Bone Abstracts

Cole-Carpenter syndrome (OMIM 112240) is characterised by bone fragility, craniosynostosis, ocular proptosis, hydrocephalus and a distinctive facial appearance. Intelligence is reported to be normal. In 1986, Cole and Carpenter reported two unrelated infants with multiple fractures and deformities of bone, with a skeletal phenotype similar to severe osteogenesis imperfecta (OI). In addition, these patients also had proptosis, blue sclerae, hydrocephalus and a distinct facial gestalt. They were reported to be of normal intelligence. Radiologically, these patients had characteristic skeletal manifestations including craniosynostosis and deformities similar to severe progressive OI. Since the first description, there have only been a few other case reports of patients with a similar phenotype. Collagen studies performed in previously reported patients have been normal. The molecular basis of this syndrome has not been elucidated and the inheritance pattern is still unknown.

We report a 12-year old patient with Cole-Carpenter syndrome who has a homozygous c.118G>T mutation in exon 1 of the CRTAP gene. We describe the clinical features and correlate this with her molecular results. This is the first report towards elucidating the molecular basis of Cole-Carpenter syndrome. Mutations in CRTAP have been described in association with type 2 (perinatally lethal) and type 3 OI (severely-deforming bones with extreme short stature, scoliosis and dentinogenesis imperfecta). The majority of CRTAP mutations result in a functional null allele with a consequent absence or significant reduction in levels of the protein. The spectrum of phenotypes associated with CRTAP deficiency range from severely-deforming to lethal presentations.

This report provides an aetiological basis for Cole-Carpenter syndrome, with an autosomal recessive inheritance and also expands the phenotypic spectrum for patients with mutations in the CRTAP gene. It also raises the possibility that Cole-Carpenter syndrome is a variant of type 3 OI and was never a distinct, rare bone fragility syndrome and postulate that craniosynostosis may be an acquired phenomenon in type 3 OI, further strengthening this suggestion.

Disclosure: The authors declared no competing interests.