The development of the upper limb begins during the fourth week of life in utero, when a limb bud, consisting of undifferentiated mesenchymal cells encased in ectoderm, develops. By 9 weeks, the bud has developed into an arm and hand with identifiable digits, and by 12 weeks the digits have differentiated.

Growth and differentiation are under the control of signal regions at the tip of the developing limb with complicated interactions and feedback systems (Figure 9.1). Induction of mesenchymal cells in the ‘progress zone’ at the tip of the developing limb occurs under the influence of specific zones. The apical epidermal ridge (AER) is the director of growth in the proximodistal axis (excision of the AER results in a limb stump only, while transplantation may result in a duplicate limb). Differentiation in the radioulnar axis is under the control of the zone of polarizing activity (ZPA) (transplantation of the ZPA can give rise to a ‘mirror hand’). Differentiation in the volardorsal axis is under the control of the dorsal ectoderm (excision and rotation of this zone causes dorsal muscles to form ventrally). Thus, there is a complicated interaction between genes and the proteins they encode, which induces the cells of the AER, ZPA and dorsal zone that drive limb developing and patterning. Anomalies in these processes result in anomalies in limb development, and may be the result of genetic mutation, interruption of a pathway at molecular level or gross insult. The aetiology of such insults can be environmental, e.g. radiation, infection or chemical (including drugs), or hereditary, as part of a syndrome.