Cole-Carpenter syndrome type 2

(OMIM phenotype number #616294)

Cole-Carpenter syndrome type 2 is caused by compound heterozygous mutation in the SEC24D gene. It is a rare autosomal recessively inherited skeletal disorder characterized by features of osteogenesis imperfecta (see also OI type I), such as pre- and postnatal bone fragility, and in addition skull ossification defects, craniofacial dysmorphism, and short stature (see also Cole-Carpenter syndrome type 1).

Gene

SEC24D gene, 4q26 (OMIM gene/locus number #607186). SEC24D is a component of the COPII complex involved in protein export from the endoplasmic reticulum (ER). The COPII complex is responsible for ER export of procollagen, among many other secretory proteins.

Phenotype

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

Images

Fig. Photographs and CT Scans of a patiente affected by Cole-Carpenter syndrome type 2. (A) At the age of 7 years. Note facial dysmorphism with down-slanting palpebral fissures, hypertelorism, dysplastic right ear, and pectus excavatus. (B) Lateral view. Note mid-face hypoplasia, micrognathia, frontal bossing, and dysplastic right ear. (C) Three-dimensional CT scan of the cranium at the age of 14 months. Note wide sagittal suture with a broad ossification defect frontoparietal apical. Sutura metopica is displaced to the bottom, as indicated by surrounding wormian bones. Coronal sutures, lambda sutures, and temporal sutures appear narrow and with premature ossification pattern without clear synos- tosis, but with multiple wormian bones enclosed. (D) Lateral view of a cranial CT scan taken at age 4 years and 4 months, with multiple wormian bones highlighted in different colors. Note an intraparietal suture on the left side (described as unilateral intraparietal suture). The large ossification defect fronto-parietal apical persisted. The sphenoid wings appear with an increased density and with multiple erosions.

Reproduced from Am J Hum Genet, Vol 96, Garbes L, Kim K, Riess A, et al. Mutations in SEC24D, encoding a component of the COPII machinery, cause a syndromic form of osteogenesis imperfecta, Pages 432-9, Copyright 2015, with permission from Elsevier.


References

  1. Garbes L, Kim K, Rieß A, et al. Mutations in SEC24D, encoding a component of the COPII machinery, cause a syndromic form of osteogenesis imperfecta. Am J Hum Genet. 2015 Mar 5;96(3):432-9.
  2. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  3. http://www.omim.org