Family history of aortic dissection is not a risk factor in Marfan syndrome with a FBN1 gene mutation

Abstract Background A history family of aortic dissection was considered as a risk factor for aortic dissection in patients with Marfan syndrome with a FBN1 mutation. Objectives Evaluate whether a family history of aortic dissection is a risk marker for dissection in this population Methods Retrospective study of patients coming to the reference centre between 1996 and 2018, carrying a FBN1 gene mutation. Pedigrees were obtained for each patient, and familial screening actively pursued. Patients with a family history of aortic dissection were compared with patients without family history of aortic dissection. Results 1700 patients (age 33.2 (±17) years, 51% women) with a FBN1 gene mutation were included. 145 (8,5%) patients underwent aortic dissection at a mean age of 37.9 (±11.4) years and 323 (19%) patients had been operated at 33.8 (±13.9) years. 481 patients had a family history of aortic dissection, including 38 who dissected themselves, and 88 who underwent surgery. 1219 had no family history of aortic dissection, including 107 who dissected themselves, and 235 who underwent surgery. Therefore, the personal risk for aortic dissection was similar in patients with and without a family history of aortic dissection (38/481, i.e. 7.9% vs 107/1219, i.e. 8.8%), as was the personal risk for prophylactic aortic surgery (88/481, i.e. 18.3% vs. 253/1219, i.e. 17.2%), and the risk for either aortic dissection or prophylactic aortic surgery (118/481, i.e. 24.5% vs. 328/1219, i.e. 26.9%). Conclusions In Marfan syndrome with a FBN1 gene mutation, a family history of aortic dissection is not a marker of aortic disease severity. FUNDunding Acknowledgement Type of funding sources: None.

Download Full-text

Fatal Aortic Dissection in a Patient With a Family History of Marfan Syndrome

Obstetrics and Gynecology ◽

10.1097/aog.0b013e3181743312 ◽

2008 ◽

Vol 112 (2, Part 2) ◽

pp. 472-475 ◽

Cited By ~ 3

Author(s):

Meredith L. Birsner ◽

John L. Farber ◽

Vincenzo Berghella

Keyword(s):

Family History ◽

Aortic Dissection ◽

Marfan Syndrome ◽

History Of

Download Full-text

Clinical implications of identifying pathogenic variants in aortic dissection patients with whole exome sequencing

10.1101/497917 ◽

2018 ◽

Author(s):

Brooke N. Wolford ◽

Whitney E. Hornsby

Keyword(s):

Family History ◽

Aortic Dissection ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Family Members ◽

Aortic Disease ◽

Thoracic Aortic Dissection ◽

Pathogenic Variants ◽

Whole Exome ◽

History Of

ABSTRACTBackgroundThoracic aortic dissection is an emergent life-threatening condition. Routine screening for genetic variants causing thoracic aortic dissection is not currently performed for patients or their family members.MethodsWe performed whole exome sequencing of 240 patients with thoracic aortic dissection (n=235) or rupture (n=5) and 258 controls matched for age, sex, and ancestry. Blinded to case-control status, we annotated variants in 11 genes for pathogenicity.ResultsTwenty-four pathogenic variants in 6 genes (COL3A1, FBN1, LOX, PRKG1, SMAD3, TGFBR2) were identified in 26 individuals, representing 10.8% of aortic cases and 0% of controls. Among dissection cases, we compared those with pathogenic variants to those without and found that pathogenic variant carriers had significantly earlier onset of dissection (41 vs. 57 years), higher rates of root aneurysm (54% vs. 30%), less hypertension (15% vs. 57%), lower rates of smoking (19% vs. 45%), and greater incidence of aortic disease in family members. Multivariable logistic regression showed significant risk factors associated with pathogenic variants are age <50 [odds ratio (OR) = 5.5; 95% CI: 1.6-19.7], no history of hypertension (OR=5.6; 95% CI: 1.4-22.3) and family history of aortic disease (mother: OR=5.7; 95% CI: 1.4-22.3, siblings: OR=5.1; 95% CI 1.1-23.9, children: OR=6.0; 95% CI: 1.4-26.7).ConclusionsClinical genetic testing of known hereditary thoracic aortic dissection genes should be considered in patients with aortic dissection, followed by cascade screening of family members, especially in patients with age-of-onset of aortic dissection <50 years old, family history of aortic disease, and no history of hypertension.

Download Full-text

AORTIC DISSECTION IN THE SETTING OF PREGNANCY AND FAMILY HISTORY OF MARFAN SYNDROME

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(15)60654-4 ◽

2015 ◽

Vol 65 (10) ◽

pp. A654

Author(s):

Adam M. Mizeracki ◽

Rami Khouzam

Keyword(s):

Family History ◽

Aortic Dissection ◽

Marfan Syndrome ◽

History Of

Download Full-text

Clinical Implications of Identifying Pathogenic Variants in Individuals With Thoracic Aortic Dissection

Circulation Genomic and Precision Medicine ◽

10.1161/circgen.118.002476 ◽

2019 ◽

Vol 12 (6) ◽

Cited By ~ 10

Author(s):

Brooke N. Wolford ◽

Whitney E. Hornsby ◽

Dongchuan Guo ◽

Wei Zhou ◽

Maoxuan Lin ◽

...

