Aneurysm and aortic dissection family (Familial thoracic aortic aneurysm and dissection -TAAD-) - Genes ACTA2 and TGFBR2.
The aneurysm and aortic dissection family (family TAAD) is a disorder that affects the thoracic aorta, although they may also be affected other arteries.
In family TAAD, dilation of the aorta, which may cause an aneurysm or an aortic dissection can occur, allowing blood to flow between the layers abnormally. These aortic abnormalities are life - threatening because they may decrease blood flow to other parts of the body like the brain or other vital organs, or may trigger the rupture of the aorta. The appearance of these aortic abnormalities vary even within the same family affected. This alteration may begin in childhood or later occur throughout life. Aortic dilatation is generally the first characteristic that develops family TAAD, although in some affected individuals dissection occurs with little or no aortic dilatation.
Aortic aneurysms usually have no symptoms. However, depending on the size, the rate of evolution and location of changes, can cause pain in the jaw, neck, chest or back; swelling in the arms, neck or head; difficult or painful swallowing; hoarseness; difficulty breathing; wheezing; chronic cough; or coughing up blood. Meanwhile, aortic dissections usually cause severe pain in the chest or back and can also result in pale, weak pulse, paresthesias in one or more limbs, or paralysis.
This disease not usually associated with other signs and symptoms. However, some individuals show mild features of Marfan syndrome or Loeys-Dietz syndrome. These features include tall, skin striae, hypermobility and sunk or prominent thorax. Occasionally, people with familial TAAD develop aneurysms in the brain or abdominal aorta. In addition, some affected people have congenital heart defects. Affected individuals may also have inguinal hernia, scoliosis and livedo reticularis due to abnormalities in dermal capillaries. Depending on the genetic cause of familial TAAD, affected individuals may have an increased risk of developing blockages in smaller arteries, which can lead to a heart attack or stroke.
This process is because between 14% and 20% of those affected by mutations in the gene ACTA2 and 2.5% of the cases by mutations in the TGFBR2 gene. Mutations in other genes occur in lower percentages of cases.
The ACTA2 gene, located on the long arm of chromosome 10 (10q23.3), encodes a protein called ?-smooth muscle actin 2 located in vascular smooth muscle cells. The layers of these cells in the walls of the aorta and other arteries. Within the vascular smooth muscle, ?-actin 2 smooth muscle forms the core of the sarcomere contributes to the capacity of these muscles to contract, allowing the arteries maintain their shape rather than stretching when blood is pumped through them. They described more than 30 mutations in the gene in individuals ACTA2 aneurysmal aortic dissection and family. ACTA2 gene mutations change amino acids in protein ?-smooth muscle actin 2. These changes are likely to affect the way in which the protein contracts smooth muscle, which interferes with the ability of the sarcomeres to prevent arteries stretch. The aorta, where the force of blood pumped straight from the heart is more intense, is particularly vulnerable to this stretch. The stretching causes abnormal aortic dilatation, aneurysms and dissections which characterize TAAD family.
The TGFBR2 gene, located on the short arm of chromosome 3 (3p22), encodes a protein called receptor type 2 transforming growth factor beta (TGF-?). This receiver transmits signals from the cell surface into the cell through a process called signal transduction. Through this type of signaling, the environment outside the cell affects the activities within the cell such as cell growth and proliferation, differentiation, motility and apoptosis. Because the type 2 receptor of TGF-? prevents cells grow and divide too fast or in an uncontrolled manner, it is also important in suppressing tumor formation. They have been identified at least 9 TGFBR2 gene mutations in people with family aneurysm and aortic dissection. These genetic changes alter the receptor structure affecting signal transduction, which may affect cell growth and development. However, it is unclear how these changes result in specific abnormalities of the aorta associated with familial TAAD.
This disease is inherited as an autosomal dominant, which means that a copy of an altered gene in each cell may be sufficient to express the disease. In most cases, an affected person has an affected parent. However, some people who inherit an altered gene never develop associated aortic abnormalities, what is known as reduced penetrance.
Tests in IVAMI: in IVAMI perform detection of mutations associated with aneurysm and familial aortic dissection by complete PCR amplification of the exons of ACTA2 and TGFBR2, respectively, and subsequent sequencing genes.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).