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, Loeys-Dietz syndrome, or vascular Ehlers-Danlos syndrome, 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
Marfan syndrome, Loeys-Dietz syndrome, and Ehlers-Danlos syndrome are described in H00653, H00800, and H00802, respectively. [DS:H00653] [DS:H00800] [DS:H00802]
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.
Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare congenital anomaly with decreased muscular tone in the urinary tract and intestine. MMIHS is characterized by prenatal-onset distended urinary bladder with functional intestinal obstruction. Hypoperistalsis causes a pseudo-obstruction which leads to a shortened and malrotated microcolon and food intolerance. MMIHS usually affects women, and is almost lethal in the first year of life. Although pro-kinetic agents and alimentation have prolonged life in some cases, but the long term outcome remains poor. Extensive surgical intervention is required for survival. Pathogenesis of MMIHS remains unclear but impaired peristalsis seems to be owing to abnormal ganglion cells pattern and absence of interstitial Cajal cells. While it is believed to be an autosomal recessive disorder, most cases are sporadic. It has been identified de novo ACTG2 mutations cause MMIHS.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD2F Syndromes with multiple structural anomalies, without predominant body system involvement
H01869 Megacystis microcolon intestinal hypoperistalsis syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06528 Calcium signaling
H01869 Megacystis microcolon intestinal hypoperistalsis syndrome
Cellular process
nt06539 Cytoskeleton in muscle cells
H01869 Megacystis microcolon intestinal hypoperistalsis syndrome
Halim D, Wilson MP, Oliver D, Brosens E, Verheij JB, Han Y, Nanda V, Lyu Q, Doukas M, Stoop H, Brouwer RW, van IJcken WF, Slivano OJ, Burns AJ, Christie CK, de Mesy Bentley KL, Brooks AS, Tibboel D, Xu S, Jin ZG, Djuwantono T, Yan W, Alves MM, Hofstra RM, Miano JM
Title
Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice.
Visceral myopathy (VSCM) is a rare inherited form of myopathic pseudo-obstruction. It is characterized by impaired functions of enteric smooth muscle cells, resulting in abnormal intestinal motility, severe abdominal pain, malnutrition, and even death. VSCM is most commonly caused by mutations in contractile apparatus cytoskeletal proteins.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
13 Diseases of the digestive system
Diseases of small intestine
DA90 Nonstructural developmental anomalies of small intestine
H02553 Visceral myopathy
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H02553 Visceral myopathy
