The syndrome of proximal femur, fibula, and midline metatarsal long bone deficiencies

David R. Hootnick (Corresponding Author), Neil Vargesson

Research output: Contribution to journalArticle

2 Citations (Scopus)
2 Downloads (Pure)

Abstract

Human lower extremity congenital long bone deficiencies cluster primarily at three distinct skeletal loci. Proximal femoral and fibular reductions are known phenomena. In contrast, midline metatarsal deficiencies have been misrepresented as lateral. The popular term, ‘fibular hemimelia’, is inaccurate and its use is discouraged.
All three loci correspond to discrete sites of evolving angiogenesis during transition from a single embryonic axial limb artery to the familiar and complex adult arterial pattern. Initiation of bone formation of cartilaginous primordia of the long bones at all three sites occurs in proximity to, and depends upon, successful invasion by mature nutrient vessels, formed during sixth and seventh weeks of embryonic development. The adult arterial pattern is fully established by eighth embryonic week.
Arterial transitions occur later in development, around the time of cessation of the molecular processes of patterning/specification of the embryonic limb. Evidence of flawed embryonic arterial transitions, involving missing, reduced and/or retained primitive vessels in association with congenital skeletal reductions have been demonstrated at all three loci.
Current molecular models of limb development do not explain the distribution of this triad of congenital skeletal reductions. Dysmorphologies are most accurately described as postspecification errors of limb development. Recognition of this distinctive model of limb maldevelopment demands further investigation to create a more exact taxonomy, one consistent with both clinical and molecular criteria. The established terminologies originated by Frantz and O’Rahilly should be abandoned. Designation of this clinical triad as a syndrome of proximal femur, fibula and midline metatarsal dystrophisms initiates that endeavor.
Original languageEnglish
Pages (from-to)1188-1193
Number of pages6
JournalBirth Defects Research
Volume110
Issue number15
Early online date27 Aug 2018
DOIs
Publication statusPublished - 1 Sep 2018

Keywords

  • arterial transition
  • developmental growth failure
  • dystrophism
  • long bone deficiency
  • proximal femoral focal deficiency
  • fibular deficiency
  • midline metatarsal deficiency
  • post-specification errors

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