Skip to main content
SpringerLink
Log in

Loeys-Dietz Syndrome

  • Chapter
  • First Online:
Progress in Heritable Soft Connective Tissue Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1348))

Abstract

Loeys-Dietz syndrome is an autosomal dominant aortic aneurysm syndrome characterized by multisystemic involvement. The most typical clinical triad includes hypertelorism, bifid uvula or cleft palate and aortic aneurysm with tortuosity. Natural history is significant for aortic dissection at smaller aortic diameter and arterial aneurysms throughout the arterial tree. The genetic cause is heterogeneous and includes mutations in genes encoding for components of the transforming growth factor beta (TGFβ) signalling pathway: TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2 and TGFB3. Despite the loss of function nature of these mutations, the patient-derived aortic tissues show evidence of increased (rather than decreased) TGFβ signalling. These insights offer new options for therapeutic interventions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AOS:

Aneurysm-osteoarthritis syndrome

ARCL1:

Autosomal recessive cutis laxa type 1

ASD/VSD:

Atrial and ventricular septum defects

ATS:

Arterial tortuosity syndrome

BAV:

Bicuspid aortic valve

BMP:

Bone morphogenetic protein

EDS:

Ehlers-Danlos syndrome

LDS:

Loeys-Dietz syndrome

MFS:

Marfan syndrome

PDA:

Patent ductus arteriosus

PLOD1:

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1

SGS:

Shprintzen-Goldberg syndrome

TAAD:

Thoracic aortic aneurysms and dissections

TGFβ:

Transforming growth factor β

TGFβR :

Transforming growth factor β receptor

References

  • Al-Abcha A, Saleh Y, Mujer M, Boumegouas M, Herzallah K, Charles L, Elkhatib L, Abdelkarim O, Kehdi M, Abela GS (2020) Meta-analysis examining the usefulness of angiotensin receptor blockers for the prevention of aortic root dilation in patients with the Marfan syndrome. Am J Cardiol 128:101–106

    Article  CAS  PubMed  Google Scholar 

  • Augoustides JG, Plappert T, Bavaria JE (2009) Aortic decision-making in the Loeys-Dietz syndrome: aortic root aneurysm and a normal-caliber ascending aorta and aortic arch. J Thorac Cardiovasc Surg 138:502–503

    Article  PubMed  Google Scholar 

  • Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ (1998) Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos support group (UK). Am J Med Genet 77:31–37

    Article  CAS  PubMed  Google Scholar 

  • Bertoli-Avella AM, Gillis E, Morisaki H, Verhagen JMA, de Graaf BM, van de Beek G, Gallo E, Kruithof BPT, Venselaar H, Myers LA, Laga S, Doyle AJ, Oswald G, van Cappellen GWA, Yamanaka I, van der Helm RM, Beverloo B, de Klein A, Pardo L, Lammens M, Evers C, Devriendt K, Dumoulein M, Timmermans J, Bruggenwirth HT, Verheijen F, Rodrigus I, Baynam G, Kempers M, Saenen J, Van Craenenbroeck EM, Minatoya K, Matsukawa R, Tsukube T, Kubo N, Hofstra R, Goumans MJ, Bekkers JA, Roos-Hesselink JW, van de Laar I, Dietz HC, Van Laer L, Morisaki T, Wessels MW, Loeys BL (2015) Mutations in a TGF-beta ligand, TGFB3, cause syndromic aortic aneurysms and dissections. J Am Coll Cardiol 65:1324–1336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brooke BS, Habashi JP, Judge DP, Patel N, Loeys B, Dietz HC 3rd. (2008) Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. N Engl J Med 358:2787–2795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campbell IM, Kolodziejska KE, Quach MM, Wolf VL, Cheung SW, Lalani SR, Ramocki MB, Stankiewicz P (2011) TGFBR2 deletion in a 20-month-old female with developmental delay and microcephaly. Am J Med Genet A 155A:1442–1447

    Article  PubMed  Google Scholar 

  • 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 (2019) Novel pathogenic SMAD2 variants in five families with arterial aneurysm and dissection: further delineation of the phenotype. J Med Genet 56:220–227

