eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Marfan Syndrome: Treatment & Medication

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
Contributor Information and Disclosures

Updated: Mar 2, 2010

Treatment

Medical Care

  • General measures for all adults with Marfan syndrome27
    • Moderate restriction of physical activity
    • Endocarditis prophylaxis
    • Echocardiography at annual intervals
    • Beta-blocking treatment
  • Key issues in cardiovascular management10
    • Beta-blocker therapy should be considered at any age if the aorta is dilated, but prophylactic treatment may be more effective in those with an aortic diameter of less than 4 cm. 
    • Risk factors for aortic dissection include aortic diameter greater than 5 cm, aortic dilatation extending beyond the sinus of Valsalva, rapid rate of dilatation (45% per year, or 1.5 mm per y in adults), and family history of aortic dissection. 
    • At least annual evaluation should be offered and should include clinical history, examination, and echocardiography.
    • In children, serial echocardiography at 6-month to 12-month intervals is recommended, and the frequency depends on the aortic diameter (in relation to body surface area) and the rate of increase. 
    • Prophylactic aortic root surgery should be considered when the aortic diameter at the sinus of Valsalva is more than 5 cm.
  • Counseling for pregnancy27
    • Fifty percent risk for transmitting a pathogenic mutation to offspring
    • High-risk pregnancy with aortic root diameter of more than 40 mm or previous cardiovascular surgery or severe heart disease 
    • Prepartum aortic root replacement with diameters of more than 40 mm
    • Serial echocardiography until 3 months postpartum
  • Beta-blockers
    • Beta-adrenergic receptor antagonists have gained acceptance as potential agents for delaying aortic expansion and for delaying the progression to rupture or dissection.
    • The rate of surgical interventions has substantially declined during the past decade of beta-blockade use.
    • Beta-blocker therapy retards aortic growth in children and adolescents with Marfan syndrome.
    • A recent study concluded that data are not sufficient to recommend or discourage the use of beta-blockers in children with congestive heart failure.28
    • Calcium antagonist therapy also retards aortic growth, but a recommended dose has not been established.
    • The optimal age to begin beta-blockade therapy has not been determined. Some investigators begin therapy during infancy, but others wait until the aortic diameter exceeds the 95th percentile or a rapid rate of dilation is observed.
    • In asymptomatic patients, the elastic properties of the aortic root appear to have a heterogeneous response after long-term treatment with atenolol.
    • The stiffness index and distensibility are most likely to be useful when the baseline end-diastolic aortic root diameter is more than 40 mm.
    • More experience is needed to determine the optimal dose of beta-blockers to minimize growth of the aortic root.
  • ACE inhibitors29,30
    • ACE inhibitors reduce central arterial pressure and conduit arterial stiffness and may be useful in Marfan syndrome. This approach received support by a short-term, nonrandomized study comparing enalapril with beta blockade in which stiffness and rate of dilatation improved with the ACE inhibitors.31
    • Another study of patients with Marfan syndrome maintained on beta blockade examined the impact of adding an ACE inhibitor, perindopril, compared with placebo. Over a 24-week period, those receiving the ACE inhibitor had a reduction in aortic stiffness and less absolute change in aortic root dimensions.32
  • Matrix metalloproteinases (MMPs)32,30
    • Syndromes that resemble Marfan syndrome, especially in the potential for aneurysm and dissection, were found to be due to mutations in genes encoding TGF β receptors.18
    • The potential importance of MMPs was stimulated by studies of non-Marfan syndrome abdominal aortic aneurysm in humans and thoracic aortic aneurysm in mice engineered to have Marfan syndrome, in both of which levels of MMP-2 and MMP-9 were raised.33
    • Doxycycline administration to a mouse model of Marfan syndrome suppressed MMPs and improved aortic wall architecture and stiffness compared with atenolol.34
  • Other therapy
    • Anticoagulant medications such as warfarin are needed after artificial heart-valve placement.
    • Intravenous antibiotic therapy is required during cardiac and noncardiac procedures to prevent bacterial endocarditis.
    • Progesterone and estrogen therapy have been used to induce puberty and reduce the patient's ultimate height if hormonal treatment is begun before puberty, but no conclusive data are yet available to show whether this therapy reduces scoliosis.
    • Conservative treatment of protrusio acetabuli mostly involves physiotherapy by forcible stretching (stress fractures of the femoral neck due to stretching are documented),35 weight extension on an abduction frame, local heating, and re-education concerning daily activities.7
    • Myopia is treatable with refraction.
    • Patients with flat feet may wear shoes with adequate arch support, although custom orthotics may be required. Guidelines for the diagnosis and treatment of pediatric flatfoot have been established.36
    • Psychological counseling is helpful for families coping with feelings of denial, anger, blame, depression, or guilt.
  • Future therapeutic strategy
    • The discovery that TGFβ antagonism can rescue aortic aneurysm in C1039G/+ mice prompted the idea to test the efficacy of losartan, a widely used angiotensin II type I receptor (AT1) antagonist, because of its antihypertensive properties and ability to counteract TGFβ in animal models of chronic renal disease and cardiomyopathy.
    • Thus, TGFβ antagonism is a general strategy against aneurysm progression in patients with Marfan syndrome and other disorders of the TGFβ-signaling network.
  • Genetic counseling
    • Affected individuals can transmit the condition to 50% of their offspring.
    • The recurrence risk is 50% if one parent is affected. The recurrence risk is small if neither parent is affected.
    • During counseling, the variability of the disease should be emphasized because an affected child may be more or less affected than the parent.

