lethal osteogenesis imperfecta

Osteogenesis Imperfecta, Type VII

Clinical Characteristics

Ocular Features:

Shallow orbits sometimes lead to severe and even progressive proptosis. Bluish sclerae are sometimes present.

Systemic Features:

Infants may be born with multiple fractures and adults are often short in stature. Hypoplasia of the midface, frontal bossing, sutural craniosynostosis, hydrocephalus, and shallow orbits are frequently present and contribute to what is sometimes considered a distinctive facial dysmorphism. Dentinogenesis imperfecta and hearing loss are variable features. Neurological development is normal.

Multiple fractures occur and may result in marked long bone deformities, scoliosis, and short stature. When the ribs are involved, respiratory insufficiency may result and can be responsible for early death. Type VII osteogenesis imperfecta is sometimes considered a lethal form of OI.

Genetics

Homozygous mutations in the CRTAP gene (3p22.3) are responsible for this condition. This gene codes for a cartilage-associated protein and in mice is highly expressed in chondrocytes at growth plates and around the chondroosseous junction.

This condition has been confused with Cole-Carpenter 1 syndrome (112240) but the latter is due to heterozygous mutations in P4HB (17q25.3) (PDI gene family).

Pedigree:

Autosomal recessive

Treatment

Treatment Options:

Fractures require stabilization and hydrocephalus, if present, needs to be treated promptly. Extreme proptosis can lead to inadequate hydration of the eye (especially the cornea) that may require lid surgery or orbital reconstruction.

References

Article Title:

Cole-Carpenter Syndrome Is Caused by a Heterozygous Missense Mutation in P4HB

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.

PubMed ID:

25683117

CRTAP mutation in a patient with Cole-Carpenter syndrome

Balasubramanian M, Pollitt RC, Chandler KE, Mughal MZ, Parker MJ, Dalton A, Arundel P, Offiah AC, Bishop NJ. CRTAP mutation in a patient with Cole-Carpenter syndrome. Am J Med Genet A. 2015 Jan 21. doi: 10.1002/ajmg.a.36916. [Epub ahead of print].

PubMed ID:

25604815

Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta

Barnes AM, Chang W, Morello R, Cabral WA, Weis M, Eyre DR, Leikin S, Makareeva E, Kuznetsova N, Uveges TE, Ashok A, Flor AW, Mulvihill JJ, Wilson PL, Sundara UT, Lee B, Marini JC. Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta. N Engl J Med. 2006 Dec 28;355(26):2757-64..

PubMed ID:

17192541

New case of Cole-Carpenter syndrome

Amor DJ, Savarirayan R, Schneider AS, Bankier A. New case of Cole-Carpenter syndrome. Am J Med Genet. 2000 Jun 5;92(4):273-7. Review.

PubMed ID:

10842295

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