The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Article first published online: 2 SEP 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 152A, Issue 10, pages 2426–2436, October 2010
How to Cite
Sadler, T. W. and Rasmussen, S. A. (2010), Examining the evidence for vascular pathogenesis of selected birth defects. Am. J. Med. Genet., 152A: 2426–2436. doi: 10.1002/ajmg.a.33636
How to Cite this Article: Sadler TW, Rasmussen SA. 2010. Examining the evidence for vascular pathogenesis of selected birth defects. Am J Med Genet Part A 152:2426–2436.
- Issue published online: 20 SEP 2010
- Article first published online: 2 SEP 2010
- Manuscript Accepted: 7 JUL 2010
- Manuscript Received: 1 APR 2010
- vascular mechanism;
- limb defects;
- oculoauriculovertebral spectrum;
- intestinal atresia
Vascular mechanisms have been proposed to be involved in the pathogenesis of a number of defects, including transverse-limb defects, intestinal atresias, gastroschisis, hydranencephaly, porencephaly, oromandibular-limb hypogenesis sequence, and oculoauriculovertebral spectrum (OAVS). Here, we examine the available clinical, epidemiologic, and experimental evidence for four defects (transverse-limb defects, intestinal atresias, gastroschisis, and OAVS) for which vascular pathogenesis has been hypothesized. Based on our review, transverse-limb defects appear to sometimes be due to vascular events related to placental vascular abnormalities, hypoperfusion, abnormal development of blood vessels, intrauterine compression, hemoglobinopathies, or exposure to vasoactive agents, although epidemiological studies have not consistently demonstrated the latter association. However, transverse-limb defects can also be due to abnormal developmental events, such as aberrant molecular signaling in the apical ectodermal ridge. Some intestinal atresias may have a vascular origin, with the hypothesis supported by experiments in canines. However, evidence is accumulating that a more common mechanism might be related to improper molecular signaling related to gut specification early in development. In contrast, evidence to support vascular pathogenesis for gastroschisis and OAVS is less compelling. Instead, these defects probably arise from interference with basic developmental events [e.g., body wall closure (gastroschisis) and neural crest cell development (OAVS)]. These conclusions are important for counseling parents of children with these defects and for guiding the design of future epidemiological studies and experiments to further characterize the causes of these defects. © 2010 Wiley-Liss, Inc.