    Article  CAS  PubMed  Google Scholar 

  • Cardoso S, Robertson SP, Daniel PB (2012) TGFBR1 mutations associated with Loeys-Dietz syndrome are inactivating. J Recept Signal Transduct Res 32:150–155

    Article  CAS  PubMed  Google Scholar 

  • Coucke PJ, Willaert A, Wessels MW, Callewaert B, Zoppi N, De Backer J, Fox JE, Mancini GM, Kambouris M, Gardella R, Facchetti F, Willems PJ, Forsyth R, Dietz HC, Barlati S, Colombi M, Loeys B, De Paepe A (2006) Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet 38:452–457

    Article  CAS  PubMed  Google Scholar 

  • Detaint D, Aegerter P, Tubach F, Hoffman I, Plauchu H, Dulac Y, Faivre LO, Delrue MA, Collignon P, Odent S, Tchitchinadze M, Bouffard C, Arnoult F, Gautier M, Boileau C, Jondeau G (2010) Rationale and design of a randomized clinical trial (Marfan Sartan) of angiotensin II receptor blocker therapy versus placebo in individuals with Marfan syndrome. Arch Cardiovasc Dis 103:317–325

    Article  PubMed  Google Scholar 

  • Doyle AJ, Doyle JJ, Bessling SL, Maragh S, Lindsay ME, Schepers D, Gillis E, Mortier G, Homfray T, Sauls K, Norris RA, Huso ND, Leahy D, Mohr DW, Caulfield MJ, Scott AF, Destree A, Hennekam RC, Arn PH, Curry CJ, Van Laer L, McCallion AS, Loeys BL, Dietz HC (2012) Mutations in the TGF-beta repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm. Nat Genet

    Google Scholar 

  • Eckman PM, Hsich E, Rodriguez ER, Gonzalez-Stawinski GV, Moran R, Taylor DO (2009) Impaired systolic function in Loeys-Dietz syndrome: a novel cardiomyopathy? Circ Heart Fail 2:707–708

    Article  PubMed  Google Scholar 

  • Elbadawi A, Omer MA, Elgendy IY, Abuzaid A, Mohamed AH, Rai D, Saad M, Mentias A, Rezq A, Kamal D, Khalife W, London B, Morsy M (2019) Losartan for preventing aortic root dilatation in patients with Marfan syndrome: a meta-analysis of randomized trials. Cardiol Ther 8:365–372

    Article  PubMed  PubMed Central  Google Scholar 

  • Gambarin FI, Favalli V, Serio A, Regazzi M, Pasotti M, Klersy C, Dore R, Mannarino S, Vigano M, Odero A, Amato S, Tavazzi L, Arbustini E (2009) Rationale and design of a trial evaluating the effects of losartan vs. nebivolol vs. the association of both on the progression of aortic root dilation in Marfan syndrome with FBN1 gene mutations. J Cardiovasc Med (Hagerstown) 10:354–362

    Article  Google Scholar 

  • Goudie DR, D'Alessandro M, Merriman B, Lee H, Szeverenyi I, Avery S, O'Connor BD, Nelson SF, Coats SE, Stewart A, Christie L, Pichert G, Friedel J, Hayes I, Burrows N, Whittaker S, Gerdes AM, Broesby-Olsen S, Ferguson-Smith MA, Verma C, Lunny DP, Reversade B, Lane EB (2011) Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1. Nat Genet 43:365–369

    Article  CAS  PubMed  Google Scholar 

  • Guo DC, Pannu H, Tran-Fadulu V, Papke CL, Yu RK, Avidan N, Bourgeois S, Estrera AL, Safi HJ, Sparks E, Amor D, Ades L, McConnell V, Willoughby CE, Abuelo D, Willing M, Lewis RA, Kim DH, Scherer S, Tung PP, Ahn C, Buja LM, Raman CS, Shete SS, Milewicz DM (2007) Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet 39:1488–1493

