The importance of genotype-phenotype correlation in the clinical management of Marfan syndrome

BACKGROUND: Marfan syndrome (MFS) is a disorder of autosomal dominant inheritance, in which aortic root dilation is the main cause of morbidity and mortality. Fibrillin-1 (FBN-1) gene mutations are found in more than 90% of MFS cases. The aim of our study was to summarise variants in FBN-1 and establish the genotype-phenotype correlation, with particular interest in the onset of aortic events, in a broad population of patients with an initial clinical suspicion of MFS. MATERIAL AND METHODS: This single centre prospective cohort study included all patients presenting variants in the FBN-1 gene who visited a Hereditary Aortopathy clinic between September 2010 and October 2016. RESULTS: The study included 90 patients with FBN-1 variants corresponding to 58 non-interrelated families. Of the 57 FBN-1 variants found, 25 (43.9%) had previously been described, 23 of which had been identified as associated with MFS, while the the remainder are described for the first time. For 84 patients (93.3%), it was possible to give a definite diagnosis of Marfan syndrome in accordance with Ghent criteria. 44 of them had missense mutations, 6 of whom had suffered an aortic event (with either prophylactic surgery for aneurysm or dissection), whereas 20 of the 35 patients with truncating mutations had suffered an event (13.6% vs. 57.1%, p < 0.001). These events tended to occur at earlier ages in patients with truncating compared to those with missense mutations, although not significantly (41.33 ± 3.77 vs. 37.5 ± 9.62 years, p = 0.162). CONCLUSIONS: Patients with MFS and truncating variants in FBN-1 presented a higher proportion of aortic events, compared to a more benign course in patients with missense mutations. Genetic findings could, therefore, have importance not only in the diagnosis, but also in risk stratification and clinical management of patients with suspected MFS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13023-017-0754-6) contains supplementary material, which is available to authorized users.