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Aortic aneurysm, familial thoracic 4(AAT4)

MedGen UID:
338704
Concept ID:
C1851504
Disease or Syndrome
Synonyms: AAT4; Aortic aneurysm/aortic dissection and patent ductus arteriosus; MYH11-Related Thoracic Aortic Aneurysms and Aortic Dissections
 
Gene (location): MYH11 (16p13.11)
 
Monarch Initiative: MONDO:0007568
OMIM®: 132900

Definition

Familial TAAD may not be associated with other signs and symptoms. However, some individuals in affected families show mild features of related conditions called Marfan syndrome or Loeys-Dietz syndrome. These features include tall stature, stretch marks on the skin, an unusually large range of joint movement (joint hypermobility), and either a sunken or protruding chest. Occasionally, people with familial TAAD develop aneurysms in the brain or in the section of the aorta located in the abdomen (abdominal aorta). Some people with familial TAAD have heart abnormalities that are present from birth (congenital). Affected individuals may also have a soft out-pouching in the lower abdomen (inguinal hernia), an abnormal curvature of the spine (scoliosis), or a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin (dermal capillaries). However, these conditions are also common in the general population. Depending on the genetic cause of familial TAAD in particular families, they may have an increased risk of developing blockages in smaller arteries, which can lead to heart attack and stroke.

The occurrence and timing of these aortic abnormalities vary, even within the same affected family. They can begin in childhood or not occur until late in life. Aortic dilatation is generally the first feature of familial TAAD to develop, although in some affected individuals dissection occurs with little or no aortic dilatation.

In familial TAAD, the aorta can become weakened and stretched (aortic dilatation), which can lead to a bulge in the blood vessel wall (an aneurysm). Aortic dilatation may also lead to a sudden tearing of the layers in the aorta wall (aortic dissection), allowing blood to flow abnormally between the layers. These aortic abnormalities are potentially life-threatening because they can decrease blood flow to other parts of the body such as the brain or other vital organs, or cause the aorta to break open (rupture).

Familial thoracic aortic aneurysm and dissection (familial TAAD) involves problems with the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. Familial TAAD affects the upper part of the aorta, near the heart. This part of the aorta is called the thoracic aorta because it is located in the chest (thorax). Other vessels that carry blood from the heart to the rest of the body (arteries) can also be affected.

Aortic aneurysms usually have no symptoms. However, depending on the size, growth rate, and location of these abnormalities, they can cause pain in the jaw, neck, chest, or back; swelling in the arms, neck, or head; difficult or painful swallowing; hoarseness; shortness of breath; wheezing; a chronic cough; or coughing up blood. Aortic dissections usually cause severe, sudden chest or back pain, and may also result in unusually pale skin (pallor), a very faint pulse, numbness or tingling (paresthesias) in one or more limbs, or paralysis. [from MedlinePlus Genetics]

