Analysis of phenotype and genotype information for the diagnosis of Marfan syndrome

Sheikhzadeh S, Kade C, Keyser B, Stuhrmann M, Arslan‐Kirchner M, Rybczynski M, Bernhardt AM, Habermann CR, Hillebrand M, Mir T, Robinson PN, Berger J, Detter C, Blankenberg S, Schmidtke J, von Kodolitsch Y. Analysis of phenotype and genotype information for the diagnosis of Marfan syndrome. Marfan syndrome is considered a clinical diagnosis. Three diagnostic classifications comprising first, Marfan genotype with a causative FBN1 gene mutation; second, Marfan phenotype with clinical criteria of the original Ghent nosology (Ghent‐1); and third, phenotype with clinical criteria of its current revision (Ghent‐2) in 300 consecutive persons referred for confirmation or exclusion of Marfan syndrome (150 men, 150 women aged 35 ± 13 years) were used. Sequencing of TGBR1/2 genes was performed in 128 persons without FBN1 mutation. Marfan genotype was present in 140, Ghent‐1 phenotype in 139, and Ghent‐2 phenotype in 124 of 300 study patients. Marfan syndrome was confirmed in 94 and excluded in 129 persons consistently by all classifications, but classifications were discordant in 77 persons. With combined genotype and phenotype information confirmation of Marfan syndrome was finally achieved in 126 persons by Ghent‐1 and in 125 persons by Ghent‐2 among 140 persons with Marfan genotype, and exclusion was accomplished in 139 persons by Ghent‐1 and in 141 persons by Ghent‐2 among 160 persons without Marfan genotype. In total, genotype information changed final diagnoses in 22 persons with Ghent‐1, and in 32 persons with Ghent‐2. It is concluded that genotype information is essential for diagnosis or exclusion of Marfan syndrome.