Familial thoracic aortic aneurysm and dissection [DS:H00801]
Description
Loeys-Dietz syndrome (LDS) is an autosomal dominant disorder characterized by arterial aneurysms and dissections, pectus excavatum, craniosynostosis, cleft palate, congenital heart disease, and thin, translucent skin. LDS results from mutations in the TGF beta receptor genes. LDS has been subdivided in LDS1 and LDS2 on the basis of the presence or the absence of craniofacial involvement, respectively. LDS3 is associated with early-onset osteoarthritis and caused by mutation in the SMAD3 gene. LDS4 and LDS5 are caused by mutation in the TGFB2 and TGFB3 gene, respectively.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD28 Syndromes with connective tissue involvement as a major feature
H00800 Loeys-Dietz syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06507 TGFB signaling
H00800 Loeys-Dietz syndrome
Rienhoff HY Jr, Yeo CY, Morissette R, Khrebtukova I, Melnick J, Luo S, Leng N, Kim YJ, Schroth G, Westwick J, Vogel H, McDonnell N, Hall JG, Whitman M
Title
A mutation in TGFB3 associated with a syndrome of low muscle mass, growth retardation, distal arthrogryposis and clinical features overlapping with Marfan and Loeys-Dietz syndrome.
Cannaerts E, Kempers M, Maugeri A, Marcelis C, Gardeitchik T, Richer J, Micha D, Beauchesne L, Timmermans J, Vermeersch P, Meyten N, Chenier S, van de Beek G, Peeters N, Alaerts M, Schepers D, Van Laer L, Verstraeten A, Loeys B
Title
Novel pathogenic SMAD2 variants in five families with arterial aneurysm and dissection: further delineation of the phenotype.
Thoracic aortic aneurysms leading to acute aortic dissections (TAAD) are the major diseases that affect the thoracic aorta. While majority of the cases are sporadic, more than 20% are inherited as a single gene disorder. Familial TAAD is diagnosed based on the presence of dilatation and/or dissection of the thoracic aorta, absence of clinical features of Marfan syndrome [DS:H00653], Loeys-Dietz syndrome [DS:H00800], or vascular Ehlers-Danlos syndrome [DS:H00802], and presence of a positive family history of TAAD. TGFBR2, TGFBR1, MYH11, ACTA2, and two loci on other chromosomes, AAT1 and AAT2, are associated with familial TAAD.
Category
Cardiovascular disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
11 Diseases of the circulatory system
Diseases of arteries or arterioles
BD50 Aortic aneurysm or dissection
H00801 Familial thoracic aortic aneurysm and dissection
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06507 TGFB signaling
H00801 Familial thoracic aortic aneurysm and dissection
nt06528 Calcium signaling
H00801 Familial thoracic aortic aneurysm and dissection
Cellular process
nt06539 Cytoskeleton in muscle cells
H00801 Familial thoracic aortic aneurysm and dissection
Endocrine system
nt06325 Hormone/cytokine signaling
H00801 Familial thoracic aortic aneurysm and dissection
Guo DC, Regalado ES, Minn C, Tran-Fadulu V, Coney J, Cao J, Wang M, Yu RK, Estrera AL, Safi HJ, Shete SS, Milewicz DM
Title
Familial thoracic aortic aneurysms and dissections: identification of a novel locus for stable aneurysms with a low risk for progression to aortic dissection.
Erbel R, Alfonso F, Boileau C, Dirsch O, Eber B, Haverich A, Rakowski H, Struyven J, Radegran K, Sechtem U, Taylor J, Zollikofer C, Klein WW, Mulder B, Providencia LA
Zhu L, Vranckx R, Khau Van Kien P, Lalande A, Boisset N, Mathieu F, Wegman M, Glancy L, Gasc JM, Brunotte F, Bruneval P, Wolf JE, Michel JB, Jeunemaitre X
Title
Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus.
Barbier M, Gross MS, Aubart M, Hanna N, Kessler K, Guo DC, Tosolini L, Ho-Tin-Noe B, Regalado E, Varret M, Abifadel M, Milleron O, Odent S, Dupuis-Girod S, Faivre L, Edouard T, Dulac Y, Busa T, Gouya L, Milewicz DM, Jondeau G, Boileau C
Title
MFAP5 loss-of-function mutations underscore the involvement of matrix alteration in the pathogenesis of familial thoracic aortic aneurysms and dissections.
Elbitar S, Renard M, Arnaud P, Hanna N, Jacob MP, Guo DC, Tsutsui K, Gross MS, Kessler K, Tosolini L, Dattilo V, Dupont S, Jonquet J, Langeois M, Benarroch L, Aubart M, Ghaleb Y, Abou Khalil Y, Varret M, El Khoury P, Ho-Tin-Noe B, Alembik Y, Gaertner S, Isidor B, Gouya L, Milleron O, Sekiguchi K, Milewicz D, De Backer J, Le Goff C, Michel JB, Jondeau G, Sakai LY, Boileau C, Abifadel M
Title
Pathogenic variants in THSD4, encoding the ADAMTS-like 6 protein, predispose to inherited thoracic aortic aneurysm.
