Genetics of Marfan Syndrome Workup

  • Author: Harold Chen, MD, MS, FAAP, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Aug 11, 2011
 

Laboratory Studies

Because no common mutations have been identified, genetic testing includes screening the entire FBN1 gene. DNA testing cannot exclude a diagnosis of Marfan syndrome.

  • Molecular studies of the fibrillin gene should be performed in patients in whom Marfan syndrome is suspected.
  • By 1998, 137 FBN1 mutations had been characterized in patients with Marfan syndrome. Mutations are distributed throughout the FBN1 gene.
  • Most mutations are missense mutations, small in-frame deletions, or insertions that alter a single peptide of about 3000 amino acids.
  • All mutations described to this point are predicted to produce a mutant fibrillin-1 protein.
  • Mutation analysis can identify the exact mutation in the fibrillin gene, and linkage analysis can be used to track an abnormal fibrillin gene within a family.
  • Sequencing of the entire gene for the purpose of detecting mutations is tedious and expensive. Mutations detected using sequencing may represent normal variations, resulting in both false-positive and false-negative results.
  • Molecular diagnosis is commercially available by sequencing of entire coding region or select exons, by mutations scanning, by performing targeted mutation analysis, by conducting linkage analysis, and by sequencing RNA.
  • A comprehensive clinical and molecular description of a large series of pediatric cases with a FBN1 mutation.[28] Besides lethal neonatal Marfan syndrome, which represents a genuine entity, most clinical manifestations of Marfan syndrome increase with age, highlighting the limited usefulness of international criteria for diagnosis in early infancy and emphasizing the value of FBN1 mutation screening, which not only confirms the diagnosis but also facilitates determination of prognosis and timely management.
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Imaging Studies

Advances in noninvasive diagnostic imaging modalities have had a profound influence on case management. These studies provide accurate detection and quantification of the severity of cardiovascular disease, aiding in the appropriate timing of surgical intervention.

  • Radiography
    • Chest radiography should be focused on apical blebs. Chest radiographs may also be of value in detecting a thoracic aortic dissection by demonstrating enlargement of the aortic and cardiac silhouette.
    • Pelvic radiography is required only if a positive finding of protrusio acetabula is needed for the diagnosis.
  • Echocardiography
    • Cross-sectional echocardiography is a common tool in the diagnosis and management of aortic root dilatation. The upper limit of the normal aortic root size is 1.9 cm/m2 of body surface area and is independent of the patient's sex.
    • Standard echocardiography is valuable in assessing mitral valve prolapse, left ventricular size and function, left atrial size, and function of the tricuspid valve.
    • Transesophageal echocardiography depicts the distal ascending and descending aorta. It also improves assessment of the prosthetic valves.
    • Doppler echocardiography is useful in detecting and grading the severity of aortic and mitral regurgitation.
  • CT and MRI
    • MRI is the best choice for assessing chronic dissection of any region of the aorta. It should be performed in any patient at any age who has an aortic root dimension of more than 150% of the mean for their body surface area or a ratio of actual to predicted aortic root dimension of more than 1.5.
    • CT or MRI of the lumbosacral spine may be needed to detect dural ectasia. The following MRI and CT criteria for dural ectasia in adults have been proposed:
      • Presence of dural ectasia requires one major criterion or both minor criteria
      • Major criterion - Sagittal width of the dural sac at S1 or below that is greater than the sagittal width of the dural sac above L4
      • Minor criteria - Nerve root sleeve at L5 of more than 6.5 mm in diameter or scalloping at S1 of more than 3.5 mm
  • Aortography
    • Many still consider this procedure the criterion standard for diagnosing acute aortic dissection.
    • However, the sensitivity is not 100%, and aortography has associated risks.
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Other Tests

An ambulatory electrocardiogram should be obtained in patients with symptomatic palpitations, syncope, or near syncope or a baseline ECG that shows major rhythm or conduction disturbance.

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Procedures

Measure blood pressure.

Upon slit-lamp examination, the patient's pupils should be dilated and checked for lens dislocation and any sign of retinal tears.

