FBN1 Mutation Does Not Influence Handling of Patients with Confirmed Marfan Syndrome

Background: Marfan syndrome (MFS) is an inherited connective-tissue disorder, caused by a mutation in the FBN1 gene. Diagnosis of MFS relies on revised Ghent criteria (RGC) with three cardinal clinical symptoms: dilatation of sinus of Valsalva (SV), ectopia lentis (EL), and systemic manifestation (Sys). We analyzed prevalence and age of manifestation of cardinal symptoms according to RGC in patients with and without FBN1. Finally, we also wanted to evaluate whether it is suggestive to distinguish patients with or without FBN1 mutation concerning regular follow-up and prophylaxis. Methods: We investigated 215 patients (10.6 ± 5.4 years) with genetically or clinically suggestive (42%) or assumed and ruled out (58%) MFS and subjected them to a standardized diagnostic program. We performed echo and clinical examination including all symptoms involved in the RGC. We also did genetic analysis whenever possible and available. Results: We performed genetic analysis in 71 of 215 patients with a detection rate of 78% for FBN1. We did not find any significant differences concerning prevalence or age of manifestation of SV, EL, or Sys by comparing patients with or without FBN1 mutation. Table 1: Prevalence and age of manifestation of dilatation of sinus of Valsalva (SV), ectopia lentis (EL) and systemic manifestation (Sys) FBN1 pos. (%) FBN1 neg. (%) FBN1 pos. (y ± SD) FBN1 neg. (y ± SD) p SV 69% (38/55) 73%(24/33) 9.51 ± 4.98 10.34 ± 6.17 0.559 EL 27% (15/55) 18%(6/33) 7.40 ± 4.92 5.00 ± 2.87 0.283 Sys 38% (21/55) 76%(25/33) 11.18 ± 4.83 12.99 ± 4.00 0.171 Conclusion: None of the three clinical cardinal symptoms showed a significant variation between patients with or without FBN1. Both prevalence and mean age of manifestation were almost similar in the two groups. Therefore, there is no need to differentiate between FBN1 mutation negative or positive patients, concerning handling, examinations, and prophylaxis. A regular follow-up is as important for MFS patients with FBN1 mutation as for those without.