Low yield of genetic testing for known vascular connective tissue disorders in patients with fibromuscular dysplasia.
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.
Cleveland Clinic Heart and Vascular Institute and the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA.
Stacey L
SL
Poloskey
Esther Sh
ESh
Kim
Ruchi
R
Sanghani
Adeeb H
AH
Al-Quthami
Patricia
P
Arscott
Rocio
R
Moran
Christina M
CM
Rigelsky
Heather L
HL
Gornik
D000328:Adult; D000784:Aortic Dissection / Q000235:genetics*; D001014:Aortic Aneurysm / Q000235:genetics*; D003238:Connective Tissue / Q000503:physiopathology; D003240:Connective Tissue Diseases / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005352:Fibromuscular Dysplasia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012306:Risk
D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I