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Histologic Findings

Immunohistologic evaluation of the skin for abnormal fibrillin has been reported but is not widely available in the United States. This is partly due to the high incidence of false-positive results in patients with other connective-tissue disorders who have symptoms and signs of Marfan syndrome.

Electron microscopy of fibrillin from cultured fibroblasts has shown a substantial increase in fraying of microfibrils in patients with Marfan syndrome. In neonatal Marfan syndrome, electron microscopy of fibrillin strands reveals only beads that are not strung together in the usual necklacelike pattern, resulting in poor elastic tissue strength.

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Contributor Information and Disclosures
Author

Harold Chen, MD, MS, FAAP, FACMG  Professor, Departments of Pediatrics, Obstetrics and Gynecology, and Pathology, Director of Genetic Laboratory Services, Louisiana State University Medical Center

Harold Chen, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, American Medical Association, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

James Bowman, MD  Senior Scholar of Maclean Center for Clinical Medical Ethics, Professor Emeritus, Department of Pathology, University of Chicago

James Bowman, MD is a member of the following medical societies: Alpha Omega Alpha, American Society for Clinical Pathology, American Society of Human Genetics, Central Society for Clinical Research, and College of American Pathologists

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Leonard G Feld, MD, PhD, MMM, FAAP  Sara H Bissell and Howard C Bissell Endowed Chair in Pediatrics, Chief Medical Officer, Levine Children's Hospital, Carolinas Medical Center

Leonard G Feld, MD, PhD, MMM, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Juvenile Diabetes Foundation International

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

  1. Loeys BL, Chen J, Neptune ER, et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. Mar 2005;37(3):275-81. [Medline].

  2. Lee B, Godfrey M, Vitale E, et al. Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 1991;352:337-339.

  3. Pyeritz RE. The Marfan syndrome. Annu Rev Med. 2000;51:481-510. [Medline].

  4. Rose PS, Levy HP, Ahn NU, et al. A comparison of the Berlin and Ghent nosologies and the influence of dural ectasia in the diagnosis of Marfan syndrome. Genet Med. Oct 2000;2(5):278-82. [Medline].

  5. Van de Velde S, Fillman R, Yandow S. Protrusio acetabuli in Marfan syndrome. History, diagnosis, and treatment. J Bone Joint Surg Am. Mar 2006;88(3):639-46. [Medline].

  6. Jones KB, Sponseller PD, Erkula G, et al. Symposium on the musculoskeletal aspects of Marfan syndrome: meeting report and state of the science. J Orthop Res. Mar 2007;25(3):413-22. [Medline].

  7. Avivi E, Arzi H, Paz L, Caspi I, Chechik A. Skeletal manifestations of Marfan syndrome. Isr Med Assoc J. Mar 2008;10(3):186-8. [Medline]. [Full Text].

  8. Altman A, Uliel L, Caspi L. Dural ectasia as presenting symptom of Marfan syndrome. Isr Med Assoc J. Mar 2008;10(3):194-5. [Medline]. [Full Text].

  9. Lacassie HJ, Millar S, Leithe LG, et al. Dural ectasia: a likely cause of inadequate spinal anaesthesia in two parturients with Marfan's syndrome. Br J Anaesth. Apr 2005;94(4):500-4. [Medline].

  10. Dean JC. Marfan syndrome: clinical diagnosis and management. Eur J Hum Genet. May 9 2007;[Medline].

  11. Loeys BL, Dietz HC, Braverman AC, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. Jul 2010;47(7):476-85. [Medline].

  12. Faivre L, Collod-Beroud G, Ades L, et al. The new Ghent criteria for Marfan syndrome: what do they change?. Clin Genet. May 12 2011;[Medline].

  13. Frydman M. The Marfan syndrome. Isr Med Assoc J. Mar 2008;10(3):175-8. [Medline]. [Full Text].

  14. Tiecke F, Katzke S, Booms P, et al. Classic, atypically severe andneonatal Marfan syndrome: twelve mutations and genotype-phenotypecorrelations in FBN1 exons 24-40. Eur J Hum Genet. 2001;9:13-21. [Medline]. [Full Text].

