Is there a familial predisposition to aneurysm (abnormal dilation of an artery)?

From the Guidelines

Yes, aneurysms can run in families, with first-degree relatives of someone with an aneurysm having approximately 2-4 times higher risk of developing one compared to the general population. The risk of aneurysm occurrence is higher in families with a history of two or more members having aneurysms or subarachnoid hemorrhage (SAH) 1. Certain genetic disorders, such as Autosomal Dominant Polycystic Kidney Disease, Ehlers-Danlos syndrome, and Marfan syndrome, also increase aneurysm risk.

Key Points to Consider

• The prevalence of familial occurrence of intracranial aneurysms (IAs) ranges from 7% to 20% 1.
• First-degree relatives of those with a history of SAH have a higher likelihood of aneurysm detection, with 4% (95% CI, 2.6%–5.8%) of such relatives found to have a unruptured intracranial aneurysm (UIA) on screening imaging 1.
• Factors that increase the likelihood of aneurysm detection in those with familial risk include older age, female sex, cigarette smoking, history of hypertension, higher lipid levels, higher fasting glucose, family history of polycystic kidney disease, and family history of SAH or aneurysm in ≥ 2 relatives 1.
• The American Heart Association/American Stroke Association recommends screening with imaging tests like MRA or CTA for patients with two family members with IA or SAH, particularly those with a history of hypertension, smoking, and female sex 1.

Recommendations for Screening and Management

• Patients with a family history of aneurysms should discuss this with their doctor, who may recommend screening with imaging tests like MRA or CTA, especially if two or more close relatives have had aneurysms.
• Managing controllable risk factors like high blood pressure, avoiding smoking, limiting alcohol, and maintaining a healthy lifestyle can help reduce overall risk.
• The genetic link exists because inherited connective tissue disorders or blood vessel wall weaknesses can make arterial walls more susceptible to ballooning under pressure.

Important Considerations

• The inheritance patterns of IAs are unclear, but autosomal dominance transmission is suspected to be the most common mode of inheritance 1.
• Genome-wide association studies have identified several genetic variants associated with an increased risk of aneurysm occurrence, including the CDKN2BAS and SOX17 genes 1.

From the Research

Aneurysm and Family History

• Aneurysms can run in families, with studies suggesting a prevalence of familial cerebral aneurysms ranging from 5-28% 2.
• The pattern of inheritance is unknown, but research suggests that familial cerebral aneurysms tend to occur at the same or mirror site within families, and tend to rupture within the same decade in families, and within five years of each other in identical twins 2.
• A study found that 10% of patients report an aneurysm in a first-degree family member, and that the incidence of family history among different ethnic groups is similar, with 19.4% in Caucasians, 20.6% in African-Americans, and 21.6% in Hispanics 3.

Genetic Basis

• Research suggests that aortic and cerebral aneurysm formation may share a common genetic predisposition in some families, with pedigree analyses showing an inheritance pattern likely to represent autosomal dominance with variable penetrance 4.
• At least six genetic variants have been associated with abdominal aortic aneurysm (AAA) in genome-wide association studies, including CDKN2BAS1, DAB2IP, LDLR, LRP1, SORT1, and IL6R 5.
• However, these variants have not been replicated in multiple cohorts, nor have they been clearly shown to be disease causative, highlighting the need for further research into the genetic causes of aneurysm disease.

Demographic Factors

• Studies have found that familial cerebral aneurysms are more common in women, with 80% of familial aneurysms occurring in women versus 59% of sporadic aneurysms 6.
• The overrepresentation of women with familial aneurysms is most pronounced below the age of 50, where 78% of patients with familial aneurysms are women compared with 45% for sporadic aneurysms 6.
• Research also suggests that familial aneurysms in females tend to rupture at the same site within families, and that multiple familial aneurysms occur mainly in women 6.