Marfan Marfan Syndrome Syndrome

Stephanie van Colen, DOStephanie van Colen, DO

Marfan SyndromeMarfan Syndrome

Marfan syndrome is an inherited Marfan syndrome is an inherited connective tissue disorder connective tissue disorder

Autosomal dominant Autosomal dominant Results from molecular defects in the Results from molecular defects in the

fibrillin genefibrillin gene, (FBN1) on chromosome , (FBN1) on chromosome 15 (q15-q21)15 (q15-q21)

Impaired structural integrity of the Impaired structural integrity of the skeletal, ocular, and cardiovascular skeletal, ocular, and cardiovascular systems systems

FeaturesFeatures

Tall statureTall stature Mitral-valve prolapseMitral-valve prolapse Aortic-root dilatationAortic-root dilatation Aortic dissectionAortic dissection Pectus deformitiesPectus deformities Occular problems - ectopia lentisOccular problems - ectopia lentis Joint laxityJoint laxity Spinal deformitiesSpinal deformities

PathophisiologyPathophisiology

The affected gene encodes for the The affected gene encodes for the glycoprotein glycoprotein fibrillinfibrillin: a major : a major building block of microfibrilsbuilding block of microfibrils - - structural components of the structural components of the suspensory suspensory ligament of the lens ligament of the lens - - elastin in the aorta and other elastin in the aorta and other connective connective tissuestissues

PathophysiologyPathophysiology

Abnormalities in the microfibrils Abnormalities in the microfibrils - weaken the aortic wall- weaken the aortic wall Progressive aortic dilatation and Progressive aortic dilatation and

possible aortic dissection secondary to possible aortic dissection secondary to tension caused by left ventricular tension caused by left ventricular ejection ejection

Deficient fibrillin - Deficient fibrillin - reduced structural integrity of the lens reduced structural integrity of the lens zonules, ligaments, lung airways, and zonules, ligaments, lung airways, and spinal dura spinal dura

In patients with Marfan’s, the media is affected and

has decreased tensile strength

Physical FindingsPhysical Findings

The diagnosis of Marfan syndrome is The diagnosis of Marfan syndrome is mainly clinical mainly clinical

Skeletal findingsSkeletal findings Taller/thinner statureTaller/thinner stature Limbs are disproportionately long Limbs are disproportionately long

compared with the trunk compared with the trunk (dolichostenomelia)(dolichostenomelia)

ArachnodactylyArachnodactyly

Physical FindingsPhysical Findings Major criteriaMajor criteria include the following: include the following:

Pectus excavatum (severe)/ pectus carinatum Pectus excavatum (severe)/ pectus carinatum Reduced upper-to-lower body segment ratio Reduced upper-to-lower body segment ratio Arms and legs may be unusually long in proportion Arms and legs may be unusually long in proportion

to the torsoto the torso Positive wrist (Walker) and thumb (Steinberg) Positive wrist (Walker) and thumb (Steinberg)

signssigns Scoliosis greater than 20°: > 60% of patients Scoliosis greater than 20°: > 60% of patients Reduced extension of the elbows (<170°) Reduced extension of the elbows (<170°) Medial displacement of medial malleolus - pes Medial displacement of medial malleolus - pes

planus planus Protrusio acetabula of any degreeProtrusio acetabula of any degree

Positive wrist (Walker) sign

Positive thumb (Steinberg) sign

Physical FindingsPhysical Findings Minor criteriaMinor criteria are as follows: are as follows:

Pectus excavatum (moderate)Pectus excavatum (moderate) Scoliosis less than 20° Scoliosis less than 20° Thoracic lordosis Thoracic lordosis Joint hypermobility Joint hypermobility Highly arched palate Highly arched palate Dental crowding Dental crowding Typical facies (dolichocephaly, malar hypoplasia, Typical facies (dolichocephaly, malar hypoplasia,

enophthalmos, retrognathia, down-slanting enophthalmos, retrognathia, down-slanting palpebral fissures)palpebral fissures)

For the skeletal system to be involved, need 2 For the skeletal system to be involved, need 2 major criteria or 1 major criterion plus 2 minor major criteria or 1 major criterion plus 2 minor criteriacriteria

Other systemsOther systems Ocular findings:Ocular findings:

The major criterion is ectopia lentis; @ 50%The major criterion is ectopia lentis; @ 50% Multiple other ocular findingsMultiple other ocular findings

Pulmonary findings:Pulmonary findings: Minor criteria include the following: Minor criteria include the following:

Spontaneous pneumothorax (about 5%) Spontaneous pneumothorax (about 5%) Apical blebsApical blebs

Dural findings:Dural findings: 1 major criterion is defined: Dural ectasia (seen on CT / 1 major criterion is defined: Dural ectasia (seen on CT /

MRI)MRI) Seen in 65-92%, usually in the lumbosacral spineSeen in 65-92%, usually in the lumbosacral spine Dural ectasia: ballooning / widening of the dural sac +/- Dural ectasia: ballooning / widening of the dural sac +/-

herniation of the nerve root sleeves out of the foraminaherniation of the nerve root sleeves out of the foramina Less than 20% of patients have serious dural ectasiaLess than 20% of patients have serious dural ectasia

CardiovascularCardiovascular Major criteriaMajor criteria: :

Aortic-root dilatation: ( 70-80%) Aortic-root dilatation: ( 70-80%) Aortic dissections involving the ascending aortaAortic dissections involving the ascending aorta

