Developmental abnormalities and hereditary conditions

Congenital bone diseases

Many diseases of the skeletal system are congenital in the sense that they become evident at or soon after birth. This does not imply that they all are genetically determined. Most are caused by factors operating during pregnancy, delivery, or early infancy.

Intrauterine injuries of the skeletal system were dramatically seen in children born of some women who received thalidomide, a drug previously used to treat morning sickness, during the initial three months of pregnancy. These children suffered severe extremity defects such as shortened or malformed limbs (phocomelia). Most intrauterine injuries are probably not caused by drugs, however, but perhaps by viral, hormonal, or mechanical factors. Intrauterine amputations, clubfoot, and congenital dislocation of the hip probably belong to this group. Birth injuries with fracture of the collarbone or humerus may occur because of mechanical difficulties during delivery; these fractures heal extremely fast.

Developmental abnormalities may affect isolated or multiple regions of the skeleton, or they may involve a specific tissue system; the latter are often hereditary. Examples of isolated abnormalities are partial or total absence of the collarbone, the radius (the long bone on the thumb side of the forearm), and the thighbone; congenital false joint in the shinbone (tibia); and absence of a middle segment of a limb (phocomelia). Treatment of these conditions is difficult, often requiring advanced transplantation or orthopedic devices and sometimes necessitating amputation in childhood. Multiple abnormalities occur in polyostotic fibrous dysplasia, in which affected bone is replaced by fibrous connective-tissue matrix. The condition may cause multiple deformities that require surgical correction.

Inherited disorders

Hereditary disorders of the skeleton include osteogenesis imperfecta, Hurler and Marfan syndromes, and several disorders of epiphyseal and metaphyseal growth centres. (For detailed treatment of these disorders, see connective tissue disease.)

Hereditary metaphyseal dysplasias, causing bone deformities near the joints, exist in several forms. The primary defect lies in the growth zone of the long bones. One of these conditions, hypophosphatasia, results from a deficiency of the enzyme alkaline phosphatase. Multiple defects in the growth zones of the skeleton are distinct from familial hypophosphatemia, a condition characterized by low phosphate levels in the blood; it affects the kidney primarily and the skeleton only secondarily. Hemophilia, finally, is a generalized hereditary condition that affects the skeletal system only secondarily by bleeding in the bones and joints.