Smith-McCort dysplasia is a rare autosomal recessive osteochondrodysplasia characterized by short trunk dwarfism with a barrel-shaped chest, rhizomelic limb shortening, and specific radiologic features including marked platyspondyly with double-humped end-plates, kyphoscoliosis, metaphyseal irregularities, laterally displaced capital femoral epiphyses, ... Smith-McCort dysplasia is a rare autosomal recessive osteochondrodysplasia characterized by short trunk dwarfism with a barrel-shaped chest, rhizomelic limb shortening, and specific radiologic features including marked platyspondyly with double-humped end-plates, kyphoscoliosis, metaphyseal irregularities, laterally displaced capital femoral epiphyses, and small pelvis with a lace-like appearance of iliac crests. These clinical and radiologic features are also common to Dyggve-Melchior-Clausen syndrome (DMC; 223800), which is distinguished from SMC by the additional feature of mental retardation (summary by Dupuis et al., 2013). For a discussion of genetic heterogeneity of Smith-McCort dysplasia, see SMC1 (607326).
Alshammari et al. (2012) reported a consanguineous Saudi family in which 4 sibs and 2 first cousins had Dyggve-Melchior-Clausen syndrome and normal intelligence (Smith-McCort dysplasia). All were short and had variable degrees of progressive pectus carinatum deformity, limitation ... Alshammari et al. (2012) reported a consanguineous Saudi family in which 4 sibs and 2 first cousins had Dyggve-Melchior-Clausen syndrome and normal intelligence (Smith-McCort dysplasia). All were short and had variable degrees of progressive pectus carinatum deformity, limitation of joint mobility, and lumbar lordosis. The index patient had significant short stature and no gross craniofacial dysmorphism. He had a short neck, significant pectus carinatum, exaggerated lumbar lordosis, and limitation of elbow extension and interphalangeal joint flexion with difficulty making a fist. There was genu valgus and no evidence of organomegaly.
By exome sequencing of the proband in a consanguineous Saudi family segregating Smith-McCort syndrome linked to chromosome 4, Alshammari et al. (2012) identified a homozygous missense mutation in the RAB33B gene (K46Q; 605950.0001). Immunoblot analysis showed severe deficiency ... By exome sequencing of the proband in a consanguineous Saudi family segregating Smith-McCort syndrome linked to chromosome 4, Alshammari et al. (2012) identified a homozygous missense mutation in the RAB33B gene (K46Q; 605950.0001). Immunoblot analysis showed severe deficiency of RAB33B in patient cells compared with control cells, and patient fibroblasts also displayed a marked reduction in the immunofluorescence signal corresponding to RAB33B but comparable signal intensity to the Golgi marker giantin (602500). In a Turkish patient with Smith-McCort syndrome in whom Neumann et al. (2006) had found no mutation in the DYM gene (607461), Dupuis et al. (2013) identified a homozygous missense mutation in the RAB33B gene (N148K; 605950.0002). By Western blot analysis and immunofluorescence studies, Dupuis et al. (2013) found marked reduction of the RAB33B protein.