Caudal dysgenesis and sirenomelia-single centre experience suggests common pathogenic basis

Am J Med Genet A. 2010 Oct;152A(10):2578-87. doi: 10.1002/ajmg.a.33599.

Abstract

Abnormally formed lower limbs with varying degrees of fusion are the major feature of sirenomelia whereas maldeveloped lower limbs without fusion are found in association with caudal dysgenesis (CD). The relationship between these two entities has been a topic of debate for many years. The presence of a single umbilical artery originating from the abdominal aorta was considered a major feature distinguishing sirenomelia from CD. Based on this finding, the vascular steal theory was put forward as the causative mechanism of sirenomelia. CD and sirenomelia were considered to be two entirely different entities with distinct pathogenic mechanisms. However, it is now clear that a single umbilical artery can be found in some patients of CD and normal umbilical arteries in some patients of sirenomelia. The hypothesis of primary deficiency of caudal mesoderm caused by early developmental disruption suggests that sirenomelia and CD are two ends of a spectrum of maldevelopment of caudal mesoderm. In this paper we report on the clinical and pathological features of 16 patients of CD and 9 patients of sirenomelia from our institution and review the literature. This series of cases is notable for the significant association with neural tube defects, refining the renal and urogenital pathology associated with these conditions, and supporting the concept of a continuum of the disease spectrum.

MeSH terms

  • Abnormalities, Multiple / etiology
  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / pathology*
  • Autopsy
  • Blood Vessels / pathology
  • Ectromelia / etiology
  • Ectromelia / genetics
  • Ectromelia / pathology*
  • Female
  • Humans
  • Pregnancy
  • Ultrasonography, Prenatal
  • Umbilical Arteries / pathology
  • Vascular Diseases / complications
  • Vascular Diseases / genetics