3D Printed Personalized External Aortic Root Model in Marfan Syndrome with Isolated Sinus of Valsalva Aneurysm Caused by a Novel Pathogenic FBN1 p.Gly1127Cys Variant

Abstract

The major cause of death in Marfan syndrome (MFS) is cardiovascular complications, particularly progressive dilatation of the proximal aorta, rendering these patients at risk of aortic dissection or fatal rupture. We report a 3D printed personalized external aortic root model for MFS with an isolated sinus of Valsalva aneurysm caused by a novel pathogenic FBN1 variant. A 67-year-old female with a history of lens dislocation and retinal detachment in the left eye was admitted for the evaluation of resting dyspnea several months prior. Transesophageal and transthoracic echocardiography revealed severe aortic valve regurgitation and a large left coronary sinus of Valsalva aneurysm in the proband. Sanger sequencing identified a heterozygous p.Gly1127Cys variant in the FBN1 gene; previously, a mutation at this amino acid position was described as pathogenic (p.Gly1127Ser; rs137854468). A 3D printed personalized external aortic root model based on a multidetector computed tomography scan was constructed to illustrate the location of the ostium of the left main coronary artery on the aneurysm of the left coronary artery cusp. Aortic root replacement with the Bentall procedure matched the exact shape of the 3D printed model. Creation of a 3D printed patient-specific model could be useful in facilitating the development of next-generation medical devices and resolving the risks of postoperative complications and aortic root disease.

Keywords: 3D printed personalized model; FBN1 p.Gly1127Cys variant; Marfan syndrome; Sanger sequencing; aortic root replacement; isolated sinus of Valsalva aneurysm.

Figure 1

Transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) in the proband with Marfan syndrome. TEE (A) and (B) and TTE (C) revealed an isolated sinus of Valsalva aneurysm of the left coronary cusp (arrow) with severe aortic regurgitation. LCC, left coronary cusp; RCC, right coronary cusp; NCC, noncoronary cusp.

Figure 2

3D printed model in the proband with Marfan syndrome. To help understand the anatomic structure before surgery, a 3D printed personalized external aortic root model (A–D) was derived from multi-detector computed tomography to illustrate the location of the ostium of the left main aneurysm of the left coronary cusp (arrow). (E) Aortic root replacement with the Bentall procedure matched the exact shape of the 3D printed model (asterisk). LCC, left coronary cusp; RCC, right coronary cusp; NCC, noncoronary cusp.

Figure 3

Pedigree analysis and sequencing results. (A) Pedigree of the proband (arrow) with Marfan syndrome caused by a heterozygous FBN1 variant and her healthy family members. (B) Sanger sequencing revealed a heterozygous missense variant (NM_000138.4: c.3379G>T; p.Gly1127Cys) of the FBN1 gene in the proband. The variant is highlighted by the red dot. (C) Sequence alignment of the conserved calcium binding epidermal growth factor (cbEGF)-like domain of the FBN1 protein in multiple vertebrate species. The protein sequence of the Gly1127 residue is highly conserved across the compared vertebrate species. It is highlighted in the red box.