Achondrogenesis

Abstract

There are more than 200 known skeletal dysplasias, 50 of which are recognizable at birth and constitute the fetal skeletal anomalies. Approximately 40% of fetal skeletal anomalies result in a stillbirth or cause neonatal death.17 Although fetal skeletal anomalies are relatively infrequent, with an overall incidence of 2.4 per 10,000 births, a disproportionately high incidence (1 in 110) of these disorders can be found as the cause of perinatal death. The most common lethal congenital anomaly is thanatophoric dysplasia, with incidence of 1 in 16,700. Achondrogenesis is also a lethal skeletal anomaly and occurs at approximately one third the frequency (1 in 43,400). Together these disorders account for the majority (62%) of perinatal death associated with skeletal anomalies. The most common nonlethal disorder is achondroplasia, with an incidence of 1 in 27,100.4The skeletal dysplasias represent a heterogeneous group of disorders with a wide variety of frequency, mode of transmission, clinical presentation, and prognosis. The International Nomenclature of Constitutional Diseases of Bone was revised in 1984 and classifies the skeletal dysplasias into five general categories. First are the osteochondrodysplasias. These disorders are abnormalities of the growth and development of the bone, cartilage, or both. This group includes the majority of fetal skeletal anomalies including most lethal forms of skeletal dysplasia. The second group includes the dysostoses, which include single or combination malformations of individual bones. This group is further subdivided into the areas of predominate involvement, such as cranial, facial, axial, or extremity. The third group includes disorders of idiopathic osteolysis that affect the resorption of bone. This group can be subdivided into the phalangeal, tarsocarpal, and multicentric types. The fourth group includes the skeletal disorders associated with chromosomal aberrations. The fifth group is made up of primary metabolic disorders that have bony manifestations.7 Care should be taken to classify these disorders correctly to determine an accurate prognosis and recurrence rate. International skeletal dysplasia registries have been established to assist in correct classification and to accumulate accurate data to define further this complex group of disorders.11 A detailed review of all the numerous skeletal dysplasias is beyond the scope of this article. Instead, the more common skeletal anomalies are identified with emphasis on those that can be diagnosed prenatally, shortly after birth or result in perinatal death.