Osteogenesis imperfecta: a typical case

A 7-year-old boy with growth retardation (<2.5 SD, weight 24 lbs, <95th percentile, in accordance with growth) and motor development delay such as inability to walk, was referred to our hospital for management and counselling.

All bones are over-transparent suggesting osteopenia. Long bones are deformed due to muscle growth, which osteopenia cannot correct. Multiple fractures of different ages are seen. Metaphyses do not appear thickened, as they would be in rickets, and feature mild sclerosis due to previous perfusions of bisphosphonates.
Chest X-ray shows diffuse osteopenia and a series of old rib fractures on the right side.
In this case there is a known familial history of osteogenesis imperfecta, which narrows down the diagnosis.

Osteogenesis imperfecta features osteopenia and susceptibility to bone fractures with variable severity. [1] It is a group of heterogeneous connective tissue disorders. In most cases (>90%), it is caused by mutations in COL1A1 and COL1A2 genes (17q21.33 and 7q21.3) encoding the alpha1 and alpha2 chains of type 1 collagen, following an autosomal dominant transmission pattern. [2] As far as the COL1A1 and COL1A2 genes are concerned, genotype does not correlate well with its phenotype, thus making genetic counselling difficult.
Some rare autosomal recessive forms in other genes have been described: LEPRE1, CRTAP, and PPIB genes (1p34.1, 3p22 and 15q21-q22). These forms are always severe with marked hypotonia.


Several distinct clinical presentations of OI have been identified, based on the severity of symptoms and age of onset. The first classification has been established by Sillence in 1979, and has been completed since then: Type I is mild, type II is lethal, type III is severe, types IV, V, VI are moderate. Types VII and VIII are recessive. The other types refer to syndromic associations of OI. [3]
The main signs include short stature, multiple bone fractures, marked deformities, low density bones (ground glass aspect).
Blue sclera is a classical sign but has poor specificity.
However, the presence of Wormian skull bones is a quite specific sign for OI. [4] The acronym PORKCHOPS can be used to remember diseases associated with Wormian bones:
P - pyknodysostosis
O - osteogenesis imperfecta
R - rickets
K - kinky hair syndrome
C - cleidocranial dysostosis
H - hypothyroidism/hypophosphatasia
O - otopalatodigital syndrome
P - primary acroosteolysis (Hajdu-Cheney)/Pachydermoperiostosis/Progeria syndrome
S - syndrome of Down.
On the other hand, posterior rib fractures are a classical finding in child abuse. Although, in our case, the overall clinical history prevails.

Differential diagnoses include other causes of osteopenia, such as idiopathic juvenile osteoporosis, cole carpenter (OI + craniosynostosis + ocular proptosis) or Bruck syndrome (OI+ arthrogryposis), phosphatasia disorders, medication (steroids), nutritional deficiency, panostotic form of polyostotic fibrous dysplasia, and other causes of long bone deformations such as chondrodysplasia and non-accidental injury (multiple fractures without osteoporosis).

Antenatal diagnosis is possible thanks to US and molecular biology analysis.

Management should be multidisciplinary. Bisphosphonates are effective for pain management and quality of life improvement. [5] Vitamin D supplementation is essential throughout life. Surgery is involved in management of deformations [6], especially scoliosis and long bone bowing. Rehabilitation is useful to prevent falls.

Functional prognosis depends on the severity of the disease and on the quality of management. [7]