Marfan's Syndrome

Author: Tracy Jones

Topic updated on 06/02/13 12:13pm

Introduction

A connective tissue disorder associated with
- long limbs
- skeletal abnormalities
- cardiovascular abnormalities
- ocular abnormalities
Epidemiology
- incidence
  - 1/10,000
- demographics
  - no ethnic or gender predilection known
Genetics
- autosomal dominant
  - mutation in fibrillin-1 (FBN1) gene
  - located on chromosome 15 (locus CH 15q21)
  - multiple mutations identified
Associated conditions
- orthopaedic conditions
  - arachnodactyly
  - scoliosis (50%)
  - protrusio acetabuli (15-25%)
  - ligamentous laxity
  - recurrent dislocations (patella, shoulder, fingers)
  - pes planovalgus
- nonorthopaedic conditions
  - cardiac abnormalities
    - aortic root dilatation
    - possible aortic dissection in future
    - mitral valve prolapse
  - superior lens dislocations (60%)
  - pectus excavatum
  - spontaneous pneumonthoraces
  - dural ectasia (>60%)
  - meningocele

Presentation

History
- scoliosis is usually the first to be diagnosed
- may be a history of ankle sprains secondary to ligamentous laxity
Symptoms
- asymptomatic in most cases
Physical exam
- dolichostenomelia (arm span greater than height (>1.05 ratio)
- arachnodactyly (long, thin toes and fingers)
- ligamentous hyperlaxity
- scoliosis

Imaging

Radiographs
- recommended
  - scoliosis series of spine
- findings
  - scoliosis
  - kyphosis
MRI
- MRI of spine prior to surgery
  - look for dural ectasia
Cardiac studies
- cardiac evaluation prior to surgery
  - cardiac consult
  - echocardiogram

Treatment

Scoliosis
- nonoperative
  - bracing
    - indications
      - early treatment of mild curve
    - outcomes
      - ineffective in most cases
- operative
  - ASF +/- PSF with instrumentation
    - indications
      - rapidly progressing curve in a skeletally immature patient
      - large curve in a skeletally mature patient
    - outcomes
      - higher complication rate than idiopathic scoliosis surgery
Acetabular protrusio
- nonoperative
  - observation unless severe symptoms develop
Joint laxity
- nonoperative
  - observation and orthotics as indicated

Complications

Postopertive Complications for Scoliosis Surgery
- 10-20% incidence following scoliosis surgery
- Infection, failure of instrumentation, pseudarthrosis, or decompensation of curve

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Qbank (4 Questions)

TAG

(OBQ12.88) Which of the following clinical or radiographic manifestations (Figures A-E) is most consistently linked with a mutation in the FBN1 gene? Topic

Review Topic

FIGURES: A

1. Figure A
2. Figure B
3. Figure C
4. Figure D
5. Figure E

PREFERRED RESPONSE ▶

DISCUSSION: Figure B shows dural ectasia, which is a classic manifestation of Marfan's syndrome. Marfan's syndrome is thought to be caused by a genetic mutation in the FBN1 gene (fibrillin-1).

Marfan's syndrome is an autosomal dominant condition caused by a mutation in the FBN1 gene. Orthopaedic manifestations of the condition include dural ectasia, scoliosis, protrusio acetabuli, ligamentous laxity, and pes planovalgus.

Loeys et al. present a revised Ghent nosology for the diagnosis of Marfan's syndrome. Their two main cardinal manifestations include aortic root aneurysm and ectopia lentis. No genetic testing is necessary to confirm the diagnosis if both are present. If one or none are present, the presence of the FBN1 mutation or a combination of systemic manifestations is necessary to make the diagnosis.

Shirley et al. report the musculoskeletal manifestations of Marfan's syndrome include scoliosis, dural ectasia, protrusio acetabuli, and ligamentous laxity. They also describe how the FBN1 gene is located on chromosome 15 and the gene mutation is present in >90% of patients with Marfan's.

Figure B is an axial cut from a T2-weighted MRI showing dural ectasia, or "ballooning" of the dural sac.

