Skip to main content
main-content

01.12.2018 | Research | Ausgabe 1/2018 Open Access

Orphanet Journal of Rare Diseases 1/2018

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

Zeitschrift:
Orphanet Journal of Rare Diseases > Ausgabe 1/2018
Autoren:
Víctor Manuel Becerra-Muñoz, Juan José Gómez-Doblas, Carlos Porras-Martín, Miguel Such-Martínez, María Generosa Crespo-Leiro, Roberto Barriales-Villa, Eduardo de Teresa-Galván, Manuel Jiménez-Navarro, Fernando Cabrera-Bueno
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s13023-017-0754-6) contains supplementary material, which is available to authorized users.

Abstract

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.
Zusatzmaterial
Additional file 1: Table S1. Variants in FBN-1 and phenotypic characteristics of the carrier patients. (DOCX 79 kb)
13023_2017_754_MOESM1_ESM.docx
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2018

Orphanet Journal of Rare Diseases 1/2018 Zur Ausgabe