Two major patterns of nongenetic malformations are found at autopsy.

Patterns of malformations seen in autopsies may contribute to the understanding of their pathogenetic mechanisms. Two entities, acardiac twins (ATs) and amniotic band disruption complex (ABDC), have distinct patterns, indicating different mechanisms, namely vascular perfusion deficit and external disruption. With ATs and ABDC as model groups, this study was undertaken to see if other dysmorphic infants with the characteristic defects of these models formed distinct and numerically important groups. A total of 192 autopsies with nongenetic malformations was divided into groups including (1) those with defects found in the ATs but not in the ABDC, (2) those with defects found only in the ABDC, and (3) those with a mixture of exclusive defects from each model group. The cases followed the characteristic defects of ATs or ABDC in 20% (group 1) and 28% (group 2), respectively, forming 2 large and distinct groups; only 4% had mixed malformations (group 3). Group 1 had different characteristics from group 2 as a result of the frequent multiple malformations, often with congenital heart defects (CHDs), internal and inferior malformations. These cases were probably related to a vascular perfusion deficit. Group 2 had a majority of females and single, external, and superior defects, but it lacked CHDs and inferior malformations. These cases were likely due to external disruption. Two large and distinct groups of autopsies with nongenetic malformations were thus identified, and their mechanisms are proposed to be similar to those of the model groups.

Abdominal wall defects: autopsy findings of distinct groups suggest different pathogenetic mechanisms.

Central and lateral abdominal wall defects are probably distinct and likely arise from different pathogenetic mechanisms. An autopsy study was done using data from a total of 45 central and lateral abdominal wall defect cases to evaluate if they are indeed separate entities and to suggest possible mechanisms involved in their formation. Central defects were found to be statistically different from lateral defects; malformations that co-existed with central defects were mainly bilateral and internal and also involved "inferior" organs in relation to fetal-embryonal blood flow. Patients with lateral defects were more often female, and their coexistent defects were usually unilateral and external, with only 1 defect occurring in an "inferior" organ. These results indicate mechanisms of a vascular perfusion deficit for the majority of the central defects and of external disruption for the lateral defects.

Comparison of the amniotic band disruption complex with acardiac twins does not support its vascular origin.

The amniotic band disruption complex (ABDC) has been attributed to vascular disruption by some authors, not by others. Acardiac twins (ATs), however, have been generally accepted as a prime example of vascular disruption. In this study a comparison was made of these two entities to determine if they were similar or not, and thus we attempted to resolve the controversy of the mechanisms in the ABDC. A female tendency (2:1) was found in the ABDC in contrast to the "normal" sex distribution (0.88:1) in the ATs (p < 0.001). Most types of malformations (66%) were mutually exclusive, notably those of the cranium/brain, abdominal wall, and most internal organs; 83% were more significantly related to one or other of the entities. The ABDC malformations tended to occur unilaterally, but in the ATs they occurred bilaterally (p < 0.0001); the former tended to involve external organs and the latter internal organs (p < 0.0001). With so many differences, the two entities are unlikely due to the same mechanism: the ABDC is more likely to be due to external disruption.

The confused identity of Cantrell's pentad: ectopia cordis is related either to thoracoschisis or to a diaphragmatic hernia with an omphalocele.

To find out if Cantrell's pentad is a single entity, four cases of ectopia cordis were studied and compared with cases in the literature. Our cases had the heart outside the thorax and had two to four other features of the association. In one case the thoracic organs had apparently escaped through a diaphragmatic hernia into an omphalocele, and in the others via a thoracoschisis with an abdominal defect, either a supraumbilical hernia or a gastroschisis. According to these cases and those from the literature, it is proposed that there are two major mechanisms leading to ectopia cordis: (1) a reversed diaphragmatic hernia in the case of a large diaphragmatic defect and an omphalocele, and (2) through a sterno-costal defect, with gastroschisis or a supraumbililical abdominal defect. As omphaloceles and major diaphragmatic defects are probably pathogenetically distinct from thoraco- and thoracogastroschisis, it is important to distinguish these groups of anomalies, rather than be concerned as to their relationship with Cantrell's pentad.

