From Desbuquois Dysplasia to Multiple Epiphyseal Dysplasia: The Clinical Impact of a CANT1 Variant Across Five Unrelated Families.

Abstract

Multiple epiphyseal dysplasia (MED) is a heterogeneous group of chondrodysplasia characterized by arthralgia, early onset osteoarthropathy, and the radiographic findings of small, flat, and irregular-shaped epiphyses. Some patients with MED have mild short stature as well. MED is genetically heterogeneous caused by pathogenic variants in COMP, MATN3, COL9A1, COL9A2, COL9A3, and SLC26A2. In 2017, pathogenic variants in CANT1, which are responsible for Desbuquois dysplasia, have also been reported in the genetic etiology of MED. To date, only three patients have been reported with CANT1-related MED. Herein, we present clinical and radiographic findings of six additional patients from five unrelated families, all sharing the same c.375G > C; p.(Trp125Cys) variant in CANT1 gene. These patients exhibited the features of multiple epiphyseal dysplasia, along with some similarities to Desbuquois dysplasia, thereby broadening the clinical spectrum of CANT1-related disorders.