SpringerLink
Log in

Clinical Aspects of Heritable Connective Tissue Disorders

  • Chapter
  • First Online:
Surgical Management of Aortic Pathology

  • 1708 Accesses

Abstract

Connective tissue surrounds, supports, and connects a multitude of tissues and organs. It is composed of a cellular component (mostly fibroblasts) and extracellular matrix, with the latter consisting of fibers (collagen, elastic fibrils, etc.) and amorphous glycoproteins. Rare genetic defects in key connective tissue components lead to a heterogeneous group of diseases with multisystem involvement, called heritable connective tissue disorders.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
EUR 29.95
Price includes VAT (Germany)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
EUR 181.89
Price includes VAT (Germany)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
EUR 235.39
Price includes VAT (Germany)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. McKusick V. The cardiovascular aspects of Marfan’s syndrome: a heritable disorder of connective tissue. Circulation. 1955;11:321–42.

    Article  CAS  PubMed  Google Scholar 

  2. Aburawi EH, O’Sullivan J. Relation of aortic root dilatation and age in Marfan’s syndrome. Eur Heart J. 2007;28:376–9.

    Article  PubMed  Google Scholar 

  3. Hwa J, Richards JG, Huang H, McKay D, Pressley L, Hughes CF, et al. The natural history of aortic dilatation in Marfan syndrome. Med J Aust. 1993;158:558–62.

    CAS  PubMed  Google Scholar 

  4. Mimoun L, Detaint D, Hamroun D, Arnoult F, Delorme G, Gautier M, et al. Dissection in Marfan syndrome: the importance of the descending aorta. Eur Heart J. 2011;32:443–9.

    Article  PubMed  Google Scholar 

  5. den Hartog AW, Franken R, Zwinderman AH, Timmermans J, Scholte AJ, van den Berg MP, et al. The risk for type B aortic dissection in Marfan syndrome. J Am Coll Cardiol. 2015;65:246–54.

    Article  Google Scholar 

  6. Kinori M, Wehrli S, Kassem IS, Azar NF, Maumenee IH, Mets MB. Biometry characteristics in adults and children with Marfan syndrome: from the Marfan eye consortium of Chicago. Am J Ophthalmol. 2017;177:144–9.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Maumenee IH. The eye in the Marfan syndrome. Trans Am Ophthalmol Soc. 1981;79:684–733.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Chandra A, Ekwalla V, Child A, Charteris D. Prevalence of ectopia lentis and retinal detachment in Marfan syndrome. Acta Ophthalmol. 2014;92:e82–3.

    Article  PubMed  Google Scholar 

  9. Konradsen TR, Zetterstrom C. A descriptive study of ocular characteristics in Marfan syndrome. Acta Ophthalmol. 2013;91:751–5.

    Article  PubMed  Google Scholar 

  10. Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY, Corson GM, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991;352:337–9.

    Article  CAS  PubMed  Google Scholar 

  11. Verstraeten A, Alaerts M, Van Laer L, Loeys B. Marfan syndrome and related disorders: 25 years of gene discovery. Hum Mutat. 2016;37:524–31.

    Article  CAS  PubMed  Google Scholar 

  12. Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010;47:476–85.

    Article  CAS  PubMed  Google Scholar 

  13. Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005;37:275–81.

    Article  CAS  PubMed  Google Scholar 

  14. Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med. 2006;355:788–98.

    Article  CAS  PubMed  Google Scholar 

  15. Maccarrick G, Black JH 3rd, Bowdin S, El-Hamamsy I, Frischmeyer-Guerrerio PA, Guerrerio AL, et al. Loeys-Dietz syndrome: a primer for diagnosis and management. Genet Med. 2014;16:576–87.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Micha D, Guo DC, Hilhorst-Hofstee Y, van Kooten F, Atmaja D, Overwater E, et al. SMAD2 mutations are associated with arterial aneurysms and dissections. Hum Mutat. 2015;36:1145–9.

