Histopathologic findings in ascending aortas from individuals with Loeys-Dietz Syndrome (LDS)

Joseph Maleszewski, Dylan V. Miller, Jie Lu, Harry C. Dietz, Marc K. Halushka

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder resulting from genetic mutations in the transforming growth factor β receptors 1 and 2 (TGFBR1 and TGFBR2). The syndrome is characterized phenotypically by hypertelorism, bifid uvula, and/or cleft palate, and arterial tortuosity with aneurysms and dissections. LDS has a much more rapid clinical course than Marfan syndrome (MFS) and thus those diagnosed with LDS are currently being recommended for prophylactic aortic root replacement at younger ages and with smaller aortic dimensions. Aortic root tissue obtained at surgery was compared between 15 patients carrying a diagnosis of LDS, 11 patients with MFS and 11 control aortas to evaluate the range of histopathologic changes in LDS. Standard hematoxylin and eosin and Movat pentachrome stains were performed. LDS samples had increased medial collagen and a subtle but diffuse form of elastic fiber fragmentation and extracellular matrix deposition, referred to as diffuse medial degeneration. LDS samples had significantly more diffuse medial degeneration compared with MFS and control samples (P<0.05), significantly less medial degeneration of the "cystic" variety compared with MFS (P<0.01) and significantly more collagen deposition than control samples (P<0.01). Additionally, an immunohistochemical stain for pSmad2, a marker of TGFβ activity, was significantly increased in LDS patients compared with controls (P<0.001). Overall, the histologic findings of LDS are best appreciated with special stains to evaluate fibrosis and elastic fiber fragmentation. The changes described, although not entirely specific for LDS, help differentiate this entity from other vascular diseases in the appropriate clinicopathologic setting.

Original languageEnglish (US)
Pages (from-to)194-201
Number of pages8
JournalAmerican Journal of Surgical Pathology
Volume33
Issue number2
DOIs
StatePublished - Feb 1 2009
Externally publishedYes

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Keywords

  • Ascending aorta
  • Loeys-Dietz Syndrome
  • Medial degeneration
  • Pathology
  • Transforming growth factor-b

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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