Marfan’s Syndrome Bradley K. Harrison, MD

How do we diagnose the Marfan syndrome? Recognition of both “major” and “minor” clinical manifestations involving: Skeletal Cardiovascular Ocular manifestations Dura/other Two systems, including one major should be involved

Skeletal findings Major (need 4) Reduced upper to lower segment ratio Arm span exceeding height Arachnodactly of fingers and toes with positive wrist and thumb signs Scoliosis >20% or spondylolisthesis Pectus carinatum Pectus excavatum requiring surgery Reduced extension of elbows (<170°) Medial displacement of medial malleolus causing pes planus Protrusio acetabulea

Skeletal findings: Major Reduced upper to lower segment ratio Arm span exceeding height

Skeletal findings: Major Arachnodactly of fingers and toes with positive wrist and thumb signs Thumb sign: distal phalanx protrudes beyond border of clenched fist Wrist sign: thumb and 5th digit overlap

Skeletal findings: Major Scoliosis >20% Spondylolisthesis Pectus carinatum Pectus excavatum requiring surgery Reduced extension of elbows (<170°)

Skeletal findings continued Minor Pectus excavatum of moderate severity Joint hypermobility High arched palate with crowding of teeth Facial features Dolichocephaly Malar hypoplasia Enopthalmos Retrognathia Down-slanting palpebral fissures

Skeletal findings: Minor High arched palate with crowding of teeth Dolichocephaly Retrognathia

Cardiovascular findings Major (need 1) Dilitation of the ascending aorta involving the sinuses of Valsalva, with or without aortic regurgitation Dissecting of the ascending aorta

Cardiovascular findings: Major Dilitation of the ascending aorta

Cardiovascular findings continued Minor Mitral valve prolapse Mitral regurgitation Dilitation of the pulmonary artery, in the absence of valvular or peripheral pulmonic stenosis, below age 40 Calcification of mitral annulus below age 40 Dilatation or dissection of descending thoracic or abdominal aorta below age 50

Ocular findings Major Minor Ectopia lentis (typically upward) Flat cornea (measured by keratometry) Increased axial globe length (u/s) Hypoplastic iris or hypoplastic ciliary muscle causing decreased miosis Myopia Retinal detachment

Other findings Major Minor Dural ectasia affecting the lumbosacral spinal canal Minor Spontaneous pneumothorax Apical blebs Cutaneous striae distensae Recurrent or incisional hernias

History of the Marfan syndrome 1896: A.B. Marfan described 5 y/o female with long thin legs he characterized as “spider-like” 1914: dislocated lenses 1931: autosomal dominant inheritence 1943: aneurysm of the ascending aorta 1955: comprehensive Marfan’s syndrome 1968: aortic-root replacement

The Marfan Syndrome (MFS) Most common inherited disorder of connective tissue (2-3 per 10,000) Autosomal dominant Fibrillin-1 gene (FBN1) located on chromosome 15q21 75% inherited, 25% de novo mutation FBN1 penetrance high Phenotypic expression is extremely variable Without a particular gender, racial, geographic, or ethnic predilection

MFS continued Differential Diagnosis Homocystinuria: Marfanoid habitus, ectopia lentis, mental retardation, osteoporosis Serum amino acid analysis MASS phenotype: Mitral valve prolapse, mild aortic dilatiation, striae atrophica, skeletal involvement Ehlers-Danlos syndrome: marked joint hypermobility, paparaceous scars, mitral prolapse Stickler’s syndrome: tall stature, retrognathia, mitral valve prolapse, midfacial hypoplasia, retinal detachment Beil’s syndrome (congenital contractural arachnodactly): arachnodactly, joint contractures, scoliosis, crumpled ear malformation

MFS continued Management Annual echocardiogram: size and function of heart and aorta Β-adrenergic blocker: shown to slow progressive widening of the aorta Aortic root replacement: indicated when aortic root diameter >50-55mm Annual ophthalmologic examination: screening for strabismus, myopia, lens dislocation Lifestyle adaptations, restriction of physical activity (4-6 METS), avoidance of competitive sports and weight training Pregnancy: Β-adrenergic blocker, >40mm @ risk, >50mm elective repair, epidural, C-section