Enchondromatosis revisited: New classification with molecular basis

Abstract

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.

Insights into Enchondroma, Enchondromatosis and the risk of secondary Chondrosarcoma. Review of the literature with an emphasis on the clinical behaviour, radiology, malignant transformation and the follow up

“…Enchondromatosis encompasses several different subtypes of which Ollier disease (enchondromatosis) ( Figure 2) and Maffucci syndrome (enchondromatosis associated with soft tissue haemangiomas) ( Figure 3) are most common [7,8]. Other subtypes such as metachondromatosis, genochondromatosis, spondyloenchondrodysplasia, dysspondyloenchondromatosis and cheirospondyloenchondromatosis are rare [5,7].…”

“…Other subtypes such as metachondromatosis, genochondromatosis, spondyloenchondrodysplasia, dysspondyloenchondromatosis and cheirospondyloenchondromatosis are rare [5,7]. Most subtypes are non-hereditary, while some are autosomal dominant or recessive [5].…”

Dysspondyloenchondromatosis without COL2A1 mutation: Possible genetic heterogeneity

“…More recently, DSC was classified as type VII enchondromatosis by Superti-Furga et al [2012]. Among the subtypes of generalized enchondromatosis with spinal involvement, three distinct entities are described: (1) spondylenchondrodysplasia (SPENCD, OMIM 271550) characterized by intellectual disability, cerebral calcification, autoimmunity and mild to moderate vertebral involvement, which is due to mutations in ACP5 [Superti-Furga et al, 2012]; (2) metaphyseal enchondromatosis with 2-hydroxyglutaric aciduria (MC-HGA, OMIM 271550) characterized by intellectual deficiency, vertebro-metaphyseal involvement and hydroxyglutaric aciduria, which is due to mutations in IDH1 or IDH2 [Superti-Furga et al, 2012] and (3) DSC. Dysspondyloenchondromatosis is characterized by enchondromatosis and severe involvement of vertebrae leading to radiological aspects similar to those observed in vertebral segmentation anomaly.…”

Longitudinal Follow-Up of Two Patients with Dysspondyloenchondromatosis due to Novel Heterozygous Mutations in <b><i>COL2A1</i></b>

“…Glycine to glutamine substitution, as found in our patient 1, has not been reported in DSC patients before. Superti-Furga et al [2012] proposed a classification for enchondromatosis with molecular basis and classified DSC as a member of type 2 collagenopathies. They noted that the chondromatous changes in DSC are expected to be regressive rather than progressive.…”