Marfans Syndrome Bradley K Harrison MD How do

Marfan’s Syndrome Bradley K. Harrison, MD

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

Skeletal findings ¡ Major (need 4) l l l l l 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 5 th digit overlap

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

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

Ocular findings ¡ Major l ¡ Ectopia lentis (typically upward) Minor l l l 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 l ¡ Dural ectasia affecting the lumbosacral spinal canal Minor l l 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 l l l ¡ Fibrillin-1 gene (FBN 1) located on chromosome 15 q 21 75% inherited, 25% de novo mutation FBN 1 penetrance high Phenotypic expression is extremely variable Without a particular gender, racial, geographic, or ethnic predilection

MFS continued ¡ Differential Diagnosis l Homocystinuria: Marfanoid habitus, ectopia lentis, mental retardation, osteoporosis ¡ l l 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 l l l 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 -55 mm 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, >40 mm @ risk, >50 mm elective repair, epidural, C-section