Achondrogenesis: new nosology with evidence of genetic heterogeneity

Abstract

Achondrogenesis is a phenotypically diverse group of lethal osteochondrodysplasias characterized by severe micromelia, a short trunk, and a disproportionately large cranium. Cases of classic achondrogenesis Type I (Parenti-Fraccaro), and classic achondrogenesis Type II (Langer-Saldino) have been grouped on the basis of clinical, radiologic, and histopathologic features. Although further genetic heterogeneity has been proposed, broad acceptance has been lacking. Review of 79 cases, including examination of available radiographs of familial cases, permitted division into four radiographic prototypes. Cases were distinguished on the basis of specific skeletal features as well as a new parameter, the "femoral cylinder index" (CIfemur). Using these criteria, the affected siblings in 11 families were found to be concordant for prototype. Thus, identification of radiographic skeletal prototypes of achondrogenesis, and the observation of familial concordance for prototype, suggested the existence of at least four genetically distinct disorders, each having autosomal recessive transmission. These observations should provide further impetus for histopathologic and biochemical studies of the defects in achondrogenesis.