Keyword(s):

Family History ◽

Aortic Dissection ◽

Age Of Onset ◽

Family Members ◽

Aortic Disease ◽

Pathogenic Variant ◽

Carrier Status ◽

Thoracic Aortic Dissection ◽

Pathogenic Variants ◽

History Of

Background: Thoracic aortic dissection is an emergent life-threatening condition. Routine screening for genetic variants causing thoracic aortic dissection is not currently performed for patients or family members. Methods: We performed whole exome sequencing of 240 patients with thoracic aortic dissection (n=235) or rupture (n=5) and 258 controls matched for age, sex, and ancestry. Blinded to case-control status, we annotated variants in 11 genes for pathogenicity. Results: Twenty-four pathogenic variants in 6 genes (COL3A1, FBN1, LOX, PRKG1, SMAD3, and TGFBR2) were identified in 26 individuals, representing 10.8% of aortic cases and 0% of controls. Among dissection cases, we compared those with pathogenic variants to those without and found that pathogenic variant carriers had significantly earlier onset of dissection (41 versus 57 years), higher rates of root aneurysm (54% versus 30%), less hypertension (15% versus 57%), lower rates of smoking (19% versus 45%), and greater incidence of aortic disease in family members. Multivariable logistic regression showed that pathogenic variant carrier status was significantly associated with age <50 (odds ratio [OR], 5.5; 95% CI, 1.6–19.7), no history of hypertension (OR, 5.6; 95% CI, 1.4–22.3), and family history of aortic disease (mother: OR, 5.7; 95% CI, 1.4–22.3, siblings: OR, 5.1; 95% CI, 1.1–23.9, children: OR, 6.0; 95% CI, 1.4–26.7). Conclusions: Clinical genetic testing of known hereditary thoracic aortic dissection genes should be considered in patients with a thoracic aortic dissection, followed by cascade screening of family members, especially in patients with age-of-onset <50 years, family history of thoracic aortic disease, and no history of hypertension.

Download Full-text

6126Peripheral aneurysms in Marfan patients are common and are related to age and advanced aortic disease

European Heart Journal ◽

10.1093/eurheartj/ehz746.0152 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

L Mila ◽

G Teixido Tura ◽

C Granato ◽

J Limeres ◽

L Servato ◽

...

Keyword(s):

Aortic Dissection ◽

Ct Angiography ◽

Marfan Syndrome ◽

Aortic Surgery ◽

Aortic Disease ◽

Arterial System ◽

Whole Body ◽

Fbn1 Mutation ◽

Peripheral Aneurysms

Abstract Background Peripheral aneurysms are not included in the diagnostic criteria for Marfan syndrome (MFS); however, their real prevalence in MFS is unknown. Furthermore, they are commonly seen in other genetic entities such as Loeys-Dietz syndrome. We aimed to investigate the prevalence of peripheral aneurysm in Marfan syndrome. Methods Patients with clinical criteria of Marfan syndrome and identified FBN1 mutation were evaluated. Only patients with either MRI or CT angiography assessing peripheral vessels were included in this study. MRI and CT angiography studies were retrospectively evaluated to detect the presence of peripheral aneurysms. Aortic dissection-related arterial dilations were excluded. Aortic events and those related to aneurysm complications were collected during follow-up. Results Two hundred and nine patients with Marfan and FBN1 mutation were evaluated. Of these 136 (65.1%) had undergone either MRA or CTA with peripheral artery study during follow-up. Mean age at the last follow-up visit was 42.4±14.1yrs; 54.4% were men, and mean follow-up 7.3±3.1 years. Sixty-six aneurysms were identified in 42 (30.9%) patients. The most common locations were the iliac arteries in 23. The rest were: renal (7), vertebral (5), splenic (5), coeliac (3), brachiocephalic (1), subclavian (3), carotid (3), axillary (2), internal mammary (3), femoral (2), hypogastric (3), bronchial (2), coronary (1), hepatic (1), lumbar (1), gastroduodenal (1) and popliteal (1). Twenty-six patients (61.9%) had more than one peripheral aneurysm, and only 4 required surgery. Patients with peripheral aneurysms were older (47.2±14.3yrs vs 40.2±13.6yrs, p=0.06) and more frequently men (69.0% vs 47.9% p=0.026). Although patients with peripheral aneurysms did not more frequently have aortic dissection (16.7% vs 17.0%, p=0.586), they did more frequently have aortic surgery (73.8% vs 47.9% p=0.05). Conclusions Peripheral aneurysms are present in one third of Marfan syndrome patients and are related to age and more advanced aortic disease. Systematic use of whole-body vascular assessment in Marfan patients can provide a comprehensive evaluation of the entire arterial system, identifying other sites of vascular involvement at risk of potential complications, and the subgroup of patients with more aggressive vascular disease expression.

Download Full-text