Malformations of the cranium, vertebral column, and related central nervous system: morphologic heterogeneity may indicate biological diversity.

BACKGROUND: We conducted an autopsy study of neural tube defects (NTDs) to determine whether there is a relation between the localization of the lesion and the sex of the fetus or infant, and the presence of other malformations. METHODS: Included were 97 autopsies of infants/fetuses with anencephaly or spina bifida at any level and weighing more than 500 gm. The topographical divisions studied were: 1) isolated cranial lesions, 2) superior spina bifida with or without occipital lesion, and 3) isolated lower spina bifida. RESULTS: In group 1 (46 cases) there were lesions of the vertebral column, mainly cervical, and other anomalies of the "schisis" type. Group 2 (24 cases) showed more extensive involvement of the vertebral column and more cases with multiple anomalies (p = 0.001) of a varied spectrum, not only the schisis type; in group 3 (27 cases) the cases involved a few other malformations. In group 2 there was no sex preference (females 46%), but the other, more localized lesions (groups 1 and 3) were found predominantly in females (71%). CONCLUSIONS: Localized lesions, whether involving the cranium or lumbar spine, are formed by a mechanism that favors the female gender, whereas upper spina bifida, which is usually accompanied by cranial involvement, results from another mechanism (possibly vascular disruption) and is frequently accompanied by other malformations.

Malformations in acardiac twins are consistent with reversed blood flow: liver as a clue to their pathogenesis.

Because of the uncertainty concerning the origin of the malformations in the acardiac twin, its structure was studied to see if the malformations were random or with a pattern related to the twinning process. Included were 18 cases of dysmorphic twins in which an autopsy demonstrated a rudimentary or absent heart, and in which some polarity was evident. The organs and long bones with alterations were tabulated according to the embryonal-fetal circulation of blood from and to the placenta. Malformations were more often encountered in the superior limbs and organs; the number of altered organs decreased in a cranio-caudal direction. The liver was the exception being affected in 89% of the cases vs. an average of 54% for the other abdominal organs. As the liver lies first in the circulatory path from the placenta to the fetus, the pattern of the malformations was in accordance with the "twin reversed arterial perfusion sequence" (TRAP). The more frequent absence of distal bones (P = 0.0007) is compatible with reduced perfusion in each limb. The malformations found in the acardiac twins involved brain, esophagus and trachea, liver, other abdominal organs, diaphragm, vertebrae, limbs, anus, and omphalocele; vascular disruption may be the common pathogenesis for the acardiac twins as well as other dysmorphic infants with similar anomalies.

Congenital heart disease and its association with other congenital malformations found at autopsy.

The objective was to determine if a study of other malformations found autopsy in patients with congenital heart disease would contribute to an understanding of the mechanisms involved in the formation of these anomalies. In a large general hospital autopsies in children with congenital heart disease were selected, and the different cardiopathies were divided into 3 groups: those with isolated heart lesions, those with single gene mutants, as well as chromosome malformations, and those with idiopathic malformations not associated with a genetic syndrome. Because the cardiopathies most often associated with genetic syndromes were the septal defects in general (p = .001), it was presumed that these are influenced to a considerable extent by genetic factors. The association of left heart hypoplasia and coarctation of the aorta with multiple idiopathic malformations, particularly in the lower half of the body (p = .002), suggests that the latter may be due to vascular disruptions, because of the interruption of the flow of oxygenated blood in the embryo-fetus produced by these heart defects. Cranial defects were not associated with left heart obstruction, and are therefore unlikely to be produced by vascular disruption.

The implatantion site of a hydatidiform mole. One hundred years since the original description of Marchand

Se describe un caso de mola hidatidiforme in situ en una histerectomía. Hay invasión masiva de la decidua en el lugar de implantación por trofoblasto intermedio que manifiesta gigantismo nuclear, sugiriendo que el producto de un curetaje final del sitio de implantación sería más útil que el tejido de la mola hidrópica para otros estudios de ADN en relación al pronóstico