Clinical and genetic landscape of Bruck syndrome in the Indian population

Abstract Background Bruck syndrome (BS) is a rare form of Osteogenesis imperfecta (OI) with congenital large joint contractures and bone fragility fractures. Evaluation of phenotypic and genotypic profiles of 14 children with FKBP10 and PLOD2 gene variants causing Bruck syndrome (BS) and highlighting the severe deformities in response to poor surgical treatment in the Indian cohort. Methods Patients with bone fragility were clinically evaluated. After informed consent, genotyping was done by next-generation sequencing, and the variants were validated by Sanger sequencing. These children were treated surgically and pamidronate was administered. Results Out of 14 children, 12 were with FKBP10 gene variants, and two with PLOD2 gene variants. The age at diagnosis varied from birth to four years. All were classified as type III by modified Sillence classification. twelve had joint contractures, mainly in the knees and elbows. Clubfeet was identified in seven, scoliosis in three, and severe kyphoscoliosis in three. Two had skull deformities, six with wormian bones, one with basilar invagination and another showing severe cervical compression myelopathy. Rib fractures in six, vertebral compression in nine, and protrusion acetabulae in three were noted. Surgical correction of the deformities by soft tissue release and bone shortening was partially successful, while growth modulation was unsuccessful as the implant failed. Nine of the patients were non-ambulant. Bone density was decreased in all, and the response to pamidronate was partial. This cohort had four novel FKBP10 variants and two PLOD2 variants. Conclusion The study highlights the proportionate representation of the two genes in our population, the severe deformities with poor response to surgical treatment, and novel variants in the population.