Congenital limb deficiencies affect approximately 5 to 10 per 10,000 live births and affect the upper limb at a ratio of 2:1 relative to the lower limb.¹ For most congenital deficiencies, no exact causative factor can be identified. However, with an understanding of embryology, one can gain insight into the intrauterine timing of the causative insult. Most insults occur within the first trimester. Several known factors can influence early skeletal development. These include drugs (eg, thalidomide), toxins (eg, mercury), ionizing radiation, genetics, trauma, and poor intrauterine environments (eg, maternal diabetes). There are evolving data to suggest various modes of inheritance for different congenital deficiencies.^3,4,5

Maternal nutritional deficiencies such as folic acid deficiency have been linked to neural tube defects (such as myelomeningocele and spina bifida) but have not been definitively linked to congenital limb deficiency. All the same, nutritional supplements should be part of the antenatal diet because most major organ development occurs before the mother realizes she is pregnant. This highlights the importance of proper diet/nutrition for all women of childbearing age, particularly the ones planning on pregnancy. Later in pregnancy, mechanical and fetal development factors can lead to limb deficiency. A classic example is Streeter dysplasia (or intrauterine constriction band syndrome, amniotic band), which can lead to multimembral amputations with deep constriction bands on the limbs and tissue defects in the trunk and face.

Medical conditions can be associated with congenital limb deficiency and ought to be recognized early because further medical intervention can be lifesaving. In the autosomal recessive condition thrombocytopenia with absent radius syndrome, patients may have severe thrombocytopenia associated with the multimembral limb deficiency. A platelet count is mandatory, and treatment may be necessary to mitigate potential neurologic damage from intracranial hemorrhage. Platelet counts typically improve as the child ages. Likewise, in Fanconi pancytopenia syndrome, another autosomal recessive condition, patients can present with bleeding, pallor, recurrent infections, and reduction limb deformities (absence or deformity of a limb) or dislocated hips. Holt-Oram (hand-heart) syndrome, an autosomal dominant variable penetrance condition, is associated with upper limb reduction deformities and heart defects. Genetic counseling for these patients and their families is critical.

As in adults, acquired limb deficiencies in children can follow trauma, burns, infection, and neoplasm. In the Western world, lawnmower injuries, pedestrian-motor vehicle collisions, and thermal or electric burns remain the most common causes of acquired limb loss in children.^6,7 In areas of geopolitical conflict, injuries from ballistic and ordnance explosions remain an unfortunately common etiology of limb loss in children.⁸ In colder climates, frostbite remains a rare but potential cause of limb loss in children.

Neoplastic disease of the limbs, namely osteosarcoma and Ewing sarcoma, has largely been historically managed with amputation. As detection abilities improved, neoadjuvant therapies became more common, and limb-salvage options such as reconstructive implants became more durable, so limb salvage has become feasible. Amputation, however, remains an option when a functional and oncologically disease-free extremity cannot be achieved with salvage.⁹ For massive benign lesions such as in Klippel-Trenaunay syndrome, Proteus syndrome, or neurofibromatosis I, limb amputation may result in more functional or even lifesaving outcomes.

Septicemia associated with purpura fulminans remains a common infectious etiology of acquired limb deficiency in infants and children.¹⁰ Purpura fulminans is most commonly associated with meningococcemia. Although the incidence of meningococcus is declining secondary to vaccination efforts,¹¹ other bacterial strains such as pneumococcus and streptococcus may also result in limb gangrene and subsequent loss. Also, pressor-induced distal limb necrosis may develop in infants on pressors.