Marfan Syndrome 741

55 Marfan Syndrome

MFS Radiographic Features Skull Dolichostenomelia, ectopia lentis, dilatation/dissec- • Dolichocephaly tion of the ascending aorta, lumbosacral dural ectasia • Enlarged paranasal (maxillary) sinuses • Mandibular prognathism Frequency: 1 in 10,000 births. Spine • Kyphoscoliosis Genetics • Spondylolisthesis Autosomal dominant (OMIM 154700) with high pen- • Atlanto-axial instability, laxity of lumbar vertebral etrance, due to mutation in the fibrillin 1 (FBN1) joints gene mapped to 15q21.1; one fourth represent new • Increased interpediculate space distance, enlarged mutations, paternal age effect; allelic to Shprintzen- vertebrae Goldberg syndrome, autosomal dominant Weill- • Sacral meningocele Marchesani syndrome, the MASS phenotype, iso- Hands and Feet lated ectopia lentis, and isolated aortic aneurysm. • Elongation of tubular bones in hands and feet A second locus mapped to 3p24.2-25, the disease • High metacarpal index (ratio of length to width) gene being TGF-beta receptor 2. • Flexion deformities • Disproportionate elongation of the great toe, Clinical Features hallux valgus • Tall, thin body habitus, winging of scapulae, • Clubfoot, pes planus dolichostenomelia • Calcaneal enthesophytes • Dolichocephaly, prominent supraorbital ridges Joints • Myopia, upward ectopia lentis, retinal detachment • Joint instability, multiple joint dislocations (1st • High-arched palate metacarpal-phalangeal, sternoclavicular, hip, pa- • Pectus excavatum/carinatum tella, mandible, perilunate) • Scoliosis, kyphoscoliosis, lordosis • Premature osteoarthritis • Aortic root dilatation, aortic regurgitation, aortic Limbs aneurysm, aortic dissection • Slender, gracile bones • Mitral valve prolapse, mitral regurgitation • Marked diminution of soft tissue • Arachnodactyly, camptodactyly of 5th fingers, • Limb length discrepancy M joint laxity • Genu recurvatum • Pes planus • Patella alta • Inguinal hernia Pelvis • Protrusio acetabuli Differential Diagnosis • Slipped capital femoral epiphysis • Homocystinuria Generalized Bone Defects • Congenital contractural arachnodactyly • Normal or advanced bone age • Weill-Marchesani syndrome Chest • MASS phenotype • Pectus excavatum or carinatum • Stickler syndrome • Thin ribs 742 Marfan Syndrome

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Fig. 55.1 a–c. Patient 1, age 14 years. a Dolichostenomelia, winging of scapulae, and scoliosis. b, c Arachnodactyly of fingers and toes. (From archive of Dr. P.Balestrazzi, University of Parma, Italy, with permission)

Bibliography Montgomery RA, Geraghty MT, Bull E, Gelb BD, Johnson M, McIntosh I, Francomano CA, Dietz HC. Multiple molecular Aoyama T,Francke U, Gasner C, Furthmayr H. Fibrillin abnor- mechanisms underlying subdiagnostic variants of Marfan malities and prognosis in Marfan syndrome and related syndrome. Am J Hum Genet 1998; 63: 1703–11 disorders. Am J Med Genet 1995; 58: 169–76 Morse RP,Rockenmacher S, Pyeritz RE, Sanders SP,Bieber FR, De Paepe A, Devereux RB, Dietz HC, Hennekam RCM, Pyeritz Lin A, MacLeod P,Hall B, Graham JM. Diagnosis and man- RE. Revised diagnostic criteria for the Marfan syndrome. agement of infantile Marfan syndrome. Pediatrics 1990; 86: Am J Med Genet 1996; 62: 417–26 888–95 Gray JR.A clinical severity grading scale for Marfan syndrome. Pyeritz RE. The Marfan syndrome. In: Royce PM, Steinmann B J Med Genet 1996; 33: 758–9 (eds.) Connective tissue and its heritable disorders: molec- Gray JR, Davies SJ. Marfan syndrome. J Med Genet 1996; 33: ular, genetic, and medical aspects. Wiley-Liss, New York, 403–8 1993, pp. 437–68 McKusick VA. Heritable disorders of connective tissue. C.V. Silverman DI, Burton KJ, Gray J, Bosner MS, Kouchoukos NT, Mosby Company, St. Louis, 1972 (4th ed.) Roman MJ, Boxer M, Devereux RB, Tsipouras P. Life ex- Mizuguchi T, Collod-Beroud G, Akiyama T, Abifadel M, Hara- pectancy in the Marfan syndrome. Am J Cardiol 1995; 75: da N, Morisaki T,Allard D,Varret M, Claustres M, Morisaki 157–60 H, Ihara M, Kinoshita A, Yoshiura K, Junien C, Kajii T, Sponseller PD, Hobbs W, Riley LH, Pyeritz RE. The thora- Jondeau G, Ohta T, Kishino T, Furukawa Y, Nakamura Y, columbar spine in Marfan syndrome. J Bone Joint Surg Am Niikawa N, Boileau C, Matsumoto N. Heterozygous TGFBR2 1995; 77: 867–76 mutations in Marfan syndrome.Nat Genet.2004; 36: 855–60 Marfan Syndrome 743

Fig. 55.2. Patient 2, adult. Note elongated clavicles and ribs Fig. 55.3. Patient 2, adult. Slender long bones, with diminution and mild thoracic scoliosis of surrounding soft tissues

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Fig. 55.4 a,b. Patient 2, adult. Tubular bones in hands and feet are elongated and gracile. Note 5th finger camptodactyly, dispro- portionate elongation of great toes, and bilateral hallux valgus