Marfan syndrome
Jump to navigation
Jump to search
Introduction
Marfan syndrome has been suggested in at least 2 historical figures, Abraham lincoln & Paganini.
Epidemiology
- incidence 1 in 10,000
- autosomal dominant
- at least 25% of patients do not have affected parent (presumably due to new mutations)
Pathology
- myxomatous change of the mitral valve is common
- leaflet thickening
- chordal elongation
- spontaneous chordal rupture
- annular enlargement with mitral regurgitation
- increased risk of endocarditis
- aortic & mitral valvular incompetence
- aortic dilatation with aortic aneurysm
- dissecting aortic aneurysm frequently cause of death
Genetics
- autosomal dominant
- associated with defects in FBN1
Clinical manifestations
- musculoskeletal manifestations:
- tall, slender stature
- arm span exceeds height (dolichostenomelia, ratio > 1.05)
- long digits (arachnodactyly)
- thumb sign (distal phalanx protrudes beyond border of clenched fist)
- wrist sign (thumb & 5th digit overlap when around the wrist)
- sternal deformity, pigeon breast or funnel breast (pectus excavatum)
- reduced elbow extension (< 170 degrees)
- kyphoscoliosis, thoracolumbar scoliosis
- erosion of lumbosacral vertebrae due to dural ectasia
- hammer toes
- long, narrow skull
- oral cavity
- crowded dentition
- high arched palate
- mandible malocclusion
- ocular manifestations:
- lenticular subluxations with diminished vision (ectopia lentis)
- myopia
- cataracts
- blue sclera[5]
- pulmonary manifestations (10%)
- emphysema
- bullous lung disease
- spontaneous pneumothorax (5%)
- upper lobe fibrosis
- bronchiectasis
- cardiovascular manifestations
- central nervous system manifestations - dural ectasia
- skin manifestations
- hyperextensibility of skin
- atrophic scarring over pectoral, deltoid or lumbar regions[5]
Laboratory
- homocystinuria
- detection of fibrillin defects in cultured fibroblasts (not yet available)
- DNA analysis (not yet available)
Diagnostic procedures
- echocardiogram
- baseline, at 6 months, then annually if aortic size remains stable; consider more frequent imaging if aortic root diameter >= 4.5 cm[5]
- enlargement of aortic root
- 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
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
- no established treatment
- cardiovascular disorders
- beta-blocker or ACE inhibitor/ARB to prevent or slow aortic root dilation & dissection
- regular monitoring with echocardiography
- immediately after diagnosis
- repeat in 6 months to assess progression
- then every 2 years
- surgical repair or replacement of aorta when aortic root is > 5.0 cm[5][6]
- surgical repair or replacement of aortic valve &/or mitral valve as indicated
- 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
- stability of ascending aorta >= 6 months
- treatment of scoliosis
- mechanical bracing & physical therapy if > 20 degrees
- surgery if > 50 degrees
- estrogen has been tried in girls with scoliosis
- eye disorders
- dislocated lenses rarely require surgical removal
- patient should be monitored for retinal detachment
- endocarditis prophylaxis for mitral valve disorder
More general terms
References
- ↑ DeGowin & DeGowin's Diagnostic Examination, 6th edition, RL DeGowin (ed), McGraw Hill, NY 1994, pg 909
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, 2192-93
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 757
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1038, 2115-16
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 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 - ↑ 6.0 6.1 Stout M. The Marfan syndrome: implications for athletes and their echocardiographic assessment. Echocardiography. 2009 Oct;26(9):1075-81. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19840071
- ↑ Judge DP, Dietz HC. Marfan's syndrome. Lancet. 2005 Dec 3;366(9501):1965-76. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16325700
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/18328988
- ↑ 9.0 9.1 9.2 Lacro RV et al. Atenolol versus losartan in children and young adults with Marfan's syndrome. N Engl J Med 2014 Nov 18 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25405392 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1404731
- ↑ Dean JC Marfan syndrome: clinical diagnosis and management. Eur J Hum Genet. 2007 Jul;15(7):724-33. Epub 2007 May 9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17487218
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/22133496
- ↑ National Heart, Lung, and Blood Institute (NHLBI) Marfan Syndrome https://www.nhlbi.nih.gov/health-topics/marfan-syndrome
Patient information
Marfan syndrome patient information