  15. de Vries BB, Pals G, Odink R, Hamel BC. Homozygosity for a FBN1 missense mutation: clinical and molecular evidence for recessive Marfan syndrome. Eur J Hum Genet. Sep 2007;15(9):930-5. [Medline].

  16. Callewaert B, Malfait F, Loeys B, De Paepe A. Ehlers-Danlos syndromes and Marfan syndrome. Best Pract Res Clin Rheumatol. Mar 2008;22(1):165-89. [Medline].

  17. Gupta PA, Wallis DD, Chin TO, et al. FBN2 mutation associated with manifestations of Marfan syndrome and congenital contractural arachnodactyly. J Med Genet. May 2004;41(5):e56. [Medline].

  18. Putnam EA, Zhang H, Ramirez F, Milewicz DM. Fibrillin-2 (FBN2) mutations result in the Marfan-like disorder, congenital contractural arachnodactyly. Nat Genet. Dec 1995;11(4):456-8. [Medline].

  19. Lieberman ER, Gomperts ED, Shaw KN, Landing BH, Donnell GN. Homocystinuria: clinical and pathologic review, with emphasis on thrombotic features, including pulmonary artery thrombosis. Perspect Pediatr Pathol. 1993;17:125-47. [Medline].

  20. Loeys BL, Schwarze U, Holm T, et al. Aneurysm syndromes caused by mutations in the TGF-betareceptor. New Engl J Med. 2006;355:788-798.

  21. Glesby MJ, Pyeritz RE. Association of mitral valve prolapse and systemic abnormalities of connective tissue. A phenotypic continuum. JAMA. Jul 28 1989;262(4):523-8. [Medline].

  22. Montgomery RA, Geraghty MT, Bull E, Gelb BD, Johnson M, McIntosh I, et al. Multiple molecular mechanisms underlying subdiagnostic variants of Marfan syndrome. Am J Hum Genet. Dec 1998;63(6):1703-11. [Medline].

  23. Sood S, Eldadah ZA, Krause WL, McIntosh I, Dietz HC. Mutation in fibrillin-1 and the Marfanoid-craniosynostosis (Shprintzen-Goldberg) syndrome. Nat Genet. Feb 1996;12(2):209-11. [Medline].

  24. Raymond FL, Tarpey PS, Edkins S, et al. Mutations in ZDHHC9, which encodes a palmitoyltransferase of NRAS and HRAS, cause X-linked mental retardation associated with a Marfanoid habitus. Am J Hum Genet. May 2007;80(5):982-7. [Medline].

  25. Schwartz CE, Tarpey PS, Lubs HA, et al. The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene. J Med Genet. Jul 2007;44(7):472-7. [Medline].

  26. Faivre L, Gorlin RJ, Wirtz MK, et al. In frame fibrillin-1 gene deletion in autosomal dominant Weill-Marchesani syndrome. J Med Genet. Jan 2003;40(1):34-6. [Medline].

  27. Dagoneau N, Benoist-Lasselin C, Huber C, et al. ADAMTS10 mutations in autosomal recessive Weill-Marchesani syndrome. Am J Hum Genet. Nov 2004;75(5):801-6. [Medline].

  28. Faivre L, Masurel-Paulet A, Collod-Béroud G, Callewaert BL, Child AH, Stheneur C, et al. Clinical and molecular study of 320 children with Marfan syndrome and related type I fibrillinopathies in a series of 1009 probands with pathogenic FBN1 mutations. Pediatrics. Jan 2009;123(1):391-8. [Medline].

  29. von Kodolitsch Y, Robinson PN. Marfan syndrome: an update of genetics, medical and surgical management. Heart. Jun 2007;93(6):755-60. [Medline].

  30. [Best Evidence] Frobel AK, Hulpke-Wette M, Schmidt KG, Laer S. Beta-blockers for congestive heart failure in children. Cochrane Database Syst Rev. Jan 21 2009;CD007037. [Medline].

