Smith-Mccort Dysplasia 1

A number sign (#) is used with this entry because Smith-McCort dysplasia-1 (SMC1) is caused by homozygous or compound heterozygous mutation in the DYM gene (607461) on chromosome 18q21.

Mutations in the same gene cause Dyggve-Melchior-Clausen disease (DMC; 223800), which is radiologically identical but has the additional feature of mental retardation.

Description

Smith-McCort dysplasia is a rare autosomal recessive osteochondrodysplasia characterized by short limbs and trunk with barrel-shaped chest. The radiographic phenotype includes platyspondyly, generalized abnormalities of the epiphyses and metaphyses, and a distinctive lacy appearance of the iliac crest, features identical to those of Dyggve-Melchior-Clausen disease. Spinal cord compression due to atlantoaxial instability occurs in both SMC and DMC (Spranger et al., 1976; Nakamura et al., 1997).

Genetic Heterogeneity of Smith-McCort Dysplasia

Smith-McCort dysplasia-2 (SMC2; 615222) is caused by mutation in the RAB33B gene (605950) on chromosome 4q31.

Clinical Features

Nakamura et al. (1997) examined iliac crest biopsies from 2 patients with Smith-McCort dysplasia. The lace-like appearance of the iliac crests, which is a characteristic radiologic sign, was caused by bone tissue deposited in a wavy pattern at the osteochondral junction. The growth plate showed abnormal enchondral ossification with no columnarization of chondrocytes. Electron microscopy demonstrated chondrocytes with dilated cisternae of rough endoplasmic reticulum (RER) containing fine granular or amorphous material similar to what had been reported in cases of DMC syndrome. Thus, Nakamura et al. (1997) concluded that Smith-McCort dysplasia has pathologic changes in common with DMC disease as an RER storage disorder, even though the mental condition is different.

Mapping

In a consanguineous family from Guam affected by Smith-McCort dysplasia, Ehtesham et al. (2002) performed a genomewide scan and found evidence of linkage to loci on chromosome 18q12. Analysis of a second, smaller family was also consistent with linkage to this region, producing a maximum combined 2-point lod score of 3.04 at a recombination fraction of zero for marker D18S450. A 10.7-cM region containing the disease locus was defined by recombination events in 2 affected individuals in the larger family. Furthermore, all affected children in the larger family were homozygous for a subset of marker loci within this region, defining a 1.5-cM interval likely to contain the mutated gene. Analysis of 3 small, unrelated families with DMC syndrome provided evidence of linkage to the same region, a result consistent with the hypothesis that the 2 disorders are allelic.

Molecular Genetics

In patients with SMC, Cohn et al. (2003) identified mutations in the DYM gene (607461.0005-607461.0006).

In an affected 6-year-old girl, offspring of consanguineous parents from the Portuguese Madeira Island, Santos et al. (2009) identified homozygosity for a mutation in the DYM gene (607461.0010).

Nomenclature

Spranger et al. (1976) suggested the designation Smith-McCort dwarfism for this disorder.