    Article  CAS  PubMed  Google Scholar 

  • Guo DC, Papke CL, Tran-Fadulu V, Regalado ES, Avidan N, Johnson RJ, Kim DH, Pannu H, Willing MC, Sparks E, Pyeritz RE, Singh MN, Dalman RL, Grotta JC, Marian AJ, Boerwinkle EA, Frazier LQ, LeMaire SA, Coselli JS, Estrera AL, Safi HJ, Veeraraghavan S, Muzny DM, Wheeler DA, Willerson JT, Yu RK, Shete SS, Scherer SE, Raman CS, Buja LM, Milewicz DM (2009) Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease. Am J Hum Genet 84:617–627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo DC, Regalado E, Casteel DE, Santos-Cortez RL, Gong L, Kim JJ, Dyack S, Horne SG, Chang G, Jondeau G, Boileau C, Coselli JS, Li Z, Leal SM, Shendure J, Rieder MJ, Bamshad MJ, Nickerson DA, Gen TACRC, National Heart L, Blood Institute Grand Opportunity Exome Sequencing, P, Kim C, Milewicz DM (2013) Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections. Am J Hum Genet 93:398–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gutman G, Baris HN, Hirsch R, Mandel D, Yaron Y, Lessing JB, Kuperminc MJ (2009) Loeys-Dietz syndrome in pregnancy: a case description and report of a novel mutation. Fetal Diagn Ther 26:35–37

    Article  PubMed  Google Scholar 

  • Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC (2006) Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312:117–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Holm TM, Habashi JP, Doyle JJ, Bedja D, Chen Y, van Erp C, Lindsay ME, Kim D, Schoenhoff F, Cohn RD, Loeys BL, Thomas CJ, Patnaik S, Marugan JJ, Judge DP, Dietz HC (2011) Noncanonical TGFbeta signaling contributes to aortic aneurysm progression in Marfan syndrome mice. Science (New York, NY) 332:358–361

    Article  CAS  Google Scholar 

  • Horbelt D, Guo G, Robinson PN, Knaus P (2010) Quantitative analysis of TGFBR2 mutations in Marfan-syndrome-related disorders suggests a correlation between phenotypic severity and Smad signaling activity. J Cell Sci 123:4340–4350

    Article  CAS  PubMed  Google Scholar 

  • Huang T, David L, Mendoza V, Yang Y, Villarreal M, De K, Sun L, Fang X, Lopez-Casillas F, Wrana JL, Hinck AP (2011) TGF-beta signalling is mediated by two autonomously functioning TbetaRI:TbetaRII pairs. EMBO J 30:1263–1276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hucthagowder V, Sausgruber N, Kim KH, Angle B, Marmorstein LY, Urban Z (2006) Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome. Am J Hum Genet 78:1075–1080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirmani S, Tebben PJ, Lteif AN, Gordon D, Clarke BL, Hefferan TE, Yaszemski MJ, McGrann PS, Lindor NM, Ellison JW (2010) Germline TGF-beta receptor mutations and skeletal fragility: a report on two patients with Loeys-Dietz syndrome. Am J Med Genet A 152A:1016–1019

    Article  PubMed  Google Scholar 

  • Kuang SQ, Medina-Martinez O, Guo DC, Gong L, Regalado ES, Reynolds CL, Boileau C, Jondeau G, Prakash SK, Kwartler CS, Zhu LY, Peters AM, Duan XY, Bamshad MJ, Shendure J, Nickerson DA, Santos-Cortez RL, Dong X, Leal SM, Majesky MW, Swindell EC, Jamrich M, Milewicz DM (2016) FOXE3 mutations predispose to thoracic aortic aneurysms and dissections. J Clin Invest 126:948–961