    Article  CAS  PubMed  Google Scholar 

  17. van de Laar IM, Oldenburg RA, Pals G, Roos-Hesselink JW, de Graaf BM, Verhagen JM, et al. Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis. Nat Genet. 2011;43:121–6.

    Article  PubMed  Google Scholar 

  18. Lindsay ME, Schepers D, Bolar NA, Doyle JJ, Gallo E, Fert-Bober J, et al. Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. Nat Genet. 2012;44:922–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bertoli-Avella AM, Gillis E, Morisaki H, Verhagen JM, de Graaf BM, van de Beek G, et al. Mutations in a TGF-beta ligand, TGFB3, cause syndromic aortic aneurysms and dissections. J Am Coll Cardiol. 2015;65:1324–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Loeys BL, Dietz HC. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, LJH B, et al., editors. Loeys-Dietz syndrome. Seattle, WA: GeneReviews(R); 2008.

    Google Scholar 

  21. Wenstrup RJ, Meyer RA, Lyle JS, Hoechstetter L, Rose PS, Levy HP, et al. Prevalence of aortic root dilation in the Ehlers-Danlos syndrome. Genet Med. 2002;4:112–7.

    Article  PubMed  Google Scholar 

  22. Beighton P, de Paepe A, Danks D, Finidori G, Gedde-Dahl T, Goodman R, et al. International nosology of heritable disorders of connective tissue, berlin, 1986. Am J Med Genet. 1988;29:581–94.

    Article  CAS  PubMed  Google Scholar 

  23. Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet. 1998;77:31–7.

    Article  CAS  PubMed  Google Scholar 

  24. Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175:8–26.

    Article  PubMed  Google Scholar 

  25. Superti-Furga A, Gugler E, Gitzelmann R, Steinmann B. Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen. J Biol Chem. 1988;263:6226–32.

    CAS  PubMed  Google Scholar 

  26. Pepin MG, Schwarze U, Rice KM, Liu M, Leistritz D, Byers PH. Survival is affected by mutation type and molecular mechanism in vascular Ehlers-Danlos syndrome (EDS type IV). Genet Med. 2014;16:881–8.

    Article  CAS  PubMed  Google Scholar 

  27. Malfait F, Symoens S, De Backer J, Hermanns-Le T, Sakalihasan N, Lapiere CM, et al. 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. 2007;28:387–95.

    Article  CAS  PubMed  Google Scholar 

  28. Schwarze U, Hata R, McKusick VA, Shinkai H, Hoyme HE, Pyeritz RE, et al. 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. 2004;74:917–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Rohrbach M, Vandersteen A, Yis U, Serdaroglu G, Ataman E, Chopra M, et al. Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation. Orphanet J Rare Dis. 2011;6:46.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ha VT, Marshall MK, Elsas LJ, Pinnell SR, Yeowell HN. A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote for mutations in the lysyl hydroxylase gene. J Clin Invest. 1994;93:1716–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Coucke PJ, Willaert A, Wessels MW, Callewaert B, Zoppi N, De Backer J, et al. Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet. 2006;38:452–7.

    Article  CAS  PubMed  Google Scholar 

  32. Willaert A, Khatri S, Callewaert BL, Coucke PJ, Crosby SD, Lee JG, et al. GLUT10 is required for the development of the cardiovascular system and the notochord and connects mitochondrial function to TGFbeta signaling. Hum Mol Genet. 2012;21:1248–59.

    Article  CAS  PubMed  Google Scholar 

  33. Zoppi N, Chiarelli N, Cinquina V, Ritelli M, Colombi M. GLUT10 deficiency leads to oxidative stress and non-canonical alphavbeta3 integrin-mediated TGFbeta signalling associated with extracellular matrix disarray in arterial tortuosity syndrome skin fibroblasts. Hum Mol Genet. 2015;24:6769–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Szabo Z, Crepeau MW, Mitchell AL, Stephan MJ, Puntel RA, Yin Loke K, et al. Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene. J Med Genet. 2006;43:255–8.

