wnt7a and the induction of Lmx1b in the underlying dorsal mesoderm4. A reciprocal feedback loop between Wnt7a and SHH has also been demonstrated5. Thus, the integration of SHH into the pathways that control proximal-distal, anterior-posterior, and dorsal-ventral axes ensures coordinated patterning during each phase of limb outgrowth and development (i.e., humerus, forearm, and hand).