    Article  PubMed  PubMed Central  Google Scholar 

  • Lacro RV, Dietz HC, Wruck LM, Bradley TJ, Colan SD, Devereux RB, Klein GL, Li JS, Minich LL, Paridon SM, Pearson GD, Printz BF, Pyeritz RE, Radojewski E, Roman MJ, Saul JP, Stylianou MP, Mahony L (2007) Rationale and design of a randomized clinical trial of beta-blocker therapy (atenolol) versus angiotensin II receptor blocker therapy (losartan) in individuals with Marfan syndrome. Am Heart J 154:624–631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lindsay ME, Dietz HC (2011) Lessons on the pathogenesis of aneurysm from heritable conditions. Nature 473:308–316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lindsay ME, Schepers D, Bolar NA, Doyle JJ, Gallo E, Fert-Bober J, Kempers MJ, Fishman EK, Chen Y, Myers L, Bjeda D, Oswald G, Elias AF, Levy HP, Anderlid BM, Yang MH, Bongers EM, Timmermans J, Braverman AC, Canham N, Mortier GR, Brunner HG, Byers PH, Van Eyk J, Van Laer L, Dietz HC, Loeys BL (2012) Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. Nat Genet 44:922–927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loeys B, Van Maldergem L, Mortier G, Coucke P, Gerniers S, Naeyaert JM, De Paepe A (2002) Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa. Hum Mol Genet 11:2113–2118

    Article  CAS  PubMed  Google Scholar 

  • Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, Xu FL, Myers LA, Spevak PJ, Cameron DE, De Backer J, Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, De Paepe AM, Dietz HC (2005) A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet 37:275–281

    Article  CAS  PubMed  Google Scholar 

  • Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, De Backer JF, Oswald GL, Symoens S, Manouvrier S, Roberts AE, Faravelli F, Greco MA, Pyeritz RE, Milewicz DM, Coucke PJ, Cameron DE, Braverman AC, Byers PH, De Paepe AM, Dietz HC (2006) Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med 355:788–798

    Article  CAS  PubMed  Google Scholar 

  • Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, Hilhorst-Hofstee Y, Jondeau G, Faivre L, Milewicz DM, Pyeritz RE, Sponseller PD, Wordsworth P, De Paepe AM (2010) The revised Ghent nosology for the Marfan syndrome. J Med Genet 47:476–485

    Article  CAS  PubMed  Google Scholar 

  • Malfait F, Symoens S, De Backer J, Hermanns-Le T, Sakalihasan N, Lapiere CM, Coucke P, De Paepe A (2007) Three arginine to cysteine substitutions in the pro-alpha (I)-collagen chain cause Ehlers-Danlos syndrome with a propensity to arterial rupture in early adulthood. Hum Mutat 28:387–395

    Article  CAS  PubMed  Google Scholar 

  • Meester JA, Vandeweyer G, Pintelon I, Lammens M, Van Hoorick L, De Belder S, Waitzman K, Young L, Markham LW, Vogt J, Richer J, Beauchesne LM, Unger S, Superti-Furga A, Prsa M, Dhillon R, Reyniers E, Dietz HC, Wuyts W, Mortier G, Verstraeten A, Van Laer L, Loeys BL (2016) Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections. Genet Med

    Google Scholar 

  • Milewicz DM, Michael K, Fisher N, Coselli JS, Markello T, Biddinger A (1996) Fibrillin-1 (FBN1) mutations in patients with thoracic aortic aneurysms. Circulation 94:2708–2711

    Article  CAS  PubMed  Google Scholar 

  • Mizuguchi T, Collod-Beroud G, Akiyama T, Abifadel M, Harada N, Morisaki T, Allard D, Varret M, Claustres M, Morisaki H, Ihara M, Kinoshita A, Yoshiura K, Junien C, Kajii T, Jondeau G, Ohta T, Kishino T, Furukawa Y, Nakamura Y, Niikawa N, Boileau C, Matsumoto N (2004) Heterozygous TGFBR2 mutations in Marfan syndrome. Nat Genet 36:855–860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moberg K, De Nobele S, Devos D, Goetghebeur E, Segers P, Trachet B, Vervaet C, Renard M, Coucke P, Loeys B, De Paepe A, De Backer J (2012) The Ghent Marfan trial – a randomized, double-blind placebo controlled trial with losartan in Marfan patients treated with beta-blockers. Int J Cardiol 157:354–358

    Article  PubMed  Google Scholar 

  • Neptune ER, Frischmeyer PA, Arking DE, Myers L, Bunton TE, Gayraud B, Ramirez F, Sakai LY, Dietz HC (2003) Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat Genet 33:407–411

