Pentalogy of Cantrell and ectopia cordis,a familial developmental field complex

The association of sternal fusion defects with various cardiac, diaphragmatic, and anterior body wall defects represents a developmental field complex that includes the Pentalogy of Cantrell and ectopia cordis. No familial cases have been reported previously. We present 3 consecutively born brothers with extensive diaphragmatic defects, 2 who had the Pentalogy of Cantrell. One of the 2 also had ectopia cordis.     

Pentalogy of Cantrell and associated midline anomalies: a possible ventral midline developmental field.

Five cases of the Pentalogy of Cantrell (PC), ascertained through the Baltimore-Washington population-based study of infants with congenital cardiovascular malformations, represent a regional prevalence of 5.5/1 million liveborn infants for this disorder. Three of these patients had cleft lip with or without palate. Review of the reported literature of the Pentalogy of Cantrell and various combinations of the anomalies within the spectrum of this pentad suggests that the PC defines a specific midline ventral developmental field. Cleft lip with or without cleft palate and encephalocele tend to specifically associate with ventral midline anomalies within the spectrum of PC. These associations might either illustrate the previously observed tendency of specific occurrence of certain combinations of midline defects or represent defined subunits of the midline developmental field.     

Pentalogy of Cantrell and associated midline anomalies: A possible ventral midline developmental field

Five cases of the Pentalogy of Cantrell (PC), ascertained through the Baltimore–Washington population-based study of infants with congenital cardiovascular malformations, represent a regional prevalence of 5.5/1 million liveborn infants for this disorder. Three of these patients had cleft lip with or without palate. Review of the reported literature of the Pentalogy of Cantrell and various combinations of the anomalies within the spectrum of this pentad suggests that the PC defines a specific midline ventral developmental field. Cleft lip with or without cleft palate and encephalocele tend to specifically associate with ventral midline anomalies within the spectrum of PC. These associations might either illustrate the previously observed tendency of specific occurrence of certain combinations of midline defects or represent defined subunits of the midline developmental field.     

Two rare cases of the Pentalogy of Cantrell or its variants

The Pentalogy of Cantrell (PC) is a rare association of defects involving the lower sternum, abdominal wall, diaphragm, pericardium and heart. We report two rare cases of the PC (variant form), showing fatal progression. Case 1 only survived two hours because of severe cardio-respiratory failure. Physical examination showed midline abdominal and thoracic defects, ectopic heart, pericardial defect, diaphragmatic defect, bilateral undescended testis, scoliosis, and adherence between left upper limb and trunk. In addition, the autopsy revealed diaphragmatic agenesia, intraabdominal testis, bilateral lung hypoplasