Relation between genotype and left-ventricular dilatation in patients with Marfan syndrome

Abstract

Cardiovascular manifestations in patients with Marfan syndrome (MFS) are related to aortic and valvular abnormalities. However, dilatation of the left ventricle (LV) can occur, even in the absence of aortic surgery or valvular abnormalities. We evaluated genetic characteristics of patients with MFS with LV dilatation. One hundred eighty-two patients fulfilling the MFS criteria, without valvular abnormalities or previous aortic surgery, with a complete FBN1 analysis, were studied. FBN1 mutations were identified in over 81% of patients. Twenty-nine patients (16%) demonstrated LV dilatation (LV end diastolic diameter corrected for age and body surface area >112%). FBN1-positive patients carrying a non-missense mutation more often had LV dilatation than missense mutation carriers (14/74 versus 5/75; p<0.05). Finally, FBN1-negative MFS patients significantly more often demonstrated LV dilatation than FBN1-positive patients (10/33 versus 19/149; p<0.05). It is concluded that LV dilatation in MFS patients is more often seen in patients with a non-missense mutation and in those patients without an FBN1 mutation. Therefore physicians should be aware of the possibility of LV dilatation in these patients even in the absence of valvular pathology.

Keywords: DHPLC; FBN1-mutation; FBNI; Genetics; Genotype–phenotype relation; LV; LVEDD; Left ventricular dilatation; M-mode; MFS; MLPA; Marfan syndrome; SD; TGFBR1; TGFBR2; TGFβ; denaturing high performance liquid chromatography; fibrillin-1 gene; left ventricle; left ventricular end diastolic dimension; motion mode; multiplex ligation-dependent probe amplification; standard deviation; transforming growth factor beta; transforming growth factor-β receptor 1 gene; transforming growth factor-β receptor 2 gene.