  31. Williams A, Davies S, Stuart AG, Wilson DG, Fraser AG. Medical treatment of Marfan syndrome: a time for change. Heart. Apr 2008;94(4):414-21. [Medline].

  32. Pyeritz RE. Marfan syndrome: 30 years of research equals 30 years of additional life expectancy. Heart. Mar 2009;95(3):173-5. [Medline].

  33. Yetman AT, Bornemeier RA, McCrindle BW. Usefulness of enalapril versus propranolol or atenolol for prevention of aortic dilation in patients with the Marfan syndrome. Am J Cardiol. May 1 2005;95(9):1125-7. [Medline].

  34. Ahimastos AA, Aggarwal A, D'Orsa KM, et al. Effect of perindopril on large artery stiffness and aortic root diameter in patients with Marfan syndrome: a randomized controlled trial. JAMA. Oct 3 2007;298(13):1539-47. [Medline].

  35. Chung AW, Yang HH, Radomski MW, van Breemen C. Long-term doxycycline is more effective than atenolol to prevent thoracic aortic aneurysm in marfan syndrome through the inhibition of matrix metalloproteinase-2 and -9. Circ Res. Apr 25 2008;102(8):e73-85. [Medline].

  36. Chung AW, Au Yeung K, Sandor GG, Judge DP, Dietz HC, van Breemen C. Loss of elastic fiber integrity and reduction of vascular smooth muscle contraction resulting from the upregulated activities of matrix metalloproteinase-2 and -9 in the thoracic aortic aneurysm in Marfan syndrome. Circ Res. Aug 31 2007;101(5):512-22. [Medline].

  37. Kharrazi FD, Rodgers WB, Coran DL, Kasser JR, Hall JE. Protrusio acetabuli and bilateral basicervical femoral neck fractures in a patient with Marfan syndrome. Am J Orthop. Oct 1997;26(10):689-91. [Medline].

  38. [Guideline] Harris EJ, Vanore JV, Thomas JL, et al. Diagnosis and treatment of pediatric flatfoot. J Foot Ankle Surg. Nov-Dec 2004;43(6):341-73. [Medline].

  39. Stout M. The Marfan syndrome: implications for athletes and their echocardiographic assessment. Echocardiography. Oct 2009;26(9):1075-81. [Medline].

  40. Ageno W, Crotti S, Turpie AG. The safety of antithrombotic therapy during pregnancy. Expert Opin Drug Saf. Mar 2004;3(2):113-8. [Medline].

  41. Lev-Ran O, Kramer A, Gurevitch J, Shapira I, Mohr R. Low-molecular-weight heparin for prosthetic heart valves: treatment failure. Ann Thorac Surg. Jan 2000;69(1):264-5; discussion 265-6. [Medline].

  42. Meijboom LJ, Vos FE, Timmermans J, Boers GH, Zwinderman AH, Mulder BJ. Pregnancy and aortic root growth in the Marfan syndrome: a prospective study. Eur Heart J. May 2005;26(9):914-20. [Medline].

  43. Goland S, Elkayam U. Cardiovascular problems in pregnant women with marfan syndrome. Circulation. Feb 3 2009;119(4):619-23. [Medline].

  44. Goland S, Barakat M, Khatri N, Elkayam U. Pregnancy in Marfan syndrome: maternal and fetal risk and recommendations for patient assessment and management. Cardiol Rev. Nov-Dec 2009;17(6):253-62. [Medline].

  45. Ahn NU, Sponseller PD, Ahn UM, et al. Dural ectasia in the Marfan syndrome: MR and CT findings and criteria. Genet Med. May-Jun 2000;2(3):173-9. [Medline].

  46. Ahn NU, Sponseller PD, Ahn UM, et al. Dural ectasia is associated with back pain in Marfan syndrome. Spine. Jun 15 2000;25(12):1562-8. [Medline].

  47. Alpert BS. Tall stature. Pediatr Rev. Sep 1998;19(9):303-5. [Medline].

  48. American Academy of Pediatrics Committee on Genetics. Health supervision for children with Marfan syndrome. Pediatrics. Nov 1996;98(5):978-82. [Medline].

