The phenotypic heterogeneity of patients with Marfan-related disorders and their variant spectrums

Marfan syndrome (MFS) and Loeys–Dietz syndrome (LDS) are the connective tissue disorders characterized by aortic root aneurysm and/or dissection and various additional features. We evaluated the correlation of these mutations with the phenotypes and determined the clinical applicability of the revised Ghent criteria. The mutation spectrum and phenotypic heterogeneities of the 83 and 5 Korean patients with suspected MFS and LDS were investigated as a retrospective manner. In patients with suspected MFS patients, genetic testing was conducted in half of 44 patients who met the revised Ghent criteria clinically and half of 39 patients who did not meet these criteria. Fibrillin1 gene (FBN1) variants were detected in all the 22 patients (100%) who met the revised Ghent criteria and in 14 patients (77.8%) who did not meet the revised Ghent criteria (P = .0205). Patients with mutations in exons 24–32 were diagnosed at a younger age than those with mutations in other exons. Ectopia lentis was more common in patients with missense mutations than in patients with other mutations. Aortic diameter was greater in patients with missense mutations in cysteine residues than in patients with missense mutations in noncysteine residues. Five LDS patients had either TGFBR1 or TGFBR2 variants, of which 1 patient identified TGFBR1 variant uncertain significance. The revised Ghent criteria had very high clinical applicability for detecting FBN1 variants in patients with MFS and might help in selecting patients with suspected MFS for genetic testing.