SNP Shot: Genomic Insights

Familial thoracic aortic aneurysm and dissection (familial TAAD) is a condition affecting the aorta, the body's main artery carrying blood from the heart. In familial TAAD, problems arise in the thoracic aorta, the part of the aorta located in the chest, near the heart. Other arteries carrying blood away from the heart can also be affected.

In familial TAAD, the aorta weakens and stretches (aortic dilatation), potentially forming a bulge in the artery wall (aneurysm). Aortic dilatation can also lead to a tear in the aorta's layers (aortic dissection), allowing blood to flow between them abnormally. These aortic issues are life-threatening, potentially reducing blood flow to vital organs like the brain or causing the aorta to rupture (break open).

The timing and occurrence of aortic abnormalities in familial TAAD are variable, even within families. Onset can range from childhood to late in life. Aortic dilatation typically appears first, although dissection can occur with minimal or no prior dilatation in some individuals.

Aortic aneurysms are often asymptomatic. However, depending on size, growth rate, and location, they can cause pain in the jaw, neck, chest, or back; swelling in the arms, neck, or head; difficulty swallowing or painful swallowing; hoarseness; shortness of breath; wheezing; a chronic cough; or coughing up blood. Aortic dissections typically cause sudden, severe chest or back pain, and may also lead to unusually pale skin (pallor), a weak pulse, numbness or tingling (paresthesias) in limbs, or paralysis.

Familial TAAD can occur without other associated symptoms. However, some affected individuals exhibit mild features of related conditions like Marfan syndrome or Loeys-Dietz syndrome. These include tall stature, stretch marks, excessive joint flexibility (joint hypermobility), and a sunken or protruding chest. Occasionally, aneurysms develop in the brain or abdominal aorta. Some individuals have congenital heart defects. Other possible, but common, findings include inguinal hernias, scoliosis (spinal curvature), or livedo reticularis (purplish skin discoloration due to dermal capillary abnormalities). Depending on the specific genetic cause of familial TAAD in a given family, there may be an increased risk of arterial blockages, potentially leading to heart attack or stroke.

Inheritance:

Familial TAAD is typically inherited in an autosomal dominant manner. This means that only one copy of a mutated gene in each cell is sufficient to cause the disorder. Usually, an affected individual has one affected parent. However, some people with the mutated gene may not develop aortic abnormalities, a phenomenon known as reduced penetrance.