Dyggve-Melchior-Clausen disease (DMC)

Dyggve-Melchior-Clausen disease and Smith-McCort dysplasia

Dyggve-Melchior-Clausen disease (DMC; MIM 223800) and Smith-McCort dysplasia (SMC; MIM 607326) are severe and progressive autosomal recessive skeletal dysplasias caused by mutations in the dymeclin gene (DYM). Individuals with these disorders share many features including disproportionate short stature, a short barrel shaped chest with sternal protrusion, microcephaly, and epiphyseal and metaphyseal irregularities. Additional features include odontoid hypoplasia, scoliosis/kyphosis, platyspondyly with anterior beaking, and a double humped appearance of vertebral bodies.  Individuals with these disorders also have a lacy appearance of the iliac crest and abnormalities of the pelvis, hip and hands.  DMC is distinguished from SMC by the presence of severe psychomotor retardation. Both disorders are considered to result from loss of function mutations in the dymeclin gene. To date, nonsense, missense, splice site, frameshift and duplication mutations have been reported. A copy number variation detection methodology is required to detect the duplications.