Double heterozygosity for pseudoachondroplasia and spondyloepiphyseal dysplasia congenita

Am J Med Genet. 2001 Nov 22;104(2):140-6. doi: 10.1002/ajmg.10062.


Pseudoachondroplasia (PSACH) and spondyloepiphyseal dysplasia congenita (SEDC) are autosomal dominant forms of short-limb short stature caused by mutations in genes that encode structural components of the cartilage extracellular matrix. PSACH results from mutations in the cartilage oligomeric matrix protein (COMP) gene, while SEDC is caused by mutations in the gene for type II procollagen (COL2A1). We report a child with a distinct skeletal dysplasia due to the combined phenotypes of PSACH and SEDC. The proband's mother had PSACH and his father had SEDC. The child was suspected of having both phenotypes on the basis of the severity of his clinical and radiographic findings, and this was confirmed by molecular analysis. The COMP gene mutation (C348R), while not previously published, is typical of those in PSACH patients, whereas the COL2A1 mutation (T1370M) is somewhat atypical, as it predicts an amino acid change within the carboxyl-terminal region of the protein. Both mutations segregated with their respective phenotypes within this family. The description and natural history of the double heterozygote phenotype may be useful in counseling families regarding risk and prognosis.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Achondroplasia / diagnostic imaging
  • Achondroplasia / genetics*
  • Cartilage Oligomeric Matrix Protein
  • Child, Preschool
  • Collagen Type II / genetics
  • DNA Mutational Analysis
  • Diseases in Twins
  • Extracellular Matrix Proteins / genetics
  • Genes, Dominant
  • Glycoproteins / genetics
  • Hand / diagnostic imaging
  • Heterozygote*
  • Humans
  • Male
  • Matrilin Proteins
  • Mutation
  • Mutation, Missense
  • Osteochondrodysplasias / diagnostic imaging
  • Osteochondrodysplasias / genetics*
  • Phenotype
  • Radiography


  • Cartilage Oligomeric Matrix Protein
  • Collagen Type II
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Matrilin Proteins
  • TSP5 protein, human