Incorrect Answers:
Answer 1: Figure A is a clinical photo showing an elevated scapula characteristic of Sprengel's deformity. Sprengel's deformity is not associated with the FBN1 gene.
Answer 3: Figure C shows a lateral radiograph in a child with sacral agenesis. Sacral agenesis is not associated with the FBN1 gene.
Answer 4: Figure D shows a radiograph of fibular hemimelia. Fibular hemimelia has been linked to the sonic hedge-hog gene.
Answer 5: Figure E is a clinical photo showing Lisch nodules, benign pigmented hamartomas of the iris, both consistent with neurofibromatosis. Neurofibromatosis is linked to the NF1 gene.

REFERENCES:

1. Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, Hilhorst-Hofstee Y, Jondeau G, Faivre L, Milewicz DM, Pyeritz RE, Sponseller PD, Wordsworth P, De Paepe AM. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010 Jul;47(7):476-85 PMID:20591885 (Link to Abstract)

2. Shirley ED, Sponseller PD. Marfan syndrome. J Am Acad Orthop Surg. 2009 Sep;17(9):572-81 PMID:19726741 (Link to Abstract)

Question Authors:

Mark Karadsheh MD, Derek Moore, Eric Shirley MD,

Please Rate Educational Value!

4.0

Average 4.0 of 3 Ratings

TAG

(OBQ10.118) All of the following are associated with Marfan's Syndrome EXCEPT? Topic

Review Topic

1. Dural ectasia
2. Inferior lens dislocation
3. Acetabular protrusio
4. Pectus excavatum
5. Dolichostenomelia

PREFERRED RESPONSE ▶

DISCUSSION: All of the following conditions, EXCEPT for Inferior lens dislocation, are associated with Marfan's Syndrome.

Inferior lens dislocation is associated with homocystinuria while superior lens dislocation is associated with Marfan syndrome. Dural ectasia is common in both Marfan syndrome and neurofibromatosis and can complicate spinal instrumentation. Acetabular protrusio, defined by center-edge angle greater than 40 degrees and medialization of the medial wall of the acetabulum past the ilioischial line or other definitions, and pectus excavatum are known musculoskeletal complications of Marfan syndrome. Dolichostenomelia is the medical condition of elongated limbs, like that seen in Marfan syndrome.

McBride et al. review the diagnosis, pathophysiology, and treatment options for acetabular protrusio.

Sponseller et al. performed a cross-sectional study on a cohort of 173 patients with Marfan syndrome to determine the prevalence and associated functionality of the hip in these patients. While patients with Marfan syndrome and acetabular protrusio have decreased hip range of motion, they are not significantly limited in their function and as such, the authors do not recommend prophylactic intervention.

REFERENCES:

1. McBride MT, Muldoon MP, Santore RF, Trousdale RT, Wenger DR. Protrusio acetabuli: diagnosis and treatment. J Am Acad Orthop Surg. 2001 Mar-Apr;9(2):79-88. Review. PMID:11281632 (Link to Abstract)

2. Sponseller PD, Jones KB, Ahn NU, Erkula G, Foran JR, Dietz HC 3rd. Protrusio acetabuli in Marfan syndrome: age-related prevalence and associated hip function. J Bone Joint Surg Am. 2006 Mar;88(3):486-95. PMID:16510812 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD, Eric Shirley MD,

Please Rate Educational Value!

2.0

Average 2.0 of 21 Ratings

TAG

(OBQ09.149) Marfan syndrome is an autosomal dominant disorder which results from a defective gene encoding for: Topic

Review Topic

1. Elastin
2. Fibrillin
3. Fibroblast Growth Factor Receptor 3 (FGFR3)
4. Collagen type 1
5. Collagen type 2

PREFERRED RESPONSE ▶

DISCUSSION: Marfan Syndrome is an autosomal dominant connective tissue disorder caused by a mutation in the gene encoding for fibrillin. Fibillin is a glycoprotein common in many tissues which is a structural component of elastin-containing microfibrils.

