Marilyn C. Higginbottom

The amniotic band disruption complex: Timing of amniotic rupture and variable spectra of consequent defects

Seventy-nine patients with the amniotic band disruption complex, including 54 infants with multiple system involvement and 25 with affected limbs alone, were evaluated. No two cases of the disorder were exactly alike. Defects varied from simple digital band constrictions to major craniofacial and visceral defects; fetal death may also occur. Amniotic rupture appeared to cause injury through three basic mechanisms: (1) interruption of normal morphogenesis; (2) crowing of fetal parts; and (3) disruption of previously differentiated structure. Comparison of 35 cases in which the timing of amniotic rupture could be estimated suggests that early amniotic rupture results in multiply affected infants who are frequently aborted or stillborn, whereas later rupture results primarily in limb involvement. Our findings indicate that both the spectrum of the developmental pathology and the nature of fetal outcome are determined by the timing of amniotic rupture. Appreciation of the mechanism which explains the disparate appearances of infants with the amniotic band disruption complex will allow more acurate diagnosis and appropriate counseling with respect to the sporadic nature of the disorder.

Compression-related defects from early amnion rupture: Evidence for mechanical teratogenesis

The features of 27 cases of limb/body wall deficiency (formerly termed cyllosomus and pleurosomus) were evaluated and the anomalies were interpreted as being band-related defects and/or compression-related defects. The latter included limb deficiency, body wall deficiency, neural tube defects, scoliosis, postural deformations, growth deficiency, and short umbilical cord. It is hypothesized that the single event of early amnion rupture can explain both the band-related defects and the compression-related defects. Experimental animal studies are in accord with this hypothesis; amnion puncture of rat fetuses during early gestation produces a comparable array of defects. The term amnion rupture sequence is suggested to describe the overall pattern of malformation that results from amnion rupture whether these defects are band related, compression related, or a combination of the two. There is considerable variation in the phenotype of amnion rupture sequence, with limb/body wall deficiency representing the more severe end of the spectrum. It is important to recognize and correctly diagnose amnion rupture sequence because it is usually a sporadic event.

Determining role of the optic vesicle in orbital and periocular development and placement.

Summary: Nine patients with aberrations in development and placement of the eyes and periocular structures who also had serious defects in central nervous system development were evaluated in order to better understand normal ocular development. Included were an incompletely developed twin stillborn infant who lacked both eyes and the nose, a stillborn infant with cyclopia bypognathia, 6 spontaneous abortuses with varying degrees of holoprosencephaly, and a 17-year-old male with a serious defect in central nervous system development whose right eye was positioned laterally above the right ear. In all cases, evidence indicates that orbital and periocular structures are determined by the underlying optic vesicle rather than independently derived as has been suggested by previous studies.Speculation: The intimate developmental relationship between the forebrain and structures of the upper face suggests that alterations of periocular and bony orbital structure and placement may well reflect defects in underlying brain development.