Cole-Carpenter syndrome type 1

(OMIM phenotype number #112240)

Cole-Carpenter syndrome is an extremely rare form of bone dysplasia. It was described for the first time in 1987, by Cole and Carpenter, as a new variant of OI (see also OI type I). In addition to severe bone fragility, the main features of the syndrome are craniosynostosis, communicating hydrocephalus, ocular proptosis, marked postnatal growth failure, and distinctive facial appearance.

Gene

P4HB gene, 17q25.3 (OMIM gene/locus number #176790). P4HB gene encodes protein disulfide isomerase (PDI).

Phenotype

Craniosynostosis, ocular proptosis, hydrocephalus, distinctive facial features, and bone phenotype similar to OI type IV with recurrent diaphyseal fractures.

Images

Fig. Radiographic Findings in Individual 2 at 18 years of age affected by Cole-Carpenter syndrome type 1. (A) Lateral skull radiograph showing severe midface hypoplasia. (B) The right upper extremity is severely deformed. (C) In the lower extremities, both femurs and tibias have undergone intramedullary rodding surgery. Epiphyses of both distal femurs are wide and seem filled with nodular structures (‘‘popcorn epiphyses’’). The right femur shows a large cystic area (asterisk) and no bone is visible in the mid- shaft area (arrow). (D) Wide epiphyses of the metacarpal and digital bones, thin cortices and a cystic appearance. Some of the end phalanges seem to be partially resorbed (arrows).

Reproduced from Am J Hum Genet, Vol 96, Rauch F, Fahiminiya S, Majewski J, et al. Cole-Carpenter syndrome is caused by a heterozygous missense mutation in P4HB, Pages 425-31, Copyright 2015, with permission from Elsevier.


References

  1. Rauch F, Fahiminiya S, Majewski J, et al. Cole-Carpenter syndrome is caused by a heterozygous missense mutation in P4HB. Am J Hum Genet. 2015 Mar 5;96(3):425-31.
  2. Amor DJ, Savarirayan R, Schneider AS, et al. New case of Cole-Carpenter syndrome. Am J Med Genet. 2000 Jun 5;92(4):273-7. Review.
  3. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  4. http://www.omim.org