Introduction: Marfan syndrome (MFS) and related connective tissue disorders (CTDs) are increasingly recognised. Genetic testing has greatly improved the diagnostic outcome/power over the last two decades. In this study we describe a multicentre cohort of adults with MFS and related CTDs, with a particular focus on results from genetic testing.
Methods: All patients with MFS and related CTDs were identified from the databases of five centres in the canton of Zurich. Echocardiographic and clinical findings including systemic Marfan score, use of medication and genetic results were retrospectively analysed. MFS was diagnosed using the revised Ghent criteria (including FBN1 genetic testing if available); other CTDs (Loeys-Dietz syndrome) were diagnosed by genetic testing only.
Results: A cohort of 103 patients were identified (62 index patients, 41 relatives of family members): 96 patients with MFS and 7 patients with other CTD, 54 males (52%), median age 23 years (range 1–75). The median systemic Marfan score was 5 (range 0–18). Only 40 patients (40/103, 39%) fulfilled criteria for systemic involvement (≥7 points). A history of aortic dissection was present in 14 out of 103 patients (14%). Echocardiographic data were available for all: aortic root enlargement (Z-score ≥2 in adults, Z-score ≥3 in children) was found in 49 patients (48%) and mitral valve prolapse in 64 (62%). Genetic testing had been performed in 80 patients (78%); FBN1 mutations were present in 69 patients (86%); other pathogenic mutations could be identified in seven patients (9%); no disease-causing mutation was found in four patients, three of them fulfilling the Ghent criteria of MFS. Of the mutation-positive patients, 33 had a systemic score of ≥7 and 43 had a systemic score of ≥5. Revised Ghent criteria were fulfilled in 70 patients: in 69 patients with FBN1 mutations and 1 patient with another CTD. Recommended treatment (beta-blocker, angiotensin receptor blocker) was taken by 63% of patients.
Conclusions: In this cohort a high percentage of patients fulfilling the revised Ghent criteria for MFS underwent genetic testing, often leading to or confirming the diagnosis of MFS. Other CTDs could be discriminated best by genetic testing. With respect to the diagnosis of MFS and related CTDs, the usefulness of the systemic score is limited, showing the importance of genetic testing, which enabled definitive diagnosis in 95% of tested patients. Patient education on medical treatment still has to be improved. (Trial registration no: KEK-ZH-Nr. 2013-0241).