Bruck syndrome in 13 new patients: Identification of five novel FKBP10 and PLOD2 variants and further expansion of the phenotypic spectrum.

ABSTRACT

Bruck Syndrome (BS) is a very rare disorder characterized by osteogenesis imperfecta (OI) associated with congenital contractures and is caused by mutations in FKBP10 or PLOD2 genes. Herein, we describe 13 patients from 9 unrelated Egyptian families with BS. All patients had white sclerae, recurrent fractures, kyphoscoliosis and osteoporosis with variable degrees of severity. Large joint contractures were seen in 11 patients, one patient had contractures of small interphalangeal joints, and one patient had no contractures. Unusual findings noted in individual patients included microcephaly, dental malocclusion, enamel hypoplasia, unilateral congenital dislocation of knee joint, prominent tailbone, and myopathy. Nine different variants were identified in FKBP10 and PLOD2 including five novel ones. FKBP10 variants were found in six families (67%) while PLOD2 variants were identified in three families (33%). The four families, with two affected sibs each, showed inter- and intrafamilial phenotypic variability. In conclusion, we report five novel variants in FKBP10 and PLOD2 thus, expanding the mutational spectrum of BS. In addition, our results expand the phenotypic spectrum, describe newly associated orodental findings, and further illustrate the phenotypic overlap between OI and Bruck syndrome supporting the suggestion of considering BS as a variant of OI rather than a separate entity.