Ocular, cardiovascular, and genetic characteristics and their associations in children with Marfan syndrome and related fibrillinopathies.

Purpose: Congenital ectopia lentis (CEL) and heart abnormalities are common clinical symptoms in patients with Marfan syndrome (MFS) and related fibrillinopathies, which is caused by mutations in fibrillin-1 (FBN1) gene. This study aims to explore the ocular and cardiovascular characteristics and their association with genotype in children with MFS and related fibrillinopathies.

Methods: Seventy-nine children diagnosed with CEL and with FBN1 mutations confirmed via whole-exome sequencing were included for genotypes and phenotypes analysis. The axial length (AL), corneal curvature, and refractive status were included for ocular phenotypes analysis. The cardiovascular examination was performed by echocardiography, and aortic root Z score was calculated to evaluate the severity of aortic dilatation. The heart disorders were classified as aortic root dilatation, valvular disorders, and others. Both the ocular and cardiac manifestations were collected for comprehensive analysis and compared among patients with different genotypes, including the mutation involving cysteine substitution or mutation in different regions.

Results: In CEL children with FBN1 mutations, 77.2% patients could be diagnosed as MFS. It was observed that children with mutations in exons 22-42 had significant higher aortic root Z score (P = 0.003) and higher incidence of cardiovascular disorders (P = 0.004). Additionally, children with cysteine substitution mutations had significant higher aortic root Z score (P = 0.011), and the aortic root Z score was positively associated with axial length (AL) in children under 6 years old (P = 0.035). Those with long AL (≥ 26 mm) had significant higher incidence of valve disorders (P = 0.023). In addition, nearly half the children with CEL (46.8%) were diagnosed with cardiovascular disease for the first time.

Conclusions: CEL children with FBN1 mutations involving cysteine substitution or mutations in exons 22-42 or with long AL had higher risks of severe cardiovascular complications. Knowing the phenotype may help in anticipating severe cardiovascular disease in CEL patients.