Severe aortopathy due to fibulin-4 deficiency: molecular insights, surgical strategy, and a review of the literature

Eur J Pediatr. 2014 May;173(5):671-5. doi: 10.1007/s00431-013-2217-y. Epub 2013 Nov 26.

Abstract

Mutations in the EFEMP2 (alias FBLN4) gene, which encodes the extracellular matrix protein fibulin-4, lead to severe aortopathy with aneurysm formation and vascular tortuosity. The disease phenotype, termed autosomal recessive cutis laxa type 1B (ARCL 1B), is rare among heritable connective tissue diseases but becomes more likely when noting family consanguinity and loose, inelastic skin in the patient. Our patient presented with an intercurrent illness exacerbating upper airway obstruction due to compression from a large aortic aneurysm. Genetic testing eventually revealed the causative mutation. She was initially treated with an angiotensin II receptor blocker and beta-blocker and eventually underwent total thoracic aortic replacement via a two-stage elephant trunk-type procedure. She recovered well and is currently asymptomatic but will require lifetime follow-up due to residual vascular tortuosity and aneurysm risk.

Conclusion: Better understanding of the importance of transforming growth factor beta signaling in the pathophysiology of aortopathies such as ARCL 1B has led to targeted medical therapies. Specific surgical techniques can lead to optimal outcomes in these patients.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Aortic Aneurysm / diagnosis*
  • Aortic Aneurysm / surgery*
  • Blood Vessel Prosthesis Implantation
  • Bronchoscopy
  • Cutis Laxa / diagnosis*
  • Cutis Laxa / surgery*
  • Diagnosis, Differential
  • Diagnostic Imaging
  • Extracellular Matrix Proteins / deficiency*
  • Female
  • Humans
  • Infant
  • Tracheostomy

Substances

  • EFEMP2 protein, human
  • Extracellular Matrix Proteins

Supplementary concepts

  • Cutis Laxa, Autosomal Recessive, Type I