Diagnosis in children with Marfan syndrome: red flags for early identification

Background Marfan syndrome (MFS) is a multisystemic disorder caused by pathogenic (P) variants in the fibrillin-1 gene ( FBN1 ), associated with life-threatening cardiovascular complications. Early diagnosis enables preventive interventions, yet recognition in children can be challenging. Objective To identify common diagnostic traits in children with MFS that may assist general paediatricians in the recognition of children with MFS and lead to early detection of the disease. Study design This retrospective study included 129 children who underwent genetic testing due to a suspicion of MFS. Personal and family history, clinical features and echocardiographic results were compared between those children where a (likely)P ((L)P) variant in FBN1 was found (n=64) and those with normal genetic testing (n=65). Results Children carrying a (L)P variant in FBN1 were significantly younger (7.6±4.2 years vs 11.2±4.5 years, p<0.001) and more often met the revised Ghent criteria based on clinical features (60.9% vs 1.5%, p<0.001). Six key predictors of MFS were identified: percentile height (OR 1.1 (CI 1.0 to 1.1), p<0.001), aortic root z-score ≥2 (OR 2.1 (CI 1.3 to 3.4), p=0.002), positive family history of aortic aneurysms/dissections (positive family history) (OR 8.0 (CI 1.7 to 37.0), p=0.008), increased arm-span (OR 21.0 (CI 1.0 to 443.1), p=0.050), hindfoot deformity (OR 145.7 (CI 7.7 to 2766.6), p<0.001) and ectopia lentis (EL)(41% vs 0%, p<0.001). Conclusions In children with clinically suspected MFS, a positive family history, increased aortic root z-score, EL, tall stature, increased arm-span and hindfoot deformity were significant predictors of a molecularly confirmed diagnosis of MFS.