Enchondromatosis revisited: New classification with molecular basis

• Published in: American journal of medical genetics. Part C, Seminars in medical genetics Vol. 160C; no. 3; pp. 154 - 164
• Main Authors: Superti-Furga, Andrea, Spranger, Jürgen, Nishimura, Gen
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.08.2012; Wiley Subscription Services, Inc
• Subjects: Bone matrix; bone tissue; enchondromatosis; Enchondromatosis - classification; Enchondromatosis - diagnostic imaging; Enchondromatosis - genetics; Enchondromatosis - pathology; Genetics; Humans; Radiography
• ISSN: 1552-4868; 1552-4876
• DOI: 10.1002/ajmg.c.31331

The so‐called “enchondromatoses” are skeletal disorders defined by the presence of ectopic cartilaginous tissue within bone tissue. The clinical and radiographic features of the different enchondromatoses are distinct, and grouping them does not reflect a common pathogenesis but simply a similar radiographic appearance and thus the need for a differential diagnosis. Recent advances in the understanding of their molecular and cellular bases confirm the heterogeneous nature of the different enchondromatoses. Some, like Ollier disease, Maffucci disease, metaphyseal chondromatosis with hydroxyglutaric aciduria, and metachondromatosis are produced by a dysregulation of chondrocyte proliferation, while others (such as spondyloenchondrodysplasia or dysspondyloenchondromatosis) are caused by defects in structure or metabolism of cartilage or bone matrix. In other forms (e.g., the dominantly inherited genochondromatoses), the basic defect remains to be determined. The classification, proposed by Spranger and associates in 1978 and tentatively revised twice, was based on the radiographic appearance, the anatomic sites involved, and the mode of inheritance. The new classification proposed here integrates the molecular genetic advances and delineates phenotypic families based on the molecular defects. Reference radiographs are provided to help in the diagnosis of the well‐defined forms. In spite of advances, many cases remain difficult to diagnose and classify, implying that more variants remain to be defined at both the clinical and molecular levels. © 2012 Wiley Periodicals, Inc.