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CLASSIFICATIONS AND NOMENCLATURE

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Constitutional errors of bone development include dysostoses, disruptions, and skeletal dysplasias. The dysostoses are malformations of single bones, although multiple sites can be involved. These disorders usually are due to genetic defects that predominantly affect organogenesis. Disruptions are secondary malformations of bones, resulting from extrinsic interference with the normal developmental process by a toxic substance, infection, or transiently expressed gene (e.g., rubella embryopathy). The skeletal dysplasias (osteochondrodysplasias) are intrinsic developmental disorders of chondro-osseous tissue. There are over 400 recognized skeletal dysplasias. Unlike the dysostoses, the genetic defects of the dysplasias affect bone development in both fetal and postnatal life, and have little or no affect on organogenesis. The dysplasias consist of primary lesions in which a genetic mutation is expressed in chondro-osseous tissue (e.g., "classic" dysplasias such as achondroplasia) and secondary dysplasias that are caused by factors extrinsic to the skeletal system (e.g., metabolic disorders). There are also mixed disorders that have features of a dysostosis and a dysplasia, for example, cleidocranial dysostosis and nail-patella syndrome.1–8

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Patients with short stature can have truncal shortening, extremity shortening, or both. With some of the osteochondrodysplasias, extremity shortening is generalized or proportionate. In others, there is preferential shortening of segments of the extremities. Rhizomelia refers to disproportionate shortening of the humeri and femurs. Mesomelia is shortening of the forearms and lower legs. Acromelia refers to short hands and feet.

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Radiographic classification schemes of the osteochondrodysplasias are often based on features such as spinal involvement, the patterns of long bone involvement, joint deformities, and bone density. The epiphyseal dysplasias have small or irregular epiphyses as the predominant deformity. Metaphyseal dysplasias have widened, flared, and/or irregular metaphyses. A diaphyseal dysplasia has widening or other deformity of the diaphyses. Spondylodysplasias have vertebral deformities, often platyspondyly. The predominant features of some dysplasias are abnormally increased or decreased bone density. Classification based on genetic factors is also useful. However, there is considerable phenotypic variation between patients with similar mutations, similar phenotypes can occur with different genetic defects, and the defective genes are as yet unknown for some of these disorders.

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PREDOMINANT INVOLVEMENT OF METAPHYSES

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Achondroplasia

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Achondroplasia is the most common chondrodystrophic dysplasia, occurring in approximately 1 in 25,000 livebirths and accounting for approximately 80% of short-limb bone dysplasias. There are approximately 10,000 people in the United States with achondroplasia. Achondroplasia is transmitted as an autosomal dominant trait; approximately 80% of cases are due to spontaneous mutations. The responsible gene is fibroblast growth factor receptor 3 (FGFR3). The manifestations of achondroplasia are due to a subnormal rate of formation of qualitatively normal enchondral bone. This leads to shortening of the long bones and ribs and underdevelopment of the flat bones, facial bones, and base of the skull (i.e., the cartilaginous portion of the skull).9–12

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A number of clinical features are helpful for the diagnosis of ...

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