Marfan Syndrome is characterized by individuals with long, thin limbs, myopia, dural ectasia, and ectopia lentis. Associated medical conditions include cardiac abnormalities (mitral valve prolapse) and superior lens dislocations. Orthopaedic conditions include but are not limited to arachnodactyly, scoliosis, and ligamentous laxity.

Sponseller et al performed a study with the goals of determining the prevalence of current diagnostic findings in Marfan Syndrome. They found physical features with the highest diagnostic yield were craniofacial characteristics, thumb and wrist signs, pectus excavatum, and severe hindfoot valgus. They recommend patients with three to four physically evident features, or two highly specific features (e.g., thumb and wrist signs, craniofacial features, dural ectasia, or protrusio), should be carefully reexamined and possibly referred for an echocardiogram or a genetics consultation.

Shirley and Sponseller reviewed the diagnosis and treatment of Marfan syndrome. They report "compared to with patients with idiopathic scoliosis, patients with Marfan syndrome tend to have scoliosis that progresses at a faster rate and is more resistant to bracing; undergo scoliosis surgery complicated by greater blood loss, pseudarthrosis, and additional curvature; and have more frequent occurrences of dural ectasia, which may cause headaches, leg pain, or perineal pain."

Incorrect Answers:
Answer 1: A defect in Elastin is associated with supravalvular aortic stenosis (SVAS)and autosomal dominant cutis laxa.
Answer 3: A defect in FGFR3 is associated with Achondroplasia.
Answer 4: A defect in Type 1 collagen is associated with Osteogenesis Imperfecta and Ehlers Danlos syndrome
Answer 5: A defect in Collagen Type 2 is associated with SED, Achondrogenesis, Stickler Syndrome.

REFERENCES:

1. Sponseller PD, Erkula G, Skolasky RL, Venuti KD, Dietz HC 3rd. Improving clinical recognition of Marfan syndrome. J Bone Joint Surg Am. 2010 Aug 4;92(9):1868-75. PubMed PMID: 20686061. PMID: 20686061 (Link to Abstract)

2. Shirley ED, Sponseller PD. Marfan syndrome. J Am Acad Orthop Surg. 2009 Sep;17(9):572-81. Review. PubMed PMID: 19726741. PMID:19726741 (Link to Abstract)

Question Authors:

Derek Moore, Derek Moore, Eric Shirley MD,

Please Rate Educational Value!

3.0

Average 3.0 of 13 Ratings

TAG

(OBQ09.238) All of the following are true regarding treatment of scoliosis in patients with Marfan's syndrome EXCEPT? Topic

Review Topic

1. Bracing is often effective if started early enough
2. The cardiopulmonary condition of patients with Marfan syndrome should be evaluated and planned for before surgery
3. Preoperative computed tomograph should be performed to assess bony adequacy for fixation
4. Preoperative magnetic resonance imaging should be performed to evaluate for dural ectasia
5. There is an increased rate of pseudarthrosis post-operatively compared to adolescent idiopathic scoliosis

PREFERRED RESPONSE ▶

DISCUSSION: Spinal deformities are common in patients with Marfan syndrome and are usually refractory to conservative management.

Jones et al. (2007) review the treatment updates suggested during the symposium on the treatment of musculoskeletal aspects of Marfan syndrome. Specific to the spine, they review the types of spine deformity, treatment methods, anatomic considerations prior to surgery (e.g. dural ectasia), and operative complications. Preoperative evaluation of cardiopulmonary condition, bony adequacy, and dural ectasia are all indicated.

Jones et al. (2002) reviewed their treatment of 39 patients with Marfan syndrome treated with instrumented spinal fusion for scoliosis or kyphosis. They found increased blood loss, post-operative infection, dural tear, instrumentation fixation failure, pseudarthrosis, and curve decompensation.