Surgical Care

  • Indications for prophylactic surgery of the aortic root in adults (at least one criterion)27
    • Aortic root diameter of more than 55 mm (50 mm according to some authors) and aortic root diameter of more than 50 mm (45–50 mm according to some authors) in patients with high risk for aortic complications
      • Family history for aortic dissection
      • Growth of the aortic root of more than 10 mm/y
      • Dilatation of the aortic sinus involving the ascending aorta
      • More than mild aortic regurgitation
      • Severe mitral regurgitation
      • Before major noncardiovascular surgery
      • Women planning pregnancy
    • Aortic ratio of more than 1.5
    • Ratio of the diameters of the aortic root and the descending aorta of more than 2
  • Indications for prophylactic surgery of the aortic root in children27
    • If possible, surgery should be delayed until adolescence
    • Aortic root diameters with similar thresholds as in adults
    • Aortic root diameters outside the upper confidence interval deviate upward from the perused centile on follow-up echocardiograms
  • Cardiovascular surgery
    • Cardiovascular surgery can substantially prolong survival. Prophylactic and emergency cardiovascular surgery is needed for treatment of aortic and mitral regurgitation, aortic aneurysm, and aortic dissection. Emergency surgical replacement of the aortic root is indicated for survivors of acute proximal aortic dissection.
    • The ascending aorta is usually replaced when the aorta exceeds 55-60 mm in diameter. Composite valve-graft replacement is performed, in which the dilated aortic segment is replaced by a prosthetic valve sewn into a tube graft with reimplantation of the coronary ostia (modified Bentall procedure). Composite valve-graft replacement of the aortic root has low rates of morbidity and mortality, produces excellent long-term results, and is currently the treatment of choice for proximal dissection or clinically significant annuloaortic ectasia in patients with Marfan syndrome.
    • An aortic valve–sparing procedure is evolving for patients with an aortic aneurysm and favorable characteristics of the aortic valve and annulus. The advantages of this procedure include the avoidance of anticoagulation and a lowered risk of thromboembolism and endocarditis. The aortic valve–sparing procedure is still controversial because of concerns that it poses a risk of progressive valvular degeneration and annular dilation. Additional long-term data are required before routine use of this procedure can be recommended
  • Scoliosis surgery
    • Severe scoliosis requires surgery. Bracing has a limited role in treating the most severe form of infantile scoliosis.
    • Surgery should not be performed on a child younger than 4 years because many patients with large curves before this age spontaneously die of cardiac complications. Results of spinal fusion are better in children older than 5 years.
    • Indications for surgery in adults include pain, neurologic signs, and thoracic curves greater than 45°, which can cause restrictive lung disease
  • Protrusio acetabuli surgery: This is directed at arresting progression, relieving pain, and restoring the function of the hip through hip replacement with bone grafting of the medial acetabular cavity in older patients and closure of the tri-iradiate cartilage in a child or adolescent.7
  • Pectus repair
    • The shape of the front of the thorax becomes stable and established by mid adolescence. Therefore, repair of pectus excavatum to improve respiratory mechanics should be delayed until then to lessen the risk of recurrence.
    • Pectus carinatum repair is mainly performed for cosmetic reasons
  • Pneumothorax therapy
    • A chest tube is an appropriate initial therapy.
    • After one recurrence, a more aggressive approach involving bleb resection and pleurodesis is recommended.
  • Ocular therapy
    • Lasers can be used to restore a detached retina.
    • The risk of retinal detachment related to lens extraction is increased. The lens is removed only in the following few instances:
      • Dislocation of a lens in the anterior chamber, especially when it touches the corneal endothelium
      • Significant lens opacity
      • Evidence of lens-induced uveitis and glaucoma
      • Inadequate visual acuity that is not correctable by refraction and iris manipulation
      • Imminent complete luxation of the lens