    Article  CAS  PubMed  Google Scholar 

  35. Guemann AS, Andrieux J, Petit F, Halimi E, Bouquillon S, Manouvrier-Hanu S, et al. ELN gene triplication responsible for familial supravalvular aortic aneurysm. Cardiol Young. 2015;25:712–7.

    Article  PubMed  Google Scholar 

  36. Zhang MC, He L, Giro M, Yong SL, Tiller GE, Davidson JM. Cutis laxa arising from frameshift mutations in exon 30 of the elastin gene (ELN). J Biol Chem. 1999;274:981–6.

    Article  CAS  PubMed  Google Scholar 

  37. Hucthagowder V, Sausgruber N, Kim KH, Angle B, Marmorstein LY, Urban Z. Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome. Am J Hum Genet. 2006;78:1075–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Hebson C, Coleman K, Clabby M, Sallee D, Shankar S, Loeys B, et al. Severe aortopathy due to fibulin-4 deficiency: molecular insights, surgical strategy, and a review of the literature. Eur J Pediatr. 2014;173:671–5.

    PubMed  Google Scholar 

  39. Gupta PA, Putnam EA, Carmical SG, Kaitila I, Steinmann B, Child A, et al. Ten novel FBN2 mutations in congenital contractural arachnodactyly: delineation of the molecular pathogenesis and clinical phenotype. Hum Mutat. 2002;19:39–48.

    Article  CAS  PubMed  Google Scholar 

  40. Meester JA, Vandeweyer G, Pintelon I, Lammens M, Van Hoorick L, De Belder S, et al. Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections. Genet Med. 2017;19:386–95.

    Article  CAS  PubMed  Google Scholar 

  41. Moutton S, Fergelot P, Naudion S, Cordier MP, Sole G, Guerineau E, et al. Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum. J Hum Genet. 2016;61:693–9.

    Article  CAS  PubMed  Google Scholar 

  42. Sheen VL, Jansen A, Chen MH, Parrini E, Morgan T, Ravenscroft R, et al. Filamin A mutations cause periventricular heterotopia with Ehlers-Danlos syndrome. Neurology. 2005;64:254–62.

    Article  CAS  PubMed  Google Scholar 

  43. Kyndt F, Gueffet JP, Probst V, Jaafar P, Legendre A, Le Bouffant F, et al. Mutations in the gene encoding filamin A as a cause for familial cardiac valvular dystrophy. Circulation. 2007;115:40–9.

    Article  CAS  PubMed  Google Scholar 

  44. Doyle AJ, Doyle JJ, Bessling SL, Maragh S, Lindsay ME, Schepers D, et al. Mutations in the TGF-beta repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm. Nat Genet. 2012;44:1249–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Carmignac V, Thevenon J, Ades L, Callewaert B, Julia S, Thauvin-Robinet C, et al. In-frame mutations in exon 1 of SKI cause dominant Shprintzen-Goldberg syndrome. Am J Hum Genet. 2012;91:950–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Aline Verstraeten & Bart Loeys

Authors
  1. Aline Verstraeten
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bart Loeys
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aline Verstraeten .

Editor information

Editors and Affiliations

  1. Fmr Royal Brompton Hospital, London, UK

    Olaf H. Stanger

  2. Royal Brompton Hospital, London, UK

    John R. Pepper

  3. Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA

    Lars G. Svensson

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer-Verlag GmbH Austria, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Verstraeten, A., Loeys, B. (2019). Clinical Aspects of Heritable Connective Tissue Disorders. In: Stanger, O., Pepper, J., Svensson, L. (eds) Surgical Management of Aortic Pathology. Springer, Vienna. https://doi.org/10.1007/978-3-7091-4874-7_34

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-4874-7_34

  • Published:

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-4872-3

  • Online ISBN: 978-3-7091-4874-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation