Decreased bone mineral density in Costello syndrome
| Autor: | Francesca Pantaleoni, Giovanna Mascolo, Giuseppe Zampino, Chiara Leoni, Silvia Persichilli, David A. Stevenson, Marco Tartaglia, P. Caradonna, Lucilla Martini, Sara De Santis, Roberto De Sanctis, Ilaria La Torraca |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism Biochemistry Proto-Oncogene Mas Bone remodeling Body Mass Index Young Adult Endocrinology Absorptiometry Photon Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA Costello syndrome Bone Density Internal medicine Genetics medicine Humans Femur Neurofibromatosis Child Molecular Biology Dual-energy X-ray absorptiometry Femoral neck Bone mineral 25-Hydroxyvitamin D 2 Lumbar Vertebrae medicine.diagnostic_test business.industry Femur Neck Costello Syndrome medicine.disease medicine.anatomical_structure costello sindrome Case-Control Studies Body Composition Noonan syndrome Female business bone mineral density Body mass index |
| Popis: | Costello syndrome (CS) is a multisystemic disorder characterized by postnatal reduced growth, facial dysmorphism, cardiac defects, cognitive impairment, skin and musculo-skeletal anomalies, and predisposition to certain cancers. CS is caused by activating germline mutations in the HRAS proto-oncogene. Similar to what is observed in other RASopathies, CS causative HRAS mutations promote enhanced signal flow through the RAF-MEK-ERK and PI3K-AKT signaling cascades. While decreased bone mineralization has been documented in other RASopathies, such as neurofibromatosis type 1 and Noonan syndrome, systematic studies investigating bone mineral density (BMD) are lacking in CS.Dual-energy X-ray absorptiometry (DXA) was utilized to assess BMD and body composition (fat and fat-free mass) in a cohort of subjects with molecularly confirmed diagnosis of CS (n = 9) and age-matched control individuals (n = 29). Using general linear regression, subtotal body (total body less head), lumbar, femoral neck and femur BMD parameters were compared considering age, sex, body mass index (BMI) and Tanner stage. Blood and urine biomarkers of bone metabolism were also assessed.All individuals with CS showed significantly lower mean values of subtotal, lumbar and femoral neck BMD compared to the control group (p ≤ 0.01). Similarly, mean total body mass and fat-free mass parameters were lower among the CS patients than in controls (p0.01). Low 25-OH vitamin D concentration was documented in all individuals with CS, with values below the reference range in two patients. No significant correlation between vitamin D levels and BMD parameters was observed.CS belongs to a family of developmental disorders, the RASopathies, that share skeletal defects as a common feature. The present data provide evidence that, similar to what is recently seen in NF1 and NS, bone homeostasis is impaired in CS. The significant decrease in BMD and low levels of vitamin D documented in the present cohort, along with the risk for pathologic fractures reported in adult individuals with CS, testifies the requirement for a preventive treatment to alleviate evolutive complications resulting from dysregulated bone metabolism. |
| Databáze: | OpenAIRE |
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