OMIM ID:
Osteogenesis Imperfecta, Type VII
Alternate Names
Defective Genes
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
Inheritance
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
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.