New intermediate phenotype between MED and DD caused by compound heterozygous mutations in the DTDST gene

Am J Med Genet A. 2010 Dec;152A(12):3036-42. doi: 10.1002/ajmg.a.33707.


DTDST mutations cause a spectrum of diastrophic dysplasia disorders characterized by defects of proteoglycans sulfation. Reduction of sulfate/chloride antiporter activity is manifested by lower sulfate uptake and depends on a combination of mutations in DTDST. We analyzed a family with an autosomal recessive form of bone dysplasia. Three affected brothers from this family are compound heterozygotes for C653S/A715V mutations. We classified their phenotype as a new intermediate form between diastrophic dysplasia and multiple epiphyseal dysplasia, manifested by shortening of stature, metatarsus adductus/club foot, mild brachydactyly, proximally placed thumbs and clinodactyly of the fifth fingers. Radiographs document platyspondyly most marked in the lower thoracic and upper lumbar spine, epiphyseal dysplasia affecting predominantly the femoral heads, widening of the metaphyses, narrow growth cartilage and multilayered patellae. Exaggerated lesser trochanters of femur, that is, "monkey wrench" sign, elevated greater trochanters, thin upper pubic rami, grossly normal carpal/tarsal bones and severe, early onset osteoarthritis were other notable features.

MeSH terms

  • Adult
  • Anion Transport Proteins / genetics*
  • Biological Transport / genetics
  • Bone Diseases, Developmental / diagnostic imaging
  • Bone Diseases, Developmental / genetics
  • Genes, Recessive
  • Heterozygote
  • Humans
  • Male
  • Mutation*
  • Nuclear Family
  • Osteochondrodysplasias / diagnostic imaging
  • Osteochondrodysplasias / genetics*
  • Phenotype*
  • Proteoglycans / genetics
  • Radiography
  • Sulfate Transporters
  • Sulfates / metabolism


  • Anion Transport Proteins
  • Proteoglycans
  • SLC26A2 protein, human
  • Sulfate Transporters
  • Sulfates