Phenotypic spectrum and quality of life in pediatric Bruck syndrome due to FKBP10 and PLOD2 variants: a 2-center United Arab Emirates experience.

FKBP10

Biallelic FKBP10 or PLOD2 variants, an autosomal recessive form of osteogenesis imperfecta combining fragility fractures and joint contractures

Bruck syndrome is a rare autosomal recessive form of osteogenesis imperfecta caused by biallelic FKBP10 or PLOD2 variants, characterised by fragility fractures and congenital or progressive joint contractures. The authors describe 13 patients from 11 unrelated families followed in two tertiary paediatric centres in the United Arab Emirates, 12 with FKBP10 variants and one with PLOD2 variants, together with exploratory quality-of-life data from the Pediatric Quality of Life Inventory. The FKBP10 c.831dup variant was identified in 10 patients from eight unrelated families of Emirati, Sudanese and Indian background. Recurrent long-bone fractures occurred in 11 patients (85%), joint contractures in 6 (46%) and vertebral deformity in 9 (69%), with mobility ranging from independent ambulation to non-ambulatory status, including among carriers of the same c.831dup variant. The most impaired quality-of-life domain was physical functioning, at 47.2 ± 23.7, versus 72.7 ± 19.3 for emotional functioning.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Ten patients carrying the same c.831dup variant with mobility ranging from independent walking to complete non-ambulation is the clearest illustration that an identical genotype does not predict functional prognosis in this disease, and families deserve to hear it at result disclosure. The authors are rigorous enough to label their quality-of-life data exploratory, which they are with 13 patients of widely differing ages and a generic instrument. Recognising c.831dup as a recurrent variant across several national backgrounds rather than a local founder mutation has a direct practical consequence for relative screening strategy.

Analysis by Dr Thibaut Benquey