Limb body wall complex: I. Pathogenesis

Abstract

Twenty-five fetuses with limb body wall complex (LBW complex) were evaluated. The diagnosis was based on two out of three of the following: exencephaly/encephalocele with facial clefts; thoraco- and/or abdominoschisis; and limb defect. Ninety-five percent (24/25) of the fetuses had associated internal structural defects. In 72% (18/25) the internal defects have been recognized as being secondary to vascular disruption. Concordance was not found between the side and location of the body wall defect versus the limb, internal, and cranial defects. In 85% there was evidence for persistence of the extraembryonic coelom by examination of the placenta. In this same group (85%) there was persistence of the ectodermal-amnion margin, with the amnion being continuous with the skin of the body wall defect. In 40% (10/25) there were tags and amniotic adhesions at other sites. There was no difference in the types or incidence of internal defects between those with and those without amniotic bands. The abnormalities in this collection and experimental animal models support vascular disruption during 4-6 weeks' gestation as an etiology for LBW complex. There is disruption and loss of existing tissues, persistence of embryonic structures, and secondary malformations. Persistence of the extraembryonic coelom may lead to the typical amniotic tags, ring constrictions, and adhesions seen in some specimens.

Limb–body wall defect. Is there a defensible hypothesis and can it explain all the associated anomalies?

“…Van Allen et al [1987a] concluded that there was no correlation between either the cranio-caudal location or sidedness of the schisis and the internal or limb anomalies. Other authors have disagreed [e.g., Pagon et al, 1979;Russo and Vecchione, 1996;Craven et al, 1997;Luehr et al, 2002].…”

“…Finally, Hartwig et al [1989] proposed that the same ectodermal anomaly causes a deficiency of intermediate mesoderm and thus accounts for malformations such as renal agenesis. This seems contradicted by those cases where the abnormal organ is contralateral to the body wall defect [Van Allen et al, 1987a]. Furthermore the internal organs are known to derive from the inward migration of epiblasts at the primitive streak; the progenitors of the mesoderm.…”

“…Mastroiacovo et al [1992] found a rate of 0.03/10,000 for body wall defect with amelia, and 0.068/10,000 for body wall defect without amelia. A recent single center study that used LBWD as defined by Van Allen et al [1987a] obtained a significantly higher prevalence of 3.3/10,000 [Luehr et al, 2002]. Decreased maternal age has been suggested by Martinez-Frias et al [2000].…”

“…It is, however, the accompanying limb and cranial defects that have led to the most widely used rubric of Limb-Body Wall Defect or Complex [Van Allen et al, 1987a]. Pagon et al [1979] considered there to be three subtypes based upon the particular pattern of associated findings and the location and extent of the ventral wall defect (see the Discussion Section).…”

“…Since the seminal articles by Van Allen et al [1987a,b], most authors, sometimes not with strict adherence, have accepted those authors' definition of limb-body wall defect (LBWD) as requiring at least two out of three major manifestations of exencephaly/ encephalocele with facial clefts, thoraco-and/or abdominoschisis, and limb defects (any type). As had others before them, Van Allen et al [1987a] attempted to provide a single pathogenetic explanation, in their case vascular disruption, for the spectrum of anomalies observed. Much subsequent debate has revolved around the various pathogenetic hypotheses.…”