Autosomal dominant Marfan syndrome caused by a previously reported recessive FBN1 variant

Abstract

Background: Pathogenic variants in FBN1 cause autosomal dominant Marfan syndrome but can also be found in patients presenting with apparently isolated features of Marfan syndrome. Moreover, several families with autosomal recessive Marfan syndrome caused by pathogenic variants in FBN1 have been described. The aim of this report was to underline the clinical variability that can be associated with the pathogenic variant c.1453C>T, p.(Arg485Cys) in FBN1.

Methods: We provide the clinical details of two autosomal dominant families with this specific FBN1 variant, which was previously associated with autosomal recessive Marfan syndrome.

Results: Clinical data of 14 individuals carrying this variant from these two families were collected retrospectively. In both families, the diagnosis of autosomal dominant Marfan syndrome was established based on the characteristics of the variant and the phenotype which includes aortic aneurysms and dissections. Of interest, in one of the families, multiple relatives were diagnosed with early onset abdominal aortic aneurysms.

Conclusion: In conclusion, FBN1 variant c.1453C>T, p.(Arg485Cys) is a pathogenic variant that can cause autosomal dominant Marfan syndrome characterized by a high degree of clinical variability and apparently isolated early onset familial abdominal aortic aneurysms.

Keywords: FBN1; Marfan syndrome; abdominal aortic aneurysm; autosomal dominant inheritance; autosomal recessive inheritance; clinical heterogeneity.

Figure 1

Pedigrees of families 1 and 2. (a) indicates the pedigree at initial presentation of family 1, (b) indicates the pedigree of this family after several years follow‐up. (c) Shows family 2. The proband is indicated with an arrow