Endocrine Abstracts

JOINT2352

Introduction and Aim: Osteogenesis imperfecta (OI) is a hereditary disorder of connective tissue characterized by increased bone fragility, recurrent fractures, and skeletal deformities. Mutations in FKBP10 cause a rare and severe form of OI, known as OI type-XI. This study aims to investigate the clinical and phenotypic characteristics, as well as the skeletal deformities and cervical abnormalities, of patients with FKBP10 mutations.

Methods: A retrospective follow-up study of 17 children (10 male) with FKBP10 mutations (ten different biallelic variants) evaluated between 2000 and 2024 was undertaken.

Results: The patients were diagnosed at a mean age of 3. 2±4. 2 years (range: 0. 03-13. 5 years). Consanguinity was reported in 14 patients with a family history of OI in 11. Four had antenatal fractures, 9 had fractures within the first 3 months postnatally, and 4 experienced fractures within the first 3 years. The median follow-up duration was 4. 5±4. 7 years (range: 0-14. 5 years). Multiple fractures (more than 10) occurred in 70% (n = 12) of the patients. All patients had long bone fractures, with additional rib (82%, n = 14), sacrum-coccyx (64%, n = 11), clavicle (23%, n = 4), and pelvic fractures (17%, n = 3). Long bone deformities caused by recurrent fractures were detected in all patients. Bone deformities included pectus excavatum/carinatum (70%, n = 12), pes equinovarus (35%, n = 6), and genu varum (29%, n = 5). Vertebral issues included vertebral compression (64%, n = 11), spondylolisthesis (58%, n = 10), pars defect (23%, n = 4), fusion defect (23%, n = 4), ossified longitudinal ligament (n = 1), and platybasia (n = 1). Scoliosis was present in 88% (n = 15). Basilar invagination was observed in 47%. Hip deformities included coxa vara (41%, n = 7), pelvic rotation anomalies (41%, n = 7), and acetabular protrusion (23%, n = 4). Other findings included Wormian bones (58%, n = 10), JOINT contractures (58%, n = 10), blue sclera (29%, n = 5), dentinogenesis imperfecta (41%, n = 7), epidermolysis bullosa (23%, n = 4), cardiac problems in 3, hyperlaxity in 3, and no hearing loss. Additionally, 70% (n = 12) were immobile, and all patients had short stature. All patients received intravenous bisphosphonate treatment for 7. 2±4. 1 years (range: 0. 25-15 years). Corrective surgeries for long bone deformities were performed in ten patients. The median height SDS was −2. 3±3. 4 at the initial examination and −3. 6±2. 0 at the last examination.

Conclusion: FKBP10 mutations result in a variety of severe clinical manifestations, including fractures, deformities, and spinal abnormalities. The majority of patients experience multiple fractures early in life, highlighting the need for early intervention and continuous monitoring.

Keywords: FKBP10, osteogenesis imperfecta, deformities