Phenotypic Spectrum and Quality of Life in Pediatric Bruck Syndrome Due to FKBP10 and PLOD2 Variants: A Two-Center United Arab Emirates Experience

Abstract

Abstract Bruck syndrome is a rare autosomal recessive form of osteogenesis imperfecta (OI) caused by biallelic variants in FKBP10 or PLOD2, and characterized by fragility fractures with congenital or progressive joint contractures. We describe 13 patients from two tertiary pediatric centers in the United Arab Emirates and report exploratory health-related quality-of-life data using the Pediatric Quality of Life Inventory (PedsQL). Published molecularly confirmed cases were reviewed solely to contextualize the cohort. The cohort comprised 13 patients (7 female and 6 male; median age, 4 years; range, 13 months-14 years) from 11 unrelated families, including two sibling pairs. Twelve patients had FKBP10 variants and one had PLOD2 variants. FKBP10 c.831dup was identified in 10 patients from eight unrelated families of Emirati, Sudanese, and Indian backgrounds. Recurrent long-bone fractures occurred in 11 patients (85%), joint contractures in 6 (46%), and vertebral deformity in 9 (69%). Mobility ranged from independent ambulation to nonambulatory status, including among patients carrying c.831dup. PedsQL domain scores (mean ± SD) were 47.2 ± 23.7 for physical functioning, 72.7 ± 19.3 for emotional functioning, 57.7 ± 22.5 for social functioning, and 64.5 ± 25.0 for school functioning. Physical functioning had the lowest mean domain score; these findings are descriptive because of the small, age-heterogeneous cohort and the limitations of a single generic instrument. This two-center case series expands the reported phenotypic and functional spectrum of FKBP10- and PLOD2-related disease. The FKBP10 c.831dup variant was identified across three national backgrounds in the UAE cohort and has been reported in other populations, supporting its interpretation as a recurrent variant brought into homozygosity by regional consanguinity rather than a UAE-specific founder mutation. The variability in skeletal severity, mobility and functional outcome, including among patients sharing the same variant, highlights the need for individualised multidisciplinary care addressing fracture prevention, mobility, spinal surveillance, rehabilitation and long-term function.