Late diagnosis of Loeys-Dietz syndrome in a cystic fibrosis patient: A case report

Cystic fibrosis (CF) already entails high treatment burden. Co-occurrence with connective-tissue aortopathy is exceptionally rare. We report a 23-year-old woman with CF due to CFTR c.1521_1523delCTT (p.Phe508del) apparent homozygosity. She underwent multiple orthopedic procedures from childhood. On transfer to our CF center, dysmorphic features (bifid uvula, hypertelorism) prompted genetic evaluation and a diagnosis of Loeys–Dietz syndrome (LDS) due to a heterozygous TGFBR2 [Exon 8,c.1678G > C, p.(Ala560pro), heterozygot] pathogenic variant. Imaging showed a 48 mm aortic root (≈ + 6 z). Valve-sparing aortic root repair (David procedure) was performed with good postoperative recovery under ongoing CFTR-modulator therapy (elexacaftor/tezacaftor/ivacaftor). In CF patients with disproportionate musculoskeletal or craniofacial findings, consider syndromic aortopathy and pursue genetics early. Timely LDS recognition enables elective aortic repair at smaller diameters and may prevent dissection. This case underscores the value of cross-disciplinary screening for dual genetic diagnoses to optimize outcomes in complex phenotypes.