Cole-Carpenter Syndrome 1

Clinical Characteristics
Ocular Features: 

The bony orbits are shallow and the eyes appear prominent as part of the facial and skull bone deformities.  The proptosis may be progressive and eventually interfere with blinking and normal surface wetting of the cornea. 

Systemic Features: 

This condition may superficially resemble osteogenesis imperfecta with osseous deformities and frequent fractures.  However, the occurrence of craniosynostosis and hydrocephalus helps to distinguish it.  Cranial sutures may be slow to fuse and macrocephaly has been described.  Communicating hydrocephalus can be a feature and may require shunting.  Some patients have osteopenia of the long bones that fracture easily.

The facial features are said to be distinctive with midface hypoplasia, low-set ears, micrognathia, and, of course, prominent globes.  Growth may be subnormal and a variety of limb bone and digital anomalies have been described.  Intelligence is normal, however.


This condition is the result of heterozygous mutations in the P4HB gene (17q25.3) (PDI family).

See Cole-Carpenter Syndrome 2 (616294) for a somewhat similar disorder that is recessively inherited.

Treatment Options: 

A frontal craniectomy may be necessary during early childhood to relieve the proptosis particularly when blinking is impaired.  Patients must be followed for the development of communicating hydrocephalus.  Long bone fractures require prompt treatment. 

Article Title: 


Rauch F, Fahiminiya S, Majewski J, Carrot-Zhang J, Boudko S, Glorieux F, Mort JS, Bachinger HP, Moffatt P. Cole-Carpenter Syndrome Is Caused by a Heterozygous Missense Mutation in P4HB. Am J Hum Genet. 2015 Mar 5;96(3):425-31.

PubMedID: 25683117

Cole DE, Carpenter TO. Bone fragility, craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features: a newly recognized type of osteogenesis imperfecta. J Pediatr. 1987 Jan;110(1):76-80.

PubMedID: 3794889