REFERENCES:

1. Jones KB, Sponseller PD, Erkula G, Sakai L, Ramirez F, Dietz HC 3rd, Kost-Byerly S, Bridwell KH, Sandell L. Symposium on the musculoskeletal aspects of Marfan syndrome: meeting report and state of the science. J Orthop Res. 2007 Mar;25(3):413-22. PMID:17143900 (Link to Abstract)

2. Jones KB, Erkula G, Sponseller PD, Dormans JP. Spine deformity correction in Marfan syndrome. Spine (Phila Pa 1976). 2002 Sep 15;27(18):2003-12. PMID:12634560 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD, Eric Shirley MD, Derek Moore,

Please Rate Educational Value!

3.0

Average 3.0 of 5 Ratings

Posts

Spine deformity correction in Marfan syndrome. Includes Poll

Jones KB, Erkula G, Sponseller PD, Dormans JP
Spine. 2002 Sep;27(18):2003-12. PMID: 12634560 (Link to Pubmed)

Spine - Journal Club - Marfan's Syndrome

4/22/2013

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ABOS II: Marfan's Syndrome

General - Oral Boards Review

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Evidence & References Show References

Level of Evidence 4 (Case Series)

Jones KB, Erkula G, Sponseller PD, Dormans JP. Spine deformity correction in Marfan syndrome. Spine (Phila Pa 1976). 2002 Sep 15;27(18):2003-12. PMID:12634560 (Link to Abstract)

Level of Evidence 5 and Other Journal Articles (includes Case Reports, Expert Opinions, Personal Observations, and Biomechanic Studies)

Jones KB, Sponseller PD, Erkula G, Sakai L, Ramirez F, Dietz HC 3rd, Kost-Byerly S, Bridwell KH, Sandell L. Symposium on the musculoskeletal aspects of Marfan syndrome: meeting report and state of the science. J Orthop Res. 2007 Mar;25(3):413-22. PMID:17143900 (Link to Abstract)
Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, Hilhorst-Hofstee Y, Jondeau G, Faivre L, Milewicz DM, Pyeritz RE, Sponseller PD, Wordsworth P, De Paepe AM. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010 Jul;47(7):476-85 PMID:20591885 (Link to Abstract)
McBride MT, Muldoon MP, Santore RF, Trousdale RT, Wenger DR. Protrusio acetabuli: diagnosis and treatment. J Am Acad Orthop Surg. 2001 Mar-Apr;9(2):79-88. Review. PMID:11281632 (Link to Abstract)
Shirley ED, Sponseller PD. Marfan syndrome. J Am Acad Orthop Surg. 2009 Sep;17(9):572-81 PMID:19726741 (Link to Abstract)
Sponseller PD, Jones KB, Ahn NU, Erkula G, Foran JR, Dietz HC 3rd. Protrusio acetabuli in Marfan syndrome: age-related prevalence and associated hip function. J Bone Joint Surg Am. 2006 Mar;88(3):486-95. PMID:16510812 (Link to Abstract)

Textbooks

Review of Orthopaedics, 6th Edition, Mark D. Miller MD, Stephen R. Thompson MBBS MEd FRCSC, Jennifer Hart MPAS PA-C ATC, an imprint of Elsevier, Philadelphia, Copyright 2012
AAOS Comprehensive Orthopaedic Review, Jay R. Leiberman. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2009
Orthopaedic Knowledge Update 10, John M Flyn. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2011
Hoppenfeld SP. Surgical Exposures in Orthopaedics: The Anatomic Approach. Lipponcott, Williams, and Wilkins, Philadelphia, PA, Copyright 2009
Orthopaedic In-training Examination (OITE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012
Self-Assessment Examination (SAE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012

Undefined

Shirley ED, Sponseller PD. Marfan syndrome. J Am Acad Orthop Surg. 2009 Sep;17(9):572-81. Review. PubMed PMID: 19726741. PMID:19726741 (Link to Abstract)
Sponseller PD, Erkula G, Skolasky RL, Venuti KD, Dietz HC 3rd. Improving clinical recognition of Marfan syndrome. J Bone Joint Surg Am. 2010 Aug 4;92(9):1868-75. PubMed PMID: 20686061. PMID: 20686061 (Link to Abstract)

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Marfan's Syndrome

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