Clinical features

From HPO
Aortic regurgitation
MedGen UID:
8153
Concept ID:
C0003504
Disease or Syndrome
An insufficiency of the aortic valve, leading to regurgitation (backward flow) of blood from the aorta into the left ventricle.
Carotid artery stenosis
MedGen UID:
785
Concept ID:
C0007282
Disease or Syndrome
Narrowing of the carotid arteries.
Coronary artery atherosclerosis
MedGen UID:
3623
Concept ID:
C0010054
Disease or Syndrome
Reduction of the diameter of the coronary arteries as the result of an accumulation of atheromatous plaques within the walls of the coronary arteries, which increases the risk of myocardial ischemia.
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Stroke
MedGen UID:
52522
Concept ID:
C0038454
Disease or Syndrome
Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain.
Bicuspid aortic valve
MedGen UID:
57436
Concept ID:
C0149630
Congenital Abnormality
Bicuspid, or bicommissural, aortic valve (BAV) describes an aortic valve with 2 rather than 3 leaflets (Cripe et al., 2004). In 1 to 2% of the population a bicuspid aortic valve is present. Bicuspid aortic valve is frequently an antecedent to aortic valve stenosis or insufficiency. In extreme cases the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome (241550) (Garg et al., 2005). The valve calcification often observed in bicuspid aortic valve is a result of inappropriate activation of osteoblast-specific gene expression. Mutations in the signaling and transcription regulator NOTCH1 cause a spectrum of developmental aortic valve anomalies and severe valve calcification in nonsyndromic autosomal dominant human pedigrees. Genetic Heterogeneity of Aortic Valve Disease Also see AOVD2 (614823), caused by mutation in the SMAD6 gene (602931) on chromosome 15q22, and AOVD3 (618496), caused by mutation in the ROBO4 gene (607528) on chromosome 11q24. There is evidence for additional genetic heterogeneity (see MAPPING).
Thoracic aortic aneurysm
MedGen UID:
56525
Concept ID:
C0162872
Anatomical Abnormality
An abnormal localized widening (dilatation) of the thoracic aorta.
Abnormal left ventricular function
MedGen UID:
69237
Concept ID:
C0242698
Pathologic Function
Inability of the left ventricle to perform its normal physiologic function. Failure is either due to an inability to contract the left ventricle or the inability to relax completely and fill with blood during diastole.
Aortic dissection
MedGen UID:
83315
Concept ID:
C0340643
Disease or Syndrome
Aortic dissection refers to a tear in the intimal layer of the aorta causing a separation between the intima and the medial layers of the aorta.
Ascending tubular aorta aneurysm
MedGen UID:
163631
Concept ID:
C0856747
Anatomical Abnormality
An abnormal localized widening (dilatation) of the tubular part of the ascending aorta.
Anterior cerebral artery stenosis
MedGen UID:
760199
Concept ID:
C1504567
Disease or Syndrome
Narrowing or constriction of the inner surface (lumen) of the anterior cerebral artery.
Middle cerebral artery stenosis
MedGen UID:
760200
Concept ID:
C1504568
Disease or Syndrome
Narrowing or constriction of the inner surface (lumen) of the middle cerebral artery.
Posterior cerebral artery stenosis
MedGen UID:
760201
Concept ID:
C1504569
Disease or Syndrome
Narrowing or constriction of the inner surface (lumen) of the posterior cerebral artery.
Ascending aortic dissection
MedGen UID:
322966
Concept ID:
C1836653
Disease or Syndrome
A separation of the layers within the wall of the ascending aorta. Tears in the intimal layer result in the propagation of dissection (proximally or distally) secondary to blood entering the intima-media space.
Descending aortic dissection
MedGen UID:
868484
Concept ID:
C4022878
Disease or Syndrome
A separation of the layers within the wall of the descending aorta. Tears in the intimal layer result in the propagation of dissection (proximally or distally) secondary to blood entering the intima-media space.
Cystic medial necrosis
MedGen UID:
1638446
Concept ID:
C4551473
Disease or Syndrome
A disorder of large arteries, in particular the aorta, characterized by an accumulation of basophilic ground substance in the media with cyst-like lesions associated with degenerative changes of collagen, elastin and the vascular smooth muscle cells.
Livedo reticularis
MedGen UID:
43223
Concept ID:
C0085642
Disease or Syndrome
Livedo reticularis is characterized by the presence of a bluish purple, mottled or netlike pattern in unbroken circles on the skin. Exposure to cold environments usually intensifies the vascular pattern. Presumably, the condition results from slow or stagnant blood flow, vessel-wall pathology, and decreased oxygen tension.
Abnormal iris pigmentation
MedGen UID:
331733
Concept ID:
C1834387
Finding
Abnormal pigmentation of the iris.

Recent clinical studies

Etiology

Núñez-Gil IJ, Bautista D, Cerrato E, Salinas P, Varbella F, Omedè P, Ugo F, Ielasi A, Giammaria M, Moreno R, Pérez-Vizcayno MJ, Escaned J, De Agustin JA, Feltes G, Macaya C, Fernández-Ortiz A; Registry on Aortic Iatrogenic Dissection (RAID) Investigators
Circulation 2015 Jun 16;131(24):2114-9. Epub 2015 Apr 17 doi: 10.1161/CIRCULATIONAHA.115.015334. PMID: 25888682

Diagnosis

Núñez-Gil IJ, Bautista D, Cerrato E, Salinas P, Varbella F, Omedè P, Ugo F, Ielasi A, Giammaria M, Moreno R, Pérez-Vizcayno MJ, Escaned J, De Agustin JA, Feltes G, Macaya C, Fernández-Ortiz A; Registry on Aortic Iatrogenic Dissection (RAID) Investigators
Circulation 2015 Jun 16;131(24):2114-9. Epub 2015 Apr 17 doi: 10.1161/CIRCULATIONAHA.115.015334. PMID: 25888682

Therapy

Núñez-Gil IJ, Bautista D, Cerrato E, Salinas P, Varbella F, Omedè P, Ugo F, Ielasi A, Giammaria M, Moreno R, Pérez-Vizcayno MJ, Escaned J, De Agustin JA, Feltes G, Macaya C, Fernández-Ortiz A; Registry on Aortic Iatrogenic Dissection (RAID) Investigators
Circulation 2015 Jun 16;131(24):2114-9. Epub 2015 Apr 17 doi: 10.1161/CIRCULATIONAHA.115.015334. PMID: 25888682

Prognosis

Núñez-Gil IJ, Bautista D, Cerrato E, Salinas P, Varbella F, Omedè P, Ugo F, Ielasi A, Giammaria M, Moreno R, Pérez-Vizcayno MJ, Escaned J, De Agustin JA, Feltes G, Macaya C, Fernández-Ortiz A; Registry on Aortic Iatrogenic Dissection (RAID) Investigators
Circulation 2015 Jun 16;131(24):2114-9. Epub 2015 Apr 17 doi: 10.1161/CIRCULATIONAHA.115.015334. PMID: 25888682

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