A new concept of skeletal dysplasias

The skeletal dysplasias form a large group of hereditary disorders characterized by abnormal growth and malformations of bone and cartilage. The clinical severity ranges from mildly affected short stature to lethal forms. Spranger classified approximately 200 different skeletal dysplasias in 1992, based on the clinical and radiographic features and the mode of genetic transmission. Etiopathogenesis of skeletal dysplasias is better documented now, with rapid accumulation of knowledge concerning defective genes and proteins causing this group of disorders. Mutations responsible for skeletal dysplasias may cause defects in the synthesis of structural proteins and in metabolic pathways, degradation of macromolecules, growth factors and receptors and transcription factors. Classifications by the International Working Group on Constitutional Diseases of Bone were based on the mutations in the same group gene taking into consideration the clinical and radiological findings (achondroplasia group, dysplasia with decreased bone density group and type II collagenopathies...). Clinical manifestations and radiological investigations are crucial for the differential diagnosis in skeletal dysplasias. However, prenatal diagnosis and postnatal definitive diagnosis are most often achieved by molecular analysis of the patient. Therefore, these groups of disorders require management by a multidisciplinary team of specialists, including pediatricians, genetic specialists, orthopedists and psychiatrists.