Low yield of genetic testing for known vascular connective tissue disorders in patients with fibromuscular dysplasia

• Published in: Vascular medicine (London, England) Vol. 17; no. 6; pp. 371 - 378
• Main Authors: Poloskey, Stacey L, Kim, Esther SH, Sanghani, Ruchi, Al-Quthami, Adeeb H, Arscott, Patricia, Moran, Rocio, Rigelsky, Christina M, Gornik, Heather L
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.12.2012; Sage Publications Ltd
• Subjects: Adult; Aneurysm, Dissecting - genetics; Aortic Aneurysm - genetics; Connective Tissue - physiopathology; Connective Tissue Diseases - complications; Connective Tissue Diseases - diagnosis; Connective Tissue Diseases - genetics; Female; Fibromuscular Dysplasia - complications; Fibromuscular Dysplasia - diagnosis; Fibromuscular Dysplasia - genetics; Genetic Testing; Humans; Male; Middle Aged; Phenotype; Protein-Serine-Threonine Kinases - metabolism; Receptors, Transforming Growth Factor beta - metabolism; Risk; peripheral vascular diseases; fibromuscular dysplasia; genetics
• ISSN: 1358-863X; 1477-0377
• DOI: 10.1177/1358863X12459650

Patients with fibromuscular dysplasia (FMD) may have clinical features consistent with Mendelian vascular connective tissue disorders. The yield of genetic testing for these disorders among patients with FMD has not been determined. A total of 216 consecutive patients with FMD were identified. Clinical characteristics were collected and genetic test results reviewed for abnormalities in the following genes: transforming growth factor-β receptor 1 and 2 (TGFβR1 and TGFβR2), collagen 3A1, fibrillin-1, smooth muscle α-actin 2, and SMAD3. A total of 63 patients (63/216; 29.2%) were referred for genetic counseling with testing performed in 35 (35/63; 55.6%). The percentage of patients with a history of arterial or aortic dissection, history of aortic aneurysm, systemic features of a connective tissue disorder, and a family history of sudden death was significantly larger in the group that underwent genetic testing (62.9% vs 18.2%, p < 0.001; 8.6% vs 1.7%, p = 0.02; 51.4% vs 17.1%, p < 0.001; and 42.9% vs 22.7%, p = 0.04, respectively). Two patients were found to have distinct variants in the TGFβR1 gene (c.611 C>T, p.Thr204lle and c.1285 T>C, p.Tyr429His). The yield of genetic testing for vascular connective tissue disorders was low in a high-risk subset of FMD patients. However, two patients with a similar phenotype had novel and distinct variants in the TGFβR1 gene, a finding which merits further investigation.