  49. Beighton P, de Paepe A, Danks D, et al. International Nosology of Heritable Disorders of Connective Tissue, Berlin, 1986. Am J Med Genet. Mar 1988;29(3):581-94. [Medline].

  50. Boileau C, Jondeau G, Mizuguchi T, Matsumoto N. Molecular genetics of Marfan syndrome. Curr Opin Cardiol. May 2005;20(3):194-200. [Medline].

  51. Braverman AC. Exercise and the Marfan syndrome. Med Sci Sports Exerc. Oct 1998;30(10 Suppl):S387-95. [Medline].

  52. Brooke BS, Habashi JP, Judge DP, Patel N, Loeys B, Dietz HC 3rd. Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. N Engl J Med. Jun 26 2008;358(26):2787-95. [Medline].

  53. Chen H. Marfan syndrome. In: Atlas of Genetic Diagnosis and Counseling. Totowa, New Jersey: Humana Press; 2006:619-629.

  54. Collod-Beroud G, Beroud C, Ades L, et al. Marfan Database (third edition): new mutations and new routines for the software. Nucleic Acids Res. Jan 1 1998;26(1):229-3. [Medline]. [Full Text].

  55. Coselli JS, LeMaire SA, Buket S. Marfan syndrome: the variability and outcome of operative management. J Vasc Surg. Mar 1995;21(3):432-43. [Medline].

  56. David TE. Current practice in Marfan's aortic root surgery: reconstruction with aortic valve preservation or replacement? What to do with the mitral valve?. J Card Surg. Mar-Apr 1997;12(2 Suppl):147-50. [Medline].

  57. De Paepe A. Dural ectasia and the diagnosis of Marfan's syndrome. Lancet. Sep 11 1999;354(9182):878-9. [Medline].

  58. De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet. Apr 24 1996;62(4):417-26. [Medline].

  59. Demetracopoulos CA, Sponseller PD. Spinal deformities in Marfan syndrome. Orthop Clin North Am. Oct 2007;38(4):563-72, vii. [Medline].

  60. Dietz HC. Marfan syndrome. GeneReviews [GeneTests Web site]. Available at: www.genetests.com. 2003;[Full Text].

  61. Dietz HC, Pyeritz RE. Mutations in the human gene for fibrillin-1 (FBN1) in the Marfan syndrome and related disorders. Hum Mol Genet. 1995;4 Spec No:1799-809. [Medline].

  62. Dietz HC, Pyeritz RE. Marfan syndrome and related disorders. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 2001:5287-311.

  63. Fattori R, Nienaber CA, Descovich B, et al. Importance of dural ectasia in phenotypic assessment of Marfan's syndrome. Lancet. Sep 11 1999;354(9182):910-3. [Medline].

  64. Gelb BD. Marfan's syndrome and related disorders--more tightly connected than we thought. N Engl J Med. Aug 24 2006;355(8):841-4. [Medline].

  65. Godfrey M. The Marfan syndrome. In: Beighton P, ed. McKusick's Heritable Disorders of Connective Tissue. 5th ed. St Louis, MO: Mosby; 1993:51-135.

  66. Ha HI, Seo JB, Lee SH, Kang JW, Goo HW, Lim TH, et al. Imaging of Marfan syndrome: multisystemic manifestations. Radiographics. Jul-Aug 2007;27(4):989-1004. [Medline].

  67. Habashi JP, Judge DP, Holm TM, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. Apr 7 2006;312(5770):117-21. [Medline].

  68. Habermann CR, Weiss F, Schoder V, et al. MR evaluation of dural ectasia in Marfan syndrome: reassessment of the established criteria in children, adolescents, and young adults. Radiology. Feb 2005;234(2):535-41. [Medline].

  69. Hayward C, Porteous ME, Brock DJ. Mutation screening of all 65 exons of the fibrillin-1 gene in 60 patients with Marfan syndrome: report of 12 novel mutations. Hum Mutat. 1997;10(4):280-9. [Medline].

