Background: Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue. Cardinal features affect cardiovascular system, eyes and skeleton. It is caused by mutations of FBN1 gene, which encodes the extracellular matrix protein fibrillin 1. The improper activation of TGFβ, due to defective fibrillin-1, is the pathophysiological mechanism. The altered modulation leads to overgrowth of long bones (disproportionate stature) and altered bone morphology.
Objective: Aim of our study was to investigate bone mineral density and risk of fracture in children with MFS.
Method: Seventy-three patients (35 girls and 38 boys) were enrolled in the study from 2009 to 2013: all had a clinical diagnosis of MFS by revisited Ghent Criteria (2010). The mean age at examination was 10.2 (4.0) years in girls, and 9.8 (3.6) years in boys. The mean weight Z-scores was −0.01 (ranging from −3.2 to 3.5) and the mean height Z-score was 1.9 (−1.86.3). We measured bone mineral density (BMD) by dual-energy X-ray absorptiometry at the lumbar spine. Because MFS patients are taller than healthy peers, BMD measurements were corrected for height Z-scores, and expressed as BMD Z-score/height.
Results: Mean BMD Z-score/height at lumbar spine was −1.9 (−6.7 to 1.0), significantly lower than average (P<0.0001): in girls −1.8 (−4.2 to −0.27), in boys −2.1 (−6.7 to 1.06), P<0.0001 in both. Nineteen patients (13 males and six females) reported to have had one or more fractures: 17 patients had one fractures, one (boy) had two fractures, and one (boy) three fractures. Fractures were nine at wrist, three at forearm, two at humerus, two at finger hand bones, one at clavicle, two at tibia, one at ankle, one at toe, and one at pubic symphysis. Fractures occurred after mild or moderate traumatic injuries: fall playing (six) or during physical activity (five biking, two playing football, and one basket), slip (four), collision against a peer (two) or a corner (one), crash (one). Difficulties on fracture healing were not reported. Fractures were not correlated with BMD values.
Conclusion: The prevalence of fractures (30%) in our patients is markedly higher than the reported average for children (in UK from 1.63.6% and in Lombardy, Italy 1.5%). Our study demonstrates a skeletal fragility in MFS children, increasing with age. The knowledge of the epidemiology may be useful to develop preventive strategies.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology