Is there a hereditary component to aneurysms, particularly in older adults with a family history of aneurysms and a history of spinal issues?

Are Aneurysms Hereditary?

Yes, aneurysms have a strong hereditary component, with first-degree relatives of patients with aneurysms carrying 2-18 times the risk of developing aneurysms compared to the general population, depending on the type and location of aneurysm. 1, 2

Abdominal Aortic Aneurysms (AAA)

Family Risk Quantification

• First-degree male relatives of patients with AAA have a relative risk of 18 for developing AAA themselves, suggesting a single dominant gene effect. 1
• Among offspring of patients with ruptured AAA, 21% of sons older than 45 years and 4% of daughters older than 42 years had aortic enlargement to at least 3.0 cm diameter. 1
• In surgical series, 15-28% of patients undergoing AAA repair had first-degree relatives with aneurysms, compared to only 2% of age-matched controls. 1
• Brothers of AAA patients show the highest prevalence at 32% lifetime risk, with ultrasonographic screening identifying AAA in 25% of brothers aged 50 years or older. 3

Genetic Mechanisms

• Recent genome-wide association studies have identified specific genetic markers within the DAB2IP and LRP1 genes that increase AAA risk, though the exact mechanisms remain under investigation. 4
• The 9p21 genetic marker, associated with other vascular diseases, is also strongly linked to AAA development. 4

Thoracic Aortic Aneurysms (TAA)

Syndromic Forms

• Marfan syndrome (FBN1 gene mutations), Loeys-Dietz syndrome (TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 mutations), and vascular Ehlers-Danlos syndrome (COL3A1 mutations) are well-established hereditary causes of thoracic aortic disease. 1, 5
• These conditions follow autosomal dominant inheritance, conferring up to 50% risk to offspring. 5

Non-Syndromic Familial TAA

• Pathogenic variants in ACTA2, MYH11, and MYLK cause familial thoracic aortic aneurysm and dissection (FTAAD) without obvious syndromic features. 1, 5
• 11-19% of patients undergoing thoracic aortic aneurysm repair have a first-degree relative with similar disease. 5

Critical Risk Features

• TAA presenting at age less than 60 years strongly suggests hereditary disease. 1
• Family history of either TAA or peripheral/intracranial aneurysms in first- or second-degree relatives indicates genetic predisposition. 1
• Certain genetic mutations (particularly TGFBR1 and TGFBR2) predispose to dissection at smaller aortic diameters (<5.0 cm) or even normal diameters. 1, 5

Intracranial (Brain) Aneurysms

Family Risk Assessment

• First-degree relatives of patients with familial intracranial aneurysm syndrome have approximately 8% risk of harboring an unruptured aneurysm with a relative risk of 4.2. 2
• The risk is particularly elevated with multiple affected family members—having three or more affected relatives triples the risk of subarachnoid hemorrhage. 2
• Prevalence in individuals with family history ranges from 1.9% to 5.9% compared to the general population. 2

Associated Genetic Syndromes

• Autosomal dominant polycystic kidney disease carries a 10-11.5% prevalence of cerebral aneurysms. 2, 6
• Type IV Ehlers-Danlos syndrome, Marfan syndrome, coarctation of the aorta, and bicuspid aortic valve are all associated with increased intracranial aneurysm risk. 2

Shared Genetic Basis Across Aneurysm Types

Cross-Location Risk

• Evidence demonstrates that aortic and cerebral aneurysm formation may share common genetic predisposition in some families, with pedigree analyses showing autosomal dominant inheritance patterns affecting both locations. 7
• 10.5% of patients with cerebral aneurysms have a family history of aortic aneurysm, establishing a bidirectional relationship. 6, 7
• Patients with aortic aneurysms have increased risk of harboring cerebral aneurysms, justifying screening in both directions. 6

Clinical Implications for Screening

Who Should Be Screened

• All first-degree relatives of patients with AAA, TAA, or intracranial aneurysms should undergo screening, regardless of symptoms. 1, 2, 5
• For intracranial aneurysms: Strong screening recommendation (Class I) for individuals with two or more first-degree relatives with history of aneurysmal subarachnoid hemorrhage or unruptured intracranial aneurysm. 2
• For thoracic aortic disease: Immediate screening with transthoracic echocardiography for all first-degree relatives of affected patients. 1, 5
• For AAA: Brothers of affected patients warrant particularly aggressive screening given their 32% lifetime risk. 3

Screening Intervals

• For intracranial aneurysms with ≥2 affected first-degree relatives: MRA screening every 5-7 years from age 20 to 80 years. 2
• For thoracic aortic disease with normal initial imaging: Repeat imaging every 3-5 years initially, with more frequent surveillance as patients age into typical risk periods (30s-40s). 5

Genetic Testing Strategy

• Genetic testing should be pursued for established aortopathy genes including FBN1, TGFBR1, TGFBR2, COL3A1, ACTA2, and MYH11 when familial patterns are identified. 1, 5
• If a pathogenic variant is identified, only relatives carrying the mutation require ongoing surveillance, making cascade testing cost-effective. 1, 5
• The affected family member should ideally undergo genetic testing first to guide cascade testing of relatives. 5

Critical Risk Factor Modification

Non-Negotiable Interventions

• Smoking cessation is mandatory—smoking is one of the strongest modifiable risk factors for both aneurysm formation and rupture across all locations. 1, 2, 6
• Blood pressure control is essential, with antihypertensive medication reducing diastolic blood pressure by 6 mmHg producing a 42% reduction in stroke incidence. 2, 6
• Avoid sympathomimetic drugs including cocaine and phenylpropanolamine, which are implicated as causes of subarachnoid hemorrhage. 2
• Limit alcohol consumption, as heavy use is an independent risk factor for subarachnoid hemorrhage. 2

Important Caveats

Age and Presentation

• Familial aneurysms can present at younger ages than sporadic cases, making age-based screening thresholds less reliable in hereditary disease. 1, 5
• Advancing age remains a major risk factor, with AAA prevalence reaching 5.9% in men aged 80-85 years and 4.5% in women over 90 years. 1

Gender Considerations

• Male gender confers higher risk for AAA, but female first-degree relatives appear to be at similar risk and should not be excluded from screening. 1
• Women have a 1.24 times higher incidence of aneurysmal subarachnoid hemorrhage compared to men. 2
• Patients with familial aneurysms were more often female (35%) than those without (14%). 1

Rupture Risk in Familial Cases

• Familial AAA cases are more likely to have ruptured AAA (8%) than sporadic cases (2.4%), emphasizing the importance of early detection in at-risk families. 3
• Growing aneurysms have an 18.5% annual hemorrhage rate compared to 0.2% for stable aneurysms in patients with family history. 2