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osteogenesis imperfecta; osteopsathyrosis; fragilitas ossium; Lobstein's disease (OI)
Inherited disorder characterized by osteopenia & brittle bones.
Classification:
1) type 1, mildest form, autosomal dominant
2) type 2, lethal in utero or shortly after birth
3) type 3, tends to become more severe with age
4) type 4, bone fragility variable, autosomal dominant
Epidemiology:
- most prevalent heritable disorder of connective tissue [6]
Pathology:
1) generalized osteopenia
2) aortic incompetence
Genetics:
- most patients have defects in 1 of the 2 alleles for type-1 collagen alpha chain (COLA1, COLA2) [1]
- contiguous gene deletion involving COL1A1 or COLA2 may complicate phenotypic expression [6]
Clinical manifestations:
1) musculoskeletal manifestations
a) bone fractures with little pain
b) skeletal defomities: skull, trunk, limbs
c) short stature
d) hypermobility of joints
2) teeth may be normal, discolored or grossly abnormal (dentinogenesis imperfecta)
3) ocular manifestations
a) exophthalmos
b) blue sclerae (characteristic but not specific)
4) hearing loss
a) generally begins in 2nd decade of life
b) 90% of patients over age 30
c) conductive, sensorineural or mixed
d) middle ear bony & cartilagenous deformities
5) progressive neurological symptoms may result from basilar compression & communicating hydrocephalus
* cognitive impairment, delay in speech development, & self-mutilation are not typically associated [6]
Radiology:
1) hypoplastic bone
2) fracture deformities
Management:
1) treatment is ineffective
2) severely affected children should be provided with
- physical therapy,
- surgical management of fractures & skeletal deformities
- vocational education
3) surgical replacement of stapes for hearing loss
4) aggressive treatment pneumonia & cor pulmonale
5) growth hormone may increase growth in children
6) bisphosphorates have been used to prevent bone loss
- no controlled studies
7) audiology & dental evaluations
8) patient education
a) an appropriate amount of exercise may prevent bone loss due to inactivity
b) counseling & emotional support
- preterm genetic counseling
c) prenatal diagnosis
1] prenatal ultrasonography will detect severely affected fetuses at 16 weeks
2] synthesis of abnormal pro-alpha collagen chains on chorionic villa biopsies at 8-12 weeks of gestation
9) prognosis
a) many patients live productive lives despite severe deformities
b) risk of fractures decreases after puberty
c) risk of fractures in women increases during pregnancy & after menopause
Specific
Bruck syndrome; osteogenesis imperfecta with congenital joint contractures
gnathodiaphyseal dysplasia; osteogenesis imperfecta with unusual skeletal lesions; gnathodiaphyseal sclerosis
osteogenesis imperfecta type I; osteogenesis imperfecta tarda
osteogenesis imperfecta type II; osteogenesis imperfecta congenita, neonatal lethal form
osteogenesis imperfecta type III
osteogenesis imperfecta type IV with normal sclera
osteogenesis imperfecta type X (type 10)
General
connective tissue disease; soft tissue disease
developmental bone disorder
genetic disease of bone/skeletal system
References
- DeGowin & DeGowin's Diagnostic Examination, 6th edition,
RL DeGowin (ed), McGraw Hill, NY 1994, pg 918
- Harrison's Principles of Internal Medicine, 14th ed.
Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 2187-89
- Harrison's Principles of Internal Medicine, 13th ed.
Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994,
pg 1038, 2111-12
- Medical Knowledge Self Assessment Program (MKSAP) 16, 18.
American College of Physicians, Philadelphia 2012, 2018,
- Glorieux FH.
Osteogenesis imperfecta.
Best Pract Res Clin Rheumatol. 2008 Mar;22(1):85-100
PMID: 18328983
- Mannstadt M et al
Case records of the Massachusetts General Hospital.
Case 24-2014 - A 27-Year-Old Man with Severe Osteoporosis and
Multiple Bone Fractures.
N Engl J Med 2014; 371:465-472July 31, 2014
PMID: 25075839
http://www.nejm.org/doi/full/10.1056/NEJMcpc1404139
- National Institute of Arthritis and Muscluloskeletal and Skin Diseases (NIAMS)
Osteogenesis Imperfecta
https://www.niams.nih.gov/health-topics/osteogenesis-imperfecta