55 Marfan Syndrome
Marfan Syndrome 741
MFS
Dolichostenomelia, ectopia lentis, dilatation/dissec- tion of the ascending aorta, lumbosacral dural ectasia Frequency: 1 in 10,000 births.
Genetics
Autosomal dominant (OMIM 154700) with high pen- etrance, due to mutation in the fibrillin 1 (FBN1) gene mapped to 15q21.1; one fourth represent new mutations, paternal age effect; allelic to Shprintzen- Goldberg syndrome, autosomal dominant Weill- Marchesani syndrome, the MASS phenotype, iso- lated ectopia lentis, and isolated aortic aneurysm.
A second locus mapped to 3p24.2-25, the disease gene being TGF-beta receptor 2.
Clinical Features
• Tall, thin body habitus, winging of scapulae, dolichostenomelia
• Dolichocephaly, prominent supraorbital ridges
• Myopia, upward ectopia lentis, retinal detachment
• High-arched palate
• Pectus excavatum/carinatum
• Scoliosis, kyphoscoliosis, lordosis
• Aortic root dilatation, aortic regurgitation, aortic aneurysm, aortic dissection
• Mitral valve prolapse, mitral regurgitation
• Arachnodactyly, camptodactyly of 5th fingers, joint laxity
• Pes planus
• Inguinal hernia Differential Diagnosis
• Homocystinuria
• Congenital contractural arachnodactyly
• Weill-Marchesani syndrome
• MASS phenotype
• Stickler syndrome
Radiographic Features Skull
• Dolichocephaly
• Enlarged paranasal (maxillary) sinuses
• Mandibular prognathism Spine
• Kyphoscoliosis
• Spondylolisthesis
• Atlanto-axial instability, laxity of lumbar vertebral joints
• Increased interpediculate space distance, enlarged vertebrae
• Sacral meningocele Hands and Feet
• Elongation of tubular bones in hands and feet
• High metacarpal index (ratio of length to width)
• Flexion deformities
• Disproportionate elongation of the great toe, hallux valgus
• Clubfoot, pes planus
• Calcaneal enthesophytes Joints
• Joint instability, multiple joint dislocations (1st metacarpal-phalangeal, sternoclavicular, hip, pa- tella, mandible, perilunate)
• Premature osteoarthritis Limbs
• Slender, gracile bones
• Marked diminution of soft tissue
• Limb length discrepancy
• Genu recurvatum
• Patella alta Pelvis
• Protrusio acetabuli
• Slipped capital femoral epiphysis Generalized Bone Defects
• Normal or advanced bone age Chest
• Pectus excavatum or carinatum
• Thin ribs
M
Bibliography
Aoyama T, Francke U, Gasner C, Furthmayr H. Fibrillin abnor- malities and prognosis in Marfan syndrome and related disorders. Am J Med Genet 1995; 58: 169–76
De Paepe A, Devereux RB, Dietz HC, Hennekam RCM, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome.
Am J Med Genet 1996; 62: 417–26
Gray JR.A clinical severity grading scale for Marfan syndrome.
J Med Genet 1996; 33: 758–9
Gray JR, Davies SJ. Marfan syndrome. J Med Genet 1996; 33:
403–8
McKusick VA. Heritable disorders of connective tissue. C.V.
Mosby Company, St. Louis, 1972 (4th ed.)
Mizuguchi T, Collod-Beroud G, Akiyama T, Abifadel M, Hara- da N, Morisaki T, Allard D, Varret M, Claustres M, Morisaki H, Ihara M, Kinoshita A, Yoshiura K, Junien C, Kajii T, Jondeau G, Ohta T, Kishino T, Furukawa Y, Nakamura Y, Niikawa N, Boileau C, Matsumoto N. Heterozygous TGFBR2 mutations in Marfan syndrome. Nat Genet. 2004; 36: 855–60
Montgomery RA, Geraghty MT, Bull E, Gelb BD, Johnson M, McIntosh I, Francomano CA, Dietz HC. Multiple molecular mechanisms underlying subdiagnostic variants of Marfan syndrome. Am J Hum Genet 1998; 63: 1703–11
Morse RP, Rockenmacher S, Pyeritz RE, Sanders SP, Bieber FR, Lin A, MacLeod P, Hall B, Graham JM. Diagnosis and man- agement of infantile Marfan syndrome. Pediatrics 1990; 86:
888–95
Pyeritz RE. The Marfan syndrome. In: Royce PM, Steinmann B (eds.) Connective tissue and its heritable disorders: molec- ular, genetic, and medical aspects. Wiley-Liss, New York, 1993, pp. 437–68
Silverman DI, Burton KJ, Gray J, Bosner MS, Kouchoukos NT, Roman MJ, Boxer M, Devereux RB, Tsipouras P. Life ex- pectancy in the Marfan syndrome. Am J Cardiol 1995; 75:
157–60
Sponseller PD, Hobbs W, Riley LH, Pyeritz RE. The thora- columbar spine in Marfan syndrome. J Bone Joint Surg Am 1995; 77: 867–76
Marfan Syndrome 742
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)
a
b
c
Marfan Syndrome 743
M
Fig. 55.2. Patient 2, adult. Note elongated clavicles and ribs and mild thoracic scoliosis
Fig. 55.3. Patient 2, adult. Slender long bones, with diminution of surrounding soft tissues
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
a b
