Abstract
BackgroundPathogenic 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.MethodsWe provide the clinical details of two autosomal dominant families with this specific FBN1 variant, which was previously associated with autosomal recessive Marfan syndrome.ResultsClinical 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.ConclusionIn 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.
Highlights
Marfan syndrome (MFS, OMIM #154700) is a multisystem disorder with an estimated prevalence of 1 in 5,000– 10,000
1 (Figure 1a indicates the pedigree at initial presentation of the family, Figure 1b indicates the pedigree after several years follow‐up, Table 1.): The proband (III:2) and her daughter (IV:2) were referred for genetic analysis because of the familial occurrence of abdominal aortic aneurysms (AAA) and a type B aortic dissection at older age
In order to clarify the clinical significance of this variant in heterozygote state, we offered combined clinical and genetic screening to first‐degree relatives of family members with an aneurysm or dissection
Summary
Marfan syndrome (MFS, OMIM #154700) is a multisystem disorder with an estimated prevalence of 1 in 5,000– 10,000. Pathogenic variants in FBN1 may result in classical MFS but have been reported in families presenting with, for example, apparent isolated thoracic aortic aneurysms and dissections (Wang et al, 2013). Pathogenic variants in FBN1 cause autosomal dominant Marfan syndrome but can be found in patients presenting with apparently isolated features of 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. 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
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