Consultations

  • Clinical geneticist
  • Cardiologist
  • Ophthalmologist
  • Cardiovascular surgeon
  • Orthopedic surgeon
  • Orthodontics surgeon
  • Psychologist

Diet

  • No special diet is needed.

Activity

  • In general, patients can remain fully active unless their symptoms limit them. Patients should be discouraged from participating in demanding sports because several highly trained athletes with unrecognized Marfan syndrome have suddenly died from ruptured aortic aneurysms.
  • Competitive and contact sports are potentially dangerous because of underlying aortic weakness and dilatation, valvular insufficiency, ocular abnormalities, and skeletal problems. Patients should avoid blows to the head (eg, in boxing, high diving) and to protect themselves against blows to the globe (racquet sports) with cushioned spectacles.
  • To protect against pneumothorax, patients should avoid the rapid decompression associated with quick ascents in elevators, scuba diving, and flying in unpressurized aircraft.
  • Patients should avoid activities involving isometric work such as weightlifting, climbing steep inclines, participating in gymnastics, and performing pull-ups. These exercises cause excessive elevations of systolic blood pressure and may lead to sudden death.
  • Nonstrenuous activities and sports (eg, golf, walking, fishing) are recommended. Appropriate exercise is physically and emotionally beneficial.

Medication

Beta-blocker and calcium-antagonist therapy retard the aortic growth rate in children and adolescents with Marfan syndrome. Atenolol, a beta-blocker that is longer acting and more cardioselective than others, has largely replaced propranolol as the beta-blocker of choice. Experience with calcium antagonists is limited.

Beta-adrenergic blocking agents

These drugs are used to delay aortic expansion and its subsequent progression to dissection or rupture. They inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation.


Atenolol (Tenormin)

Selective beta1-adrenergic antagonist.

Adult

25-100 mg/d PO

Pediatric

1-2 mg/kg/d PO qd or divided bid

May potentiate other antihypertensive agents; coadministration with aluminum salts, barbiturates, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease effects; haloperidol, hydralazine, loop diuretics, and MAOIs may increase toxicity

Documented hypersensitivity, sinus bradycardia, second- or third-degree heart block (without a pacemaker), cardiogenic shock, overt cardiac failure, anuria

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May be used with caution in bronchospastic disease; may aggravate peripheral arterial circulatory disorders; use in second trimester may cause fetus to be small for gestational age; patient should take at same time each day and consult physician if concurrently using other adrenergic agonists; gradually taper over 1-2 wk when discontinuing


Propranolol hydrochloride (Inderal)

Nonselective beta-adrenergic antagonist. Has membrane-stabilizing activity and decreases automaticity of contractions.