Minor criteriaMinor criteria: : Mitral valve prolapse (55-69%)Mitral valve prolapse (55-69%) Dilatation of proximal main pulmonary artery Dilatation of proximal main pulmonary artery

without pulmonic stenosis or other cause without pulmonic stenosis or other cause Calcification of mitral annulus (patients <40 y) Calcification of mitral annulus (patients <40 y) Dilatation of abdominal or descending thoracic Dilatation of abdominal or descending thoracic

aorta (patients <50 y)aorta (patients <50 y) For the CV system to be involved, need 1 For the CV system to be involved, need 1

minor criterionminor criterion

Differential Differential

Ehlers-Danlos SyndromeEhlers-Danlos Syndrome Fragile X syndromeFragile X syndrome Gigantism and acromegalyGigantism and acromegaly HyperpituitarismHyperpituitarism HyperthyroidismHyperthyroidism Klinefelter syndromeKlinefelter syndrome

EchocardiographyEchocardiography

Diagnosis and management of aortic-root Diagnosis and management of aortic-root dilatationdilatationThe upper limit of the normal aortic root The upper limit of the normal aortic root size is 1.9 cm/m2 of body surface areasize is 1.9 cm/m2 of body surface area

Assesses mitral-valve prolapse, LV size / Assesses mitral-valve prolapse, LV size / function, LA size, and tricuspid valve function, LA size, and tricuspid valve functionfunction

TEE assesses the distal ascending and TEE assesses the distal ascending and descending aorta and prosthetic valvesdescending aorta and prosthetic valves

Doppler echocardiography - detecting and Doppler echocardiography - detecting and grading aortic and mitral regurgitationgrading aortic and mitral regurgitation

CT and MRICT and MRI

MRI for assessing chronic dissection of MRI for assessing chronic dissection of the aortathe aorta- any patient who has an aortic-root - any patient who has an aortic-root dimension >150% of the mean for their dimension >150% of the mean for their body surface area or body surface area or - ratio of actual to predicted aortic-root - ratio of actual to predicted aortic-root dimension >1.5dimension >1.5

CT or MRI of the lumbosacral spine to CT or MRI of the lumbosacral spine to evaluate for dural ectasiaevaluate for dural ectasia

TreatmentTreatment

Cardiovascular surgeryCardiovascular surgery CV surgery can substantially prolong CV surgery can substantially prolong

survival Prophylactic / emergency CV survival Prophylactic / emergency CV surgery is needed for:surgery is needed for:- aortic and mitral regurgitation - aortic and mitral regurgitation - aortic aneurysm- aortic aneurysm- aortic dissection- aortic dissection

In cases of acute proximal aortic In cases of acute proximal aortic dissection, emergency surgical dissection, emergency surgical replacement of the aortic root is performed replacement of the aortic root is performed

TreatmentTreatment

The ascending aorta is usually replaced The ascending aorta is usually replaced when the diameter exceeds 55-60 mmwhen the diameter exceeds 55-60 mm

Composite valve-graft replacement is Composite valve-graft replacement is performed performed - prosthetic valve sewn into a tube graft - prosthetic valve sewn into a tube graft with reimplantation of the coronary with reimplantation of the coronary ostia (modified Bentall procedure)ostia (modified Bentall procedure)

Low rates of morbidity and mortalityLow rates of morbidity and mortality

Bentall procedureBentall procedure Repair of Type A aortic dissection, aneurysm Repair of Type A aortic dissection, aneurysm

of the proximal ascending aorta, and of the proximal ascending aorta, and aortoannular ectasiaaortoannular ectasia

Replacement of the root and proximal Replacement of the root and proximal ascending aorta with a tube graft containing a ascending aorta with a tube graft containing a prosthetic valve and reimplantation of the prosthetic valve and reimplantation of the coronary arteries into the graft coronary arteries into the graft

Postoperative complications include:Postoperative complications include: leakage at the suture lines - pseudoaneurysm of the leakage at the suture lines - pseudoaneurysm of the

aortic or coronary anastomosisaortic or coronary anastomosis

TreatmentTreatment

Non-cardiac TreatmentNon-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

Medical ManagementMedical Management

Beta-blockersBeta-blockers May delay aortic dilatation and May delay aortic dilatation and

progression to rupture or dissection. progression to rupture or dissection. The rate of surgical interventions has The rate of surgical interventions has

substantially declined during the past substantially declined during the past decade of beta-blockade use. decade of beta-blockade use.

Medical TreatmentMedical Treatment

Anticoagulants are needed after Anticoagulants are needed after artificial artificial heart-valve placement heart-valve placement

IV antibiotic therapy is required during IV antibiotic therapy is required during cardiac and noncardiac procedures to cardiac and noncardiac procedures to prevent bacterial endocarditisprevent bacterial endocarditis

Progesterone and estrogen therapy Progesterone and estrogen therapy have been used to induce puberty and have been used to induce puberty and reduce the patient's ultimate height - reduce the patient's ultimate height - if tx is begun before pubertyif tx is begun before puberty

ReferrencesReferrences

Caffey’s Pediatric Diagnostic ImagingCaffey’s Pediatric Diagnostic Imaging, , Vol. 2, Kuhn, Slovis and Haller, Mosby, Vol. 2, Kuhn, Slovis and Haller, Mosby, 2004.2004.

Thoracic Imaging,Thoracic Imaging, Webb, R. and Higgins, Webb, R. and Higgins, C., Lippincott Williams & Wilkins, 2005.C., Lippincott Williams & Wilkins, 2005.

emedicine.comemedicine.com mayoclinic.orgmayoclinic.org marfan.orgmarfan.org