Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Familial Thoracic Aortic Aneurysm and Dissection (TAAD) [I71.1] [I71.2]

Aortendissektion, familiär thorakaler Typ 3-Typ 7 (AAT3-AAT7)
Aneurysmen Osteoarthritis Syndrom (AOS)
Loeys-Dietz-Syndrom Typ 4 (LDS4) [I71.1] [I71.2]

OMIM numbers: 609192, 190182 (TGFBR2), 132900, 160745 (MYH11), 609192, 190181 (TGFBR1), 611788, 102620 (ACTA2), 613780, 600922 (MYLK), 613795, 603109 (SMAD3), 614816, 190220 (TGFB2)

Dr. rer. nat. Karin Mayer

Scientific Background

Thoracic aneurysms of the aorta ascendens with type A dissection (shortly after the aortic valve) (TAAD) may occur as an isolated abnormality or due to genetic syndromes. Hereditary connective tissue disorders that are associated with a high risk for TAAD are the classic Marfan syndrome (MFS), the Loeys-Dietz syndrome (LDS) and the vascular type of the Ehlers-Danlos syndrome (EDS type IV). About 10–20% of the isolated forms of TAAD are inherited in an autosomal dominant pattern with reduced penetrance and variable expression. TAAD are clinically as well as genetically heterogeneous.

So far, nine gene loci for familial TAAD have been localized by coupling analysis and seven genes have been identified: AAT1 on chromosome 11q23–24, AAT2 on chromosome 5q13–14, AAT3 on chromosome 3p24–25 (TGFBR2 gene), AAT4 on chromosome 16p13.13–p13.12 (MYH11 gene), AAT5 on chromosome 9q33–q34 (TGFBR1 gene), AAT6 on chromosome 10q22–24 (ACTA2 gene) and AAT7 on chromosome 3q21 (MYLK gene). For AAT1 and AAT2 no gene has been identified yet. In 2011 an eighth gene loci for TAAD was identified on chromosome 15q22.2–24.2 (SMAD3 gene) and in 2012 an additional gene was identified on chromosome 1q41 (TGFB2 gene).

Thus far the classification in AAT1–AAT7 was made chronologically by reference to the mapped gene loci and represents the current state of research. With the identification of further genes this classification becomes more and more obsolete.