Marfan Syndrome

Introduction

On your exam of a new patient, a 12-year-old girl, you hear a diastolic murmur in left upper sternal border as well as a mid-systolic click with late systolic murmur. You also notice she has long, thin limbs and a positive thumb sign and wrist sign. What further evaluation would you perform? 

The above case is representative of Marfan's Syndrome, and given the incidence, it is important for general pediatricians to be aware of the common features and management.

  thumbsignMarfan_0.pngTinkle BT, Saal HM. Health supervision for children with Marfan syndrome. Pediatrics. 2013 Oct;132(4):e1059-72. PubMed PMID: 24081994

  • Incidence 1 in 3,000-5,000 people  
  • No strong variation among ethnicity
  • Autosomal dominant, 25% de novo mutation
  • Mutation in gene (FBN1)
    • Encoding the connective tissue protein, fibrillin-1
    • Causes systemic weakness of connective tissue

Physical Features and Clinical Manifestations

  • Joint hypermobility
  • Skin hyperelasticity
  • Striae
  • Long, thin extremities compared to trunk size (dolichostenomelia)
  • Long fingers (arachnodactyly, look for “thumb sign” and “wrist sign”)
  • Pectus excavatum
  • Scoliosis/kyphosis
  • Torticollis
  • Inguinal hernias
  • Tall stature
  • Flat feet (pes planus)
  • Acetabular protrusion
  • Long face
  • High palate arch (“steepled”)
  • Crowded teeth
  • Iridodonesis (rapid contraction and dilation of the iris)
  • Lens dislocation (ectopia lentis)
  • Myopia (elongation of the globe)
  •  Aortic dissection
  • Aortic root dilation leading to aortic regurgitation
  •  Mitral valve prolapse
  • Spontaneous pneumothorax (due to emphysematous change causing bullae formation)
  • Reduced pulmonary reserve
  •  Sleep apnea
  •  Dural Ectasia (stretching of dural sac in lumbosacral region)

 

Evaluation

Diagnosis of Marfan syndrome is based on the revised Ghent nosology.

  • Based on the degree of aortic root dissection (Z-score calculator available at http://www.marfan.org/dx/zscore), presence of ectopia lentis, and family history of MFS.
  • It can be challenging to apply diagnostic criteria to children < 20 years as some disease features are not yet present.
  • Additional categories of “nonspecific connective tissue disorder” and “potential MFS” can be used for those children without clear inclusion criteria.

Systemic involvement can be gauged using a point system with a score ≥7, which indicates major systemic involvement.

 

 Ghent_0.pngTinkle BT, Saal HM. Health supervision for children with Marfan syndrome. Pediatrics. 2013 Oct;132(4):e1059-72. PubMed PMID: 24081994

Signs and symptoms of Marfan syndrome vary widely in severity, timing of onset, and progression.

  • Annual exams are important for surveillance and intervention. These include the following:
    • Annual ophthalmologic examination for myopia and lens dislocation (especially as young children as they are at high risk for amblyopia)
    • Annual echocardiograms to monitor status of aortic root dilatation, aortic dissection, aortic tear or rupture, aortic regurgitation, mitral valve prolapse, tricuspid valve prolapse, and/or enlargement of the proximal pulmonary artery
    • Intermittent surveillance of the entire aorta with CT or MRA scans beginning in young adulthood
    •  Close monitoring for aneurysms and aortic arch dissection 

 

Mangement

Aortic disease is the most common cause of morbidity and mortality for patients with Marfan syndrome.

  • With evidence of progressive aortic root dilation, beta-blockers should be prescribed as they help decrease wall stress (ex. propranolol, atenolol, metoprolol), although efficacy in children has limited data.
  • In children with asthma, verapamil is recommended.

Other considerations include the following:

  • Restriction or limitation of vigorous physical exercise
  • Avoidance of sports with high risk of eye injury (ex. boxing, karate)
  • Elective surgical repair of the aorta and valves
  • Orthodontics for oromaxillofacial anomalies
  • Pulmonary function tests if significant respiratory complaints
  • Braces or surgery for scoliosis
  • Orthopedic intervention for complications of joint laxity
  • Screening of first degree relatives with echocardiogram
  • Genetic counseling
  • Support groups (ex. National Marfan Foundation)

 marfanfoundation_0_0.png

 

References

  1. Genetics, clinical features, and diagnosis of Marfan Syndrome.  UptoDate. http://www.uptodate.com/contents/genetics-clinical-features-and-diagnosi...
  2. Tinkle BT, Saal HM. Health supervision for children with Marfan syndrome. Pediatrics. 2013 Oct;132(4):e1059-72. PubMed PMID: 24081994
  3. The Marfan Foundation. 2015. Z-score Calculation. Retrieved from http://www.marfan.org/dx/zscore
  4. Genetics Home Reference. 2012 . Marfan Syndrome. Retreived from http://ghr.nlm.nih.gov/condition/marfan-syndrome
  5. Online Mendelian Inheritance in Man. 2015. Marfan Syndrome. Retrieved from http://www.omim.org/entry/154700
  6. National Human Genome Research Institute.2014 .learning about Marfan syndrome. Retrieved from https://www.genome.gov/19519224

 

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