Adult

120-240 mg/d PO divided q6-8h

Pediatric

1-2 mg/kg/d PO divided q6-12h

Catecholamine-blocking action of drugs (eg, reserpine) may excessively reduce resting sympathetic nervous activity, which may result in hypotension, marked bradycardia, vertigo, syncopal attacks, or orthostatic hypotension; concomitant use with calcium channel blockers may depress myocardial contractility or AV conduction and cause other serious reactions; hypotension and cardiac arrest reported with concomitant haloperidol

Documented hypersensitivity, cardiogenic shock, sinus bradycardia greater than first degree, bronchial asthma, congestive heart failure unless failure is secondary to a tachyarrhythmia treatable with propranolol

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Must carefully titrate dose to patient tolerance and effectiveness; patient should take at same time each day and consult physician if concurrently using any other adrenergic agonists; gradually taper over 1-2 wk when discontinuing

Calcium channel blocking agents

These drugs inhibit the transport of calcium ions across cell membranes.


Verapamil hydrochloride (Calan, Isoptin)

Calcium ion influx inhibitor. Prevents aortic growth in Marfan syndrome.

Adult

80-120 mg PO tid

Pediatric

<2 years: Do not administer
>2 years: Not established

May raise blood alcohol concentration and prolong its effect; additive negative effects on heart rate, AV conduction, and cardiac contractility may occur with concomitant beta-blocker therapy; may interact with antihypertensives, antiarrhythmics (disopyramide, flecainide, quinidine), nitrates, cimetidine, lithium, carbamazepine, rifampin, phenobarbital, cyclosporine, theophylline, inhalation anesthetics, and neuromuscular blocking agents; prolongs recovery from vecuronium

Documented hypersensitivity, severe left ventricular dysfunction, hypotension, cardiogenic shock, sick-sinus syndrome or second- or third-degree AV block (except in patients with functioning artificial ventricular pacemaker), atrial flutter or fibrillation, Wolff-Parkinson-White syndrome, Lown-Ganong-Levine syndrome

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Carefully monitor patients with hepatic dysfunction; use cautiously in impaired renal function; prolongs recovery from neuromuscular blocking agent vecuronium; patients should avoid alcohol and reduce caffeine consumption

More on Marfan Syndrome

Overview: Marfan Syndrome
Differential Diagnoses & Workup: Marfan Syndrome
Treatment & Medication: Marfan Syndrome
Follow-up: Marfan Syndrome
Multimedia: Marfan Syndrome
References
[ CLOSE WINDOW ]

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

  12. 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].

  13. 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].

  14. 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].

  15. 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].

  16. 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].

  17. 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].

  18. 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.

  19. 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].

  20. 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].

  21. 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].

  22. 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].

  23. 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].

  24. 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].

  25. 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].

  26. 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].

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

  28. [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].

  29. 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].

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

  31. 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].

  32. 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].

  33. 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].

  34. 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].

  35. 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].

  36. [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].

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

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

  39. 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].

  40. 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].

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

  42. 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].

  43. 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].

  44. 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].

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

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

  47. 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].

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

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

  50. 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].

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

  52. 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].

  53. 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].

  54. 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].

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

  56. 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].

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

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

  59. 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].

  60. 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.

  61. 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].

  62. 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].

  63. 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.

  64. 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].

  65. 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].

  66. 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].

  67. 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].

  68. 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].

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

  70. 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].

  71. 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].

  72. 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].

  73. 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].

  74. 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.

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

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

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

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

  79. 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].

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

  81. 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].

  82. 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].

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

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

  85. 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].

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

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

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

  89. 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].

  90. 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].

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

  92. 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].

  93. 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].

  94. 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].

  95. 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].

  96. 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].

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

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

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

  100. 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].

  101. 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].

  102. 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].

  103. 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.

  104. 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].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Marfan syndrome, Marfan's syndrome, Marfan disease, Marfan's disease, connective tissue disorder, mitral valve prolapse, mitral regurgitation, aortic root dilatation, chronic aortic regurgitation, treatment, symptoms

[ CLOSE WINDOW ]

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 Medical Association, American Society of Human Genetics, and Teratology Society
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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.

CME Editor

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.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.