Osteogenesis imperfecta: klinische en genetische heterogeniteit

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• Osteogenesis imperfecta is a hereditary connective tissue disorder characterized primarily by fractures with no or small causal antecedent; in most patients this is a consequence of diminished or abnormal production of collagen type I.

• It is a clinically heterogeneous disorder: it has been proposed recently to classify osteogenesis imperfecta in types I-V on the basis of the clinical picture and radiology.

• It is also a genetically heterogeneous disorder; 90% of cases are due to autosomal dominant mutations, while the remaining 10% are due to autosomal recessive mutations or of unknown cause.

• Osteogenesis imperfecta type I and to a lesser extent type IV are important differential diagnostic considerations in case of suspicion of non-accidental injury (NAI).

• When osteogenesis imperfecta is suspected, DNA analysis of the dominant COL1A1 and COL1A2 genes is currently the starting point for laboratory diagnosis unless there are strong indications for a recessive cause.

• Protein analysis based on skin biopsy remains indicated in specific cases.