    Article  CAS  PubMed  Google Scholar 

  • Pannu H, Fadulu VT, Chang J, Lafont A, Hasham SN, Sparks E, Giampietro PF, Zaleski C, Estrera AL, Safi HJ, Shete S, Willing MC, Raman CS, Milewicz DM (2005) Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections. Circulation 112:513–520

    Article  CAS  PubMed  Google Scholar 

  • Patel ND, Arnaoutakis GJ, George TJ, Allen JG, Alejo DE, Dietz HC, Cameron DE, Vricella LA (2011) Valve-sparing aortic root replacement in Loeys-Dietz syndrome. Ann Thorac Surg 92:556–560. discussion 560-551

    Article  PubMed  Google Scholar 

  • Pinnell SR, Krane SM, Kenzora JE, Glimcher MJ (1972) A heritable disorder of connective tissue. Hydroxylysine-deficient collagen disease. N Engl J Med 286:1013–1020

    Article  CAS  PubMed  Google Scholar 

  • Pyeritz RE, Loeys B (2011) The 8th international research symposium on the Marfan syndrome and related conditions. Am J Med Genet A

    Google Scholar 

  • Radonic T, de Witte P, Baars MJ, Zwinderman AH, Mulder BJ, Groenink M (2010) Losartan therapy in adults with Marfan syndrome: study protocol of the multi-center randomized controlled COMPARE trial. Trials 11:3

    Article  PubMed  PubMed Central  Google Scholar 

  • Regalado ES, Guo DC, Villamizar C, Avidan N, Gilchrist D, McGillivray B, Clarke L, Bernier F, Santos-Cortez RL, Leal SM, Bertoli-Avella AM, Shendure J, Rieder MJ, Nickerson DA, Milewicz DM (2011) Exome sequencing identifies SMAD3 mutations as a cause of familial thoracic aortic aneurysm and dissection with intracranial and other arterial aneurysms. Circ Res 109:680–686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodrigues VJ, Elsayed S, Loeys BL, Dietz HC, Yousem DM (2009) Neuroradiologic manifestations of Loeys-Dietz syndrome type 1. AJNR Am J Neuroradiol 30:1614–1619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schwarze U, Hata R, McKusick VA, Shinkai H, Hoyme HE, Pyeritz RE, Byers PH (2004) Rare autosomal recessive cardiac valvular form of Ehlers-Danlos syndrome results from mutations in the COL1A2 gene that activate the nonsense-mediated RNA decay pathway. Am J Hum Genet 74:917–930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sellers SL, Milad N, Chan R, Mielnik M, Jermilova U, Huang PL, de Crom R, Hirota JA, Hogg JC, Sandor GG, Van Breemen C, Esfandiarei M, Seidman MA, Bernatchez P (2018) Inhibition of Marfan syndrome aortic root dilation by losartan: role of angiotensin II receptor type 1-independent activation of endothelial function. Am J Pathol 188:574–585

    Article  CAS  PubMed  Google Scholar 

  • Tran-Fadulu V, Pannu H, Kim DH, Vick GW 3rd, Lonsford CM, Lafont AL, Boccalandro C, Smart S, Peterson KL, Hain JZ, Willing MC, Coselli JS, LeMaire SA, Ahn C, Byers PH, Milewicz DM (2009) Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations. J Med Genet 46:607–613

    Article  CAS  PubMed  Google Scholar 

  • van de Laar IM, Oldenburg RA, Pals G, Roos-Hesselink JW, de Graaf BM, Verhagen JM, Hoedemaekers YM, Willemsen R, Severijnen LA, Venselaar H, Vriend G, Pattynama PM, Collee M, Majoor-Krakauer D, Poldermans D, Frohn-Mulder IM, Micha D, Timmermans J, Hilhorst-Hofstee Y, Bierma-Zeinstra SM, Willems PJ, Kros JM, Oei EH, Oostra BA, Wessels MW, Bertoli-Avella AM (2011) Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis. Nat Genet 43:121–126

