APA (Old Order Amish; Eastern Pennsylvania)

Inheritance: autosomal dominant
Genes: COL1A2

OI type 1
Brittle bone disease
Osteogenesis imperfecta tarda

Osteogenesis imperfecta
Brittle bone disease
Collagen disease
Blue sclerae

Osteogenesis Imperfecta Type I

Clinical Characteristics

General description (for patients):

Osteogenesis imperfecta (OI) is the most common disease causing recurrent fractures in children.  It can also be responsible for fractures in adults as well. OI is a condition resulting from abnormalities of the genes that control the production of a protein called collagen which is the main protein in bone and essential for its strength.  Due to a lack of normal collagen in the bones, they break easily, often from mild trauma or with no apparent cause.  Multiple fractures are common, and in severe cases, can occur even before birth.  Multiple types can be distinguished by their signs and symptoms, although their characteristic features overlap.  Some individuals also develop deafness as adults, and teeth may develop abnormally.   

Medical description:  

Type I osteogenesis imperfecta is less severe than other types and most often associated with blue sclerae.  The milder forms of OI, including type I, are characterized by bone fractures during childhood and adolescence that often results from minor trauma.  There is a wide range in severity which is not always correlated with the type of OI.  In Type I, fractures are uncommon during the neonatal period. They usually heal readily and without deformity with good orthopedic care.  Self-reported fractures in a large Amish pedigree were 3.65 times as frequent as in their unaffected relatives.  Affected individuals are usually of normal or near normal height unless they have more severe disease in which case kyphoscoliosis may develop.   Half of reported families have a conductive or mixed type of hearing loss, usually beginning in late adolescence.  Dentinogenesis may be abnormal although infrequent in Type I.  In most people, the diagnosis can be made from the history and pattern of fractures and the presence of the associated clinical findings.  In severely affected people, X-rays may show evidence of previous fractures.  Some women with severe postmenopausal osteoporosis have been found to have type I OI.


OI is usually inherited in an autosomal dominant manner.  Mutations in the COL1A1, COL1A2, CRTAP, and LEPRE1 genes cause various types of osteogenesis imperfecta.  A large pedigree with a mutation (2098G>T) in COL1A2 has been reported in the Amish of Pennsylvania.  A total of 48 individuals with this mutation could be traced to a single ancestral couple.


There is no cure or drug treatment for OI.  Treatments are aimed at increasing overall bone strength to prevent fracture and maintain mobility.  The basis of treatment is competent orthopaedic care at the time of fractures, to ensure that each fracture heals in a good position.  Patients should be mobilised as early as possible to minimise the loss of bone due to immobilisation.  “Rodding” operations, in which fixed or telescopic metal rods are inserted into the shafts of bones, can be helpful in children with frequent fractures or appreciable deformity.  Trials of various bisphosphonate drugs are in progress and have given encouraging results in some patients with the more severe types of OI.


Most people with OI have a normal life expectancy and lead very productive lives.  They can attend regular schools, enjoy a wide range of career and lifestyle choices, experience fulfilling relationships, and have children.

Ancillary treatments and support: 

Avoidance of trauma.

Specialists and speciality centers:

Orthopedists, nutritionists.


Cheung, M.S.,  and Glorieux, F.H.:  Osteogenesis Imperfecta:  update on presentation and management.  Rev.  Endocr. Metab. Disord.  9: 153-60, 2008.  PubMed ID: 18404382

Martin, E., and Shapiro, J.R.:  Osteogenesis imperfecta: epidemiology and pathophysiology. Curr. Osteoporos Rep. 5: 91-7, 2007.  PubMed ID: 17925189

McBride, D., Streeten, E.A., Mitchell, B.D., and Shuldiner, A.R.:  Variable expressivity of a COL 1A2 gly-610-cys mutation in a large Amish pedigree.  Am. J. Hum.  Genet. 71: (Abstract #1047), 351, 2002.


Osteogenesis Imperfecta Foundation

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