Cole–Carpenter syndrome

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Cole–Carpenter syndrome
Autosomal recessive - en.svg
Autosomal recessive pattern is the inheritance manner of this condition.
SpecialtyMedical genetics

Cole–Carpenter syndrome is an extremely rare autosomal recessive medical condition in humans. The condition affects less than 10 people worldwide. [1] It is characterised by dysmorphic features and a tendency to fractures.

Signs and symptoms

Facial dysmorphism- prominent eyes with a proptotic appearance, micrognathia

This condition is usually diagnosed in infancy.

Features of this condition include:[citation needed]


There are three forms of this syndrome.

Type 1 has mutations in the protein disulfide-isomerase (P4HB) gene located on the long arm of chromosome 17 (17q25).[2]

Type 2 have mutations in the protein transport protein Sec24D (SEC24D) gene located on the long arm of chromosome 4 (4q26).[3]

A third type has been described with a mutation in the cartilage associated protein (CRTAP) located on the short arm of chromosome 3 (3p22.3).[4]

Clinically these forms are very similar and are best differentiated by gene sequencing.

The third patient (first female) diagnosed with this condition, gene sequencing shows no abnormalities.


Protein disulfide-isomerase is involved in the hydroxylation of proline residues in preprocollagen. Protein transport protein Sec24D is a protein involved in vesicle transport. How mutations in the gene cause disease is not yet clear. Cartilage associated protein is involved in post translation modifications of collagen.[citation needed]


The diagnosis may be suspected on the basis of the constellation of clinical features. It is made by sequencing the P4HB, SEC24D and CRTAP genes.[citation needed]

Differential diagnosis


There is no specific treatment for this condition currently known and management of its various features is the norm.[citation needed]


This condition was first described in 1987.[1]


  1. 1.0 1.1 Cole DEC, Carpenter, TO (1987) Bone fragility, craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features: a newly recognized type of osteogenesis imperfecta. J Pediat 110: 76-80
  2. Rauch F, Fahiminiya S, Majewski J, Carrot-Zhang J, Boudko S, Glorieux F, Mort JS, Bächinger HP, Moffatt P (2015) Cole-Carpenter syndrome is caused by a heterozygous missense mutation in P4HB. Am J Hum Genet 96(3):425-431. doi: 10.1016/j.ajhg.2014.12.027
  3. Garbes L, Kim K, Rieß A, Hoyer-Kuhn H, Beleggia F, Bevot A, Kim MJ, Huh YH, Kweon HS, Savarirayan R, Amor D, Kakadia PM, Lindig T, Kagan KO, Becker J, Boyadjiev SA, Wollnik B, Semler O, Bohlander SK9, Kim J13, Netzer C (2015) Mutations in SEC24D, encoding a component of the COPII machinery, cause a syndromic form of osteogenesis imperfecta. Am J Hum Genet 96(3):432-439 doi: 10.1016/j.ajhg.2015.01.002. Epub 2015 Feb 12.
  4. Balasubramanian M, Pollitt RC, Chandler KE, Mughal MZ, Parker MJ, Dalton A, Arundel P, Offiah AC, Bishop NJ (2015) CRTAP mutation in a patient with Cole-Carpenter syndrome. Am J Med Genet A 167A(3):587-91. doi: 10.1002/ajmg.a.36916