    Article  PubMed  Google Scholar 

  • van de Laar IM, van der Linde D, Oei EH, Bos PK, Bessems JH, Bierma-Zeinstra SM, van Meer BL, Pals G, Oldenburg RA, Bekkers JA, Moelker A, de Graaf BM, Matyas G, Frohn-Mulder IM, Timmermans J, Hilhorst-Hofstee Y, Cobben JM, Bruggenwirth HT, van Laer L, Loeys B, De Backer J, Coucke PJ, Dietz HC, Willems PJ, Oostra BA, De Paepe A, Roos-Hesselink JW, Bertoli-Avella AM, Wessels MW (2012) Phenotypic spectrum of the SMAD3-related aneurysms-osteoarthritis syndrome. J Med Genet 49:47–57

    Article  PubMed  Google Scholar 

  • van der Linde D, van de Laar IMBM, Bertoli-Avella AM, Oldenburg RA, Bekkers JA, Mattace-Raso FUS, van den Meiracker AH, Moelker A, Tanghe HLJ, van Kooten F, Frohn IME, Timmermans J, Moltzer E, Cobben JM, Van Laer L, Loeys B, De Backer J, Coucke PJ, De Paepe A, Wessels MW, Roos-Hesselink JW (2012) Cardiovascular phenotype of the recently discovered aneurysms-osteoarthritis syndrome (AOS) caused by SMAD3 mutations. J Am Coll Cardiol. (In press)

    Google Scholar 

  • Wang L, Guo DC, Cao J, Gong L, Kamm KE, Regalado E, Li L, Shete S, He WQ, Zhu MS, Offermanns S, Gilchrist D, Elefteriades J, Stull JT, Milewicz DM (2010) Mutations in myosin light chain kinase cause familial aortic dissections. Am J Hum Genet 87:701–707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watanabe Y, Sakai H, Nishimura A, Miyake N, Saitsu H, Mizuguchi T, Matsumoto N (2008) Paternal somatic mosaicism of a TGFBR2 mutation transmitting to an affected son with Loeys-Dietz syndrome. Am J Med Genet A 146A:3070–3074

    Article  CAS  PubMed  Google Scholar 

  • Williams JA, Loeys BL, Nwakanma LU, Dietz HC, Spevak PJ, Patel ND, Francois K, DeBacker J, Gott VL, Vricella LA, Cameron DE (2007) Early surgical experience with Loeys-Dietz: a new syndrome of aggressive thoracic aortic aneurysm disease. Ann Thorac Surg 83:S757–S763. discussion S785-790

    Article  PubMed  Google Scholar 

  • Wischmeijer A, Van Laer L, Tortora G, Ajit Bolar N, Van Camp G, Fransen E, Peeters N, di Bartolomeo R, Pacini D, Gargiulo G, Turci S, Bonvicini M, Mariucci E, Lovato L, Brusori S, Ritelli M, Colombi M, Garavelli L, Seri M, Loeys BL (2013) First report of thoracic aortic aneurysm in infancy in a family with aneurysms-osteoarthritis syndrome due to a novel SMAD3 mutation: further delineation of the clinical phenotype. Am J Med Genet A. Minor revision

    Google Scholar 

  • 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 (2006) Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus. Nat Genet 38:343–349

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Medical Genetics, Antwerp University Hospital/University of Antwerp, Antwerp, Belgium

    Joe D. Velchev, Lut Van Laer, Ilse Luyckx & Bart Loeys

  2. Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands

    Ilse Luyckx & Bart Loeys

  3. Harry Dietz, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Harry Dietz

Authors
  1. Joe D. Velchev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lut Van Laer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ilse Luyckx
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Harry Dietz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bart Loeys
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bart Loeys .

Editor information

Editors and Affiliations

  1. Department of Pathology, College of Veterinary Medicine, and Department of Basic Sciences, AU/UGA Medical Partnership, The University of Georgia, Athens, GA, USA

    Jaroslava Halper

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Velchev, J.D., Van Laer, L., Luyckx, I., Dietz, H., Loeys, B. (2021). Loeys-Dietz Syndrome. In: Halper, J. (eds) Progress in Heritable Soft Connective Tissue Diseases. Advances in Experimental Medicine and Biology, vol 1348. Springer, Cham. https://doi.org/10.1007/978-3-030-80614-9_11

Download citation

Publish with us

Policies and ethics

Search

Navigation