The development of the limbs and motor systems is a complex and orchestrated process, the interruption or disturbance of which can result in limb deficiency or deformity and subsequent disability. Following birth, the developmental processes of the growing child are integral to motor capabilities and should be considered when fitting prosthetic devices. This chapter will review the childhood stages of motor development.

Limb development occurs via multiple signaling pathways, each responsible for its own differentiation, yet working in concert with complex interactions, including signaling, regulation, feedback loops, and maintaining the additional axes of development.^1,2 The limbs start to appear at the end of the fourth week and continue to develop through the eighth week after fertilization.

The most critical period of limb development is 24 to 36 days after fertilization (during weeks 4 to 6), when the embryo undergoes rapid tissue proliferation.³ Often, the mother is not aware of her pregnancy; therefore, exposure to teratogenic agents is difficult to prevent. Inhibition of limb bud development in the fourth week can result in complete absence of the limb, whereas interruption of the growth or development in the fifth week can result in partial absence.

Teratogenic factors affecting limb development include drug use during pregnancy, infections, chorionic villus sampling, or exposure to toxins.⁴ Some medications affect limb development, including thalidomide, retinoic acid, and misoprostol. The most famous of these is thalidomide, which was marketed in the 1950s to mothers for management of nausea and vomiting during pregnancy. Thalidomide was available in most European countries and Canada, and it could be obtained without a prescription in Germany. In 1961, Widukind Lenz, a German pediatric geneticist, began investigating an increasing number of children born with severe limb anomalies; his findings resulted in a withdrawal of thalidomide from the market.⁵ Thousands of exposed children exhibited phocomelic limb anomalies, facial malformations, and often, internal organ involvement.

Teratogenic causes are often difficult to study, particularly because prenatal history can be complicated by maternal recall bias.⁶ Limb deficiencies also can be caused by vascular disruption (eg, amniotic band syndrome, in which fibrous bands constrict the vascular supply to the limbs), vascular malformations (such as Poland syndrome [subclavian artery disruption sequence]), or genetic factors (often a spontaneous point mutation in an otherwise normal family). Of the more than 120 clinically defined congenital limb deficiencies, less than 40% have a known molecular origin.⁷ Many limb deficiencies are likely the result of an interaction of genetic and environmental factors (multifactorial inheritance). No racial predilection has been observed. In addition to disruptions in the uterine environment as noted previously, risk factors for congenital limb deficiency include maternal cigarette smoking (longitudinal deficiencies),⁸ poorly controlled maternal diabetes (association with longitudinal deficiencies and sacral agenesis with hypoplastic lower extremities),⁹ and maternal thrombophilia.¹⁰

Amniotic band syndrome (also known by more than 30 other names, including congenital constriction band syndrome, amniotic constriction band, and amnion rupture sequence) is a very heterogenous group of clinical anomalies, which can include congenital limb deformities, cleft lip and palate, constriction rings, and talipes equinovarus. There is no unanimously accepted etiology for this constellation of findings.² Animal studies have suggested that the
incidents leading to limb deficiency in amniotic band syndrome may be caused by a cascade of hypoxia, cell damage, hemorrhage, tissue loss, and reperfusion.⁴

In childhood, development occurs in discontinuous bursts, with complex skills building on simpler skills. A proper understanding of developmental motor milestones (Table 1) is important when considering prosthetic prescription in the child with a limb deficiency. Prosthetic fitting should reflect the child’s functional needs, not the rather arbitrary chronologic age.⁵ Most children with a limb deficiency experience normal development. Those with bilateral upper limb deficiencies can experience a delay in reaching some milestones or miss them completely because of mechanical problems. Parents should be encouraged to treat a child with a limb deficiency in the same manner as they would treat any child, allowing them to explore their environment and develop new skills by experimentation.