Discoidin domain receptor 2 (DDR2) is a tyrosine kinase receptor expressed in mesenchymal cells. In the past decade, DDR2 has been shown to be involved in many processes of human disease including liver fibrosis, breast cancer, osteoarthritis and rheumatoid arthritis. Specifically, biallelic mutations in DDR2 were shown to cause spondylo-epiphyseal-metaphyseal dysplasia (SMED) with short limbs (SMED-SL), a rare form of autosomal recessive skeletal dysplasia. Skeletal involvement can include disproportionate short stature, a narrow chest, brachydactyly, platyspondyly and distinct facial features. An important diagnostic clue is often abnormal stippled calcifications in cartilage, highly suggestive of the disorder.
We summarize herein clinical and molecular data of a cohort of ten probands with SMED-SL, including three new pathogenic mutations discovered in DDR2. Of note, several patients presented additionally with extra-skeletal manifestations, including mitral valve prolapse and lung hypoplasia. These data add to the current knowledge regarding the phenotypic features and molecular basis of this rare skeletal dysplasia.
As DDR2 has been implicated in the pathogenesis of both common and rare disorders, we suggest that studying rare disorders may open a window towards better understanding of more prevalent ones.
