Ectopia lentis as the presenting and primary feature in Marfan syndrome

Am J Med Genet A. 2011 Nov;155A(11):2661-8. doi: 10.1002/ajmg.a.34245. Epub 2011 Sep 19.

Abstract

Marfan syndrome (MFS) is a multisystem connective tissue disorder with primary involvement of the ocular, cardiovascular, and skeletal systems. We report on eight patients, all presenting initially with bilateral ectopia lentis (EL) during early childhood. These individuals did not have systemic manifestations of MFS, and did not fulfill the revised Ghent diagnostic criteria. However, all patients had demonstratable, disease-causing missense mutations in the FBN1 gene. Based on molecular results, cardiovascular imaging was recommended and led to the identification of mild aortic root changes in seven of the eight patients. The remaining patient had mitral valve prolapse with a normal appearing thoracic aorta. The findings presented in this paper validate the necessity of FBN1 gene testing in all individuals presenting with isolated EL. As we observed, these individuals are at increased risk of cardiovascular complications. Furthermore, we also noted that the majority of our patient cohort's mutations occurred in the 5' portion of the FBN1 gene, and were found to affect highly conserved cysteine residues, which may indicate a possible genotype-phenotype correlation. We conclude that in patients with isolated features of EL, FBN1 mutation analysis is necessary to aid in providing prompt diagnosis, and to identify patients at risk for potentially life-threatening complications. Additionally, knowledge of the type and location of an FBN1 mutation may be useful in providing further clinical correlation regarding phenotypic progression and appropriate medical management.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / pathology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Ectopia Lentis / diagnosis
  • Ectopia Lentis / genetics
  • Ectopia Lentis / pathology*
  • Female
  • Fibrillin-1
  • Fibrillins
  • Genetic Association Studies
  • Genetic Testing
  • Genome, Human
  • Humans
  • Infant
  • Male
  • Marfan Syndrome / complications
  • Marfan Syndrome / diagnosis
  • Marfan Syndrome / genetics
  • Marfan Syndrome / pathology*
  • Microfilament Proteins / genetics*
  • Mutation, Missense
  • Pedigree
  • Retrospective Studies
  • Risk Factors
  • Young Adult

Substances

  • FBN1 protein, human
  • Fibrillin-1
  • Fibrillins
  • Microfilament Proteins