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Marfan syndrome

Marfan syndrome has been suggested in at least 2 historical figures, Abraham lincoln & Paganini. Epidemiology: 1) incidence 1 in 10,000 2) autosomal dominant 3) at least 25% of patients do not have affected parent (presumably due to new mutations) Pathology: 1) myxomatous change of the mitral valve is common a) leaflet thickening b) chordal elongation c) spontaneous chordal rupture d) annular enlargement with mitral regurgitation e) increased risk of endocarditis 2) aortic & mitral valvular incompetence 3) aortic dilatation with aortic aneurysm 4) dissecting aortic aneurysm frequently cause of death Genetics: - autosomal dominant - associated with defects in FBN1 Clinical manifestations: 1) musculoskeletal manifestations: a) tall, slender stature b) arm span exceeds height (dolichostenomelia, ratio > 1.05) c) long digits (arachnodactyly) d) thumb sign (distal phalanx protrudes beyond border of clenched fist) e) wrist sign (thumb & 5th digit overlap when around the wrist) f) sternal deformity, pigeon breast or funnel breast (pectus excavatum) g) reduced elbow extension (< 170 degrees) h) kyphoscoliosis, thoracolumbar scoliosis i) erosion of lumbosacral vertebrae due to dural ectasia j) hammer toes k) long, narrow skull l) oral cavity 1] crowded dentition 2] high arched palate 3] mandible malocclusion 2) ocular manifestations: a) lenticular subluxations with diminished vision (ectopia lentis) b) myopia c) cataracts d) blue sclera [5] 3) pulmonary manifestations (10%) a) emphysema b) bullous lung disease c) spontaneous pneumothorax (5%) d) upper lobe fibrosis e) bronchiectasis 4) cardiovascular manifestations a) aortic aneurysm, aortic dissection b) aortic root dilation c) mitral valve prolapse 5) central nervous system manifestations - dural ectasia 6) skin manifestations - hyperextensibility of skin - atrophic scarring over pectoral, deltoid or lumbar regions [5] Laboratory: 1) homocystinuria 2) detection of fibrillin defects in cultured fibroblasts (not yet available) 3) DNA analysis (not yet available) Special laboratory: - echocardiogram a) baseline, at 6 months, then annually if aortic size remains stable; consider more frequent imaging if aortic root diameter >= 4.5 cm [5] b) enlargement of aortic root c) mitral valve abnormalities common - annual ophthalmic examination Radiology: - thoracic CT or MRI - deformities of aorta & pulmonary artery - indicated prior to surgery - lumbosacral CT or MRI - lumbosacral dural ectasia Complications: - aortic root dilation & dissection are the primary cause of death [9] - obstructive sleep apnea occurs with a higher prevalence in Marfan's syndrome - spontaneous pneumothorax Management: 1) no established treatment 2) cardiovascular disorders a) beta-blocker or ACE inhibitor/ARB to prevent or slow aortic root dilation & dissection - atenolol & losartan equally effective [9] b) regular monitoring with echocardiography 1] immediately after diagnosis 2] repeat in 6 months to assess progression 3] then every 2 years c) surgical repair or replacement of aorta when aortic root is > 5.0 cm [5,6] d) surgical repair or replacement of aortic valve &/or mitral valve as indicated e) pregnancy increases risk of aortic dissection [5] - stability of ascending aorta >= 6 months - aortic dilation > 5 mm/year high risk - ascending aorta diameter of <= 4.0 cm considered safe [5] - repair of ascending aortic aneurysm >= 4.0 cm prior to pregnancy [5] - repair of ascending aortic aneurysm prior to pregnancy if - aortic dilation > 5 mm/year [5] - family or personal history of aortic dissection - preconception genetic counseling indicated 3) treatment of scoliosis a) mechanical bracing & physical therapy if > 20 degrees b) surgery if > 50 degrees c) estrogen has been tried in girls with scoliosis 4) eye disorders a) dislocated lenses rarely require surgical removal b) patient should be monitored for retinal detachment 5) endocarditis prophylaxis for mitral valve disorder

General

genetic syndrome (multisystem disorder)

Database Correlations

OMIM correlations MORBIDMAP 134797

References

  1. DeGowin & DeGowin's Diagnostic Examination, 6th edition, RL DeGowin (ed), McGraw Hill, NY 1994, pg 909
  2. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, 2192-93
  3. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 757
  4. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1038, 2115-16
  5. Medical Knowledge Self Assessment Program (MKSAP) 15,16,17,18,19. American College of Physicians, Philadelphia 2009,2012,2015,2018, 2018. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  6. Stout M. The Marfan syndrome: implications for athletes and their echocardiographic assessment. Echocardiography. 2009 Oct;26(9):1075-81. PMID: 19840071
  7. Judge DP, Dietz HC. Marfan's syndrome. Lancet. 2005 Dec 3;366(9501):1965-76. PMID: 16325700
  8. Callewaert B, Malfait F, Loeys B, De Paepe A. Ehlers-Danlos syndromes and Marfan syndrome. Best Pract Res Clin Rheumatol. 2008 Mar;22(1):165-89. PMID: 18328988
  9. Lacro RV et al. Atenolol versus losartan in children and young adults with Marfan's syndrome. N Engl J Med 2014 Nov 18 PMID: 25405392 http://www.nejm.org/doi/full/10.1056/NEJMoa1404731
  10. Dean JC Marfan syndrome: clinical diagnosis and management. Eur J Hum Genet. 2007 Jul;15(7):724-33. Epub 2007 May 9. PMID: 17487218
  11. Jondeau G, Detaint D, Tubach F et al Aortic event rate in the Marfan population: a cohort study. Circulation. 2012 Jan 17;125(2):226-32 PMID: 22133496
  12. National Heart, Lung, and Blood Institute (NHLBI) Marfan Syndrome https://www.nhlbi.nih.gov/health-topics/marfan-syndrome