Progress in gene discovery has identified at least 23 genes including the 2 COLI genes, in which mutations result in at least one Osteogenesis Imperfecta phenotype. The International Bone Dysplasia Nosology Committee grouped the syndromes arising from mutations in these genes into five OI phenotypes. Autosomal Dominant, Recessive, and X-linked inheritance has been confirmed.

At Westmead a multidisciplinary OI diagnostic and management service for children was commenced in 1986 and for young adults in transition in 2016. We have consulted for >350 patients and >200 of these have received a bisphosphonate treatment regimen. The development of Massively Parallel Sequencing (MPS) using a targeted exome panel has facilitated patient care by providing additional genomic diagnosis. It is now clear that some therapies such as bisphosphonates have only attenuated effects or effects of short duration in specific disorders such as OI type 3-FKBP10 type, OI type 3/4-SERPINF1 and Spondylo-ocular syndrome. In adults, Teriparatide is ineffective in OI type 3/4 and Denosumab poses real risks for Osteonecrosis of the Jaw. Accordingly emphasis has been placed on genomic as well as phenomic typing to guide pharmacologic interventions. Although > 85% of patients studied to date have defined mutations in COL1 genes, Westmead’s OI service has also cared for multiple patients with rare OI disorders. These include patients with mutations in IFITM5 (N=5), FKBP10 (N=3), CRTAP (N=2), Spondylo-ocular (XYLT2)(N=2), and PLOD2 (N=1). Mutation analysis by MPS has been highly valuable in deciding on treatment for phenotypically characterized patients. Services need to position themselves for several new therapeutic approaches including treatment trials of fresolimumab for OI with dysregulated TGF beta signalling and therapies which counteract the Unfolded Protein Response in certain types of OI.