1. Marfan Syndrome
Stephanie van Colen, DO

2. Marfan Syndrome
Marfan syndrome is an inherited connective tissue disorder
Autosomal dominant
Results from molecular defects in the fibrillin gene, (FBN1) on chromosome 15 (q15-q21)
Impaired structural integrity of the skeletal, ocular, and cardiovascular systems

3. Features Tall stature Mitral-valve prolapse Aortic-root dilatation
Aortic dissection
Pectus deformities
Occular problems - ectopia lentis
Joint laxity
Spinal deformities

4. Pathophisiology
The affected gene encodes for the glycoprotein fibrillin: a major building block of microfibrils - structural components of the suspensory ligament of the lens elastin in the aorta and other connective tissues

5. Pathophysiology
Abnormalities in the microfibrils - weaken the aortic wall
Progressive aortic dilatation and possible aortic dissection secondary to tension caused by left ventricular ejection
Deficient fibrillin - reduced structural integrity of the lens zonules, ligaments, lung airways, and spinal dura

6. In patients with Marfan’s, the media is affected and has decreased tensile strength

7. Physical Findings The diagnosis of Marfan syndrome is mainly clinical
Skeletal findings
Taller/thinner stature
Limbs are disproportionately long compared with the trunk (dolichostenomelia)
Arachnodactyly

8. Physical Findings Major criteria include the following:
Pectus excavatum (severe)/ pectus carinatum
Reduced upper-to-lower body segment ratio
Arms and legs may be unusually long in proportion to the torso
Positive wrist (Walker) and thumb (Steinberg) signs
Scoliosis greater than 20°: > 60% of patients
Reduced extension of the elbows (<170°)
Medial displacement of medial malleolus - pes planus
Protrusio acetabula of any degree

9. Positive thumb (Steinberg) sign
Positive wrist (Walker) sign

11. Physical Findings Minor criteria are as follows:
Pectus excavatum (moderate)
Scoliosis less than 20°
Thoracic lordosis
Joint hypermobility
Highly arched palate
Dental crowding
Typical facies (dolichocephaly, malar hypoplasia, enophthalmos, retrognathia, down-slanting palpebral fissures)
For the skeletal system to be involved, need 2 major criteria or 1 major criterion plus 2 minor criteria

12. Other systems Ocular findings: Pulmonary findings: Dural findings:
The major criterion is ectopia 50%
Multiple other ocular findings
Pulmonary findings:
Minor criteria include the following:
Spontaneous pneumothorax (about 5%)
Apical blebs
Dural findings:
1 major criterion is defined: Dural ectasia (seen on CT / MRI)
Seen in 65-92%, usually in the lumbosacral spine
Dural ectasia: ballooning / widening of the dural sac +/- herniation of the nerve root sleeves out of the foramina
Less than 20% of patients have serious dural ectasia

13. Cardiovascular Major criteria: Minor criteria:
Aortic-root dilatation: ( 70-80%)
Aortic dissections involving the ascending aorta
Minor criteria:
Mitral valve prolapse (55-69%)
Dilatation of proximal main pulmonary artery without pulmonic stenosis or other cause
Calcification of mitral annulus (patients <40 y)
Dilatation of abdominal or descending thoracic aorta (patients <50 y)
For the CV system to be involved, need 1 minor criterion

17. Differential Ehlers-Danlos Syndrome Fragile X syndrome
Gigantism and acromegaly
Hyperpituitarism
Hyperthyroidism
Klinefelter syndrome

18. Echocardiography
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
Assesses mitral-valve prolapse, LV size / function, LA size, and tricuspid valve function
TEE assesses the distal ascending and descending aorta and prosthetic valves
Doppler echocardiography - detecting and grading aortic and mitral regurgitation

19. CT and MRI
MRI for assessing chronic dissection of the aorta - any patient who has an aortic-root dimension >150% of the mean for their body surface area or - ratio of actual to predicted aortic-root dimension >1.5
CT or MRI of the lumbosacral spine to evaluate for dural ectasia

20. Treatment Cardiovascular surgery
CV surgery can substantially prolong survival Prophylactic / emergency CV surgery is needed for: - aortic and mitral regurgitation - aortic aneurysm - aortic dissection
In cases of acute proximal aortic dissection, emergency surgical replacement of the aortic root is performed

21. Treatment
The ascending aorta is usually replaced when the diameter exceeds mm
Composite valve-graft replacement is performed - prosthetic valve sewn into a tube graft with reimplantation of the coronary ostia (modified Bentall procedure)
Low rates of morbidity and mortality

22. Treatment Bentall procedure
Repair of Type A aortic dissection, aneurysm of the proximal ascending aorta, and aortoannular ectasia
Replacement of the root and proximal ascending aorta with a tube graft containing a prosthetic valve and reimplantation of the coronary arteries into the graft
Postoperative complications include:
leakage at the suture lines - pseudoaneurysm of the aortic or coronary anastomosis

23. Non-cardiac Treatment
Scoliosis surgery
Pectus repair
Repair of pectus excavatum to improve respiratory mechanics
Pectus carinatum repair - mainly for cosmetic reasons
Pneumothorax therapy
Ocular therapy
Medical management

24. Medical Management Beta-blockers
May delay aortic dilatation and progression to rupture or dissection.
The rate of surgical interventions has substantially declined during the past decade of beta-blockade use.

25. Medical Treatment
Anticoagulants are needed after artificial heart-valve placement
IV 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 tx is begun before puberty

26. Referrences
Caffey’s Pediatric Diagnostic Imaging, Vol. 2, Kuhn, Slovis and Haller, Mosby, 2004.
Thoracic Imaging, Webb, R. and Higgins, C., Lippincott Williams & Wilkins, 2005.
emedicine.com
mayoclinic.org
marfan.org