  70. Igondjo-Tchen S, Pages N, Bac P, Godeau G, Durlach J. Marfan syndrome, magnesium status and medical prevention of cardiovascular complications by hemodynamic treatments and antisense gene therapy. Magnes Res. Mar 2003;16(1):59-64. [Medline].

  71. Kousseff BG, Jennings JW, Ranells JD. The revised diagnostic criteria of Marfan syndrome: a clinical analysis [abstract]. Am J Hum Genet. 1999;65:A36.

  72. Lacro RV, Dietz HC, Wruck LM, et al. 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. Oct 2007;154(4):624-31. [Medline].

  73. Ladouceur M, Fermanian C, Lupoglazoff JM, et al. Effect of beta-blockade on ascending aortic dilatation in children with the Marfan syndrome. Am J Cardiol. Feb 1 2007;99(3):406-9. [Medline].

  74. LeMaire SA, Coselli JS. Aortic root surgery in Marfan syndrome: current practice and evolving techniques. J Card Surg. Mar-Apr 1997;12(2 Suppl):137-41. [Medline].

  75. Lipscomb KJ, Smith JC, Clarke B, Donnai P, Harris R. Outcome of pregnancy in women with Marfan's syndrome. Br J Obstet Gynaecol. Feb 1997;104(2):201-6. [Medline].

  76. Marfan AB. Un cas de deformation congenitale des quatre membres plus prononcee aux extremites caracterisee par l'allongement des os avec un certain degre d'amincissement. Bull Mem Soc Med Hop Paris (ser 3). 1896;13:220-6.

  77. Maumenee IH. The eye in the Marfan syndrome. Trans Am Ophthalmol Soc. 1981;79:684-733. [Medline].

  78. Milewicz DM. Molecular genetics of Marfan syndrome and Ehlers-Danlos type IV. Curr Opin Cardiol. May 1998;13(3):198-204. [Medline].

  79. Mizuguchi T, Collod-Beroud G, Akiyama T, et al. Heterozygous TGFBR2 mutations in Marfan syndrome. Nat Genet. Aug 2004;36(8):855-60. [Medline].

  80. National Marfan Foundation. National Marfan Foundation Southern California Chapter: Marfan Syndrome Resource Manual. Available at www.marfan.org. 1999. [Full Text].

  81. Nemet AY, Assia EI, Apple DJ, Barequet IS. Current concepts of ocular manifestations in Marfan syndrome. Surv Ophthalmol. Nov-Dec 2006;51(6):561-75. [Medline].

  82. Nollen GJ, Mulder BJ. What is new in the Marfan syndrome?. Int J Cardiol. Dec 2004;97 Suppl 1:103-8. [Medline].

  83. Pearson GD, Devereux R, Loeys B, et al. Report of the National Heart, Lung, and Blood Institute and National Marfan Foundation Working Group on research in Marfan syndrome and related disorders. Circulation. Aug 12 2008;118(7):785-91. [Medline].

  84. Pereira L, Levran O, Ramirez F, et al. A molecular approach to the stratification of cardiovascular risk in families with Marfan's syndrome. N Engl J Med. Jul 21 1994;331(3):148-53. [Medline].

  85. Pyeritz RE. The Marfan syndrome. In: Heritable Connective Tissue and Its Disorders. New York, NY: Wiley-Liss; 1993:437-68.

  86. Pyeritz RE. The Marfan syndrome in childhood: features, natural history and differential diagnosis. Prog Pediatr Cardiol. 1996;5:151-7.

  87. Pyeritz RE, Fishman EK, Bernhardt BA, Siegelman SS. Dural ectasia is a common feature of the Marfan syndrome. Am J Hum Genet. Nov 1988;43(5):726-32. [Medline].

  88. Pyeritz RE, McKusick VA. The Marfan syndrome: diagnosis and management. N Engl J Med. Apr 5 1979;300(14):772-7. [Medline].

  89. Raanani E, Ghosh P. The multidisciplinary approach to the Marfan patient. Isr Med Assoc J. Mar 2008;10(3):171-4. [Medline]. [Full Text].

  90. Ramirez F, Dietz HC. Marfan syndrome: from molecular pathogenesis to clinical treatment. Curr Opin Genet Dev. Apr 26 2007;[Medline].

  91. Rios AS, Silber EN, Bavishi N, et al. Effect of long-term beta-blockade on aortic root compliance in patients with Marfan syndrome. Am Heart J. Jun 1999;137(6):1057-61. [Medline].

  92. Robinson PN, Arteaga-Solis E, Baldock C, et al. The molecular genetics of Marfan syndrome and related disorders. J Med Genet. Oct 2006;43(10):769-87. [Medline].

  93. Roman MJ, Devereux RB. Diagnostic imaging of the cardiovascular system in the Marfan syndrome. Prog Pediatr Cardiol. 1996;5:175-88.

  94. Rossi-Foulkes R, Roman MJ, Rosen SE, et al. Phenotypic features and impact of beta blocker or calcium antagonist therapy on aortic lumen size in the Marfan syndrome. Am J Cardiol. May 1 1999;83(9):1364-8. [Medline].

  95. Salim MA, Alpert BS, Ward JC, Pyeritz RE. Effect of beta-adrenergic blockade on aortic root rate of dilation in the Marfan syndrome. Am J Cardiol. Sep 15 1994;74(6):629-33. [Medline].

  96. Shores J, Berger KR, Murphy EA, Pyeritz RE. Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan's syndrome. N Engl J Med. May 12 1994;330(19):1335-41. [Medline].

  97. Silverman DI, Burton KJ, Gray J, et al. Life expectancy in the Marfan syndrome. Am J Cardiol. Jan 15 1995;75(2):157-60. [Medline].

  98. Spits C, De Rycke M, Van Ranst N, et al. Preimplantation genetic diagnosis for cancer predisposition syndromes. Prenat Diagn. May 2007;27(5):447-56. [Medline].

  99. Sponseller PD, Sethi N, Cameron DE, Pyeritz RE. Infantile scoliosis in Marfan syndrome. Spine. Mar 1 1997;22(5):509-16. [Medline].

  100. Stern WE. Dural ectasia and the Marfan syndrome. J Neurosurg. Aug 1988;69(2):221-7. [Medline].

  101. Stuart AG, Williams A. Marfan's syndrome and the heart. Arch Dis Child. Apr 2007;92(4):351-6. [Medline].

  102. Summers KM, West JA, Peterson MM, et al. Challenges in the diagnosis of Marfan syndrome. Med J Aust. Jun 19 2006;184(12):627-31. [Medline].

  103. Van Tongerloo A, De Paepe A. Psychosocial adaptation in adolescents and young adults with Marfan syndrome: an exploratory study. J Med Genet. May 1998;35(5):405-9. [Medline].

  104. Villeirs GM, Van Tongerloo AJ, Verstraete KL, Kunnen MF, De Paepe AM. Widening of the spinal canal and dural ectasia in Marfan's syndrome: assessment by CT. Neuroradiology. Nov 1999;41(11):850-4. [Medline].

  105. Wang M, Godfrey M. Prenatal and presymptomatic diagnosis of Marfan syndrome using fluorescence PCR and an automated sequencer. In: Methods in Molecular Biology. Totowa, NJ: Humana Press; 1998:49-54.

  106. Weigang E, Ghanem N, Chang XC, et al. Evaluation of three different measurement methods for dural ectasia in Marfan syndrome. Clin Radiol. Nov 2006;61(11):971-8. [Medline].

 
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Adult with Marfan syndrome. Note tall and thin build, disproportionately long arms and legs, and kyphoscoliosis.
Positive wrist (Walker) sign.
Positive thumb (Steinberg) sign.
Arachnodactyly.
Pectus excavatum of moderate severity.
Hypermobility of finger joints.
Stretch marks (striae atrophicae) in the lower back.
Dural ectasia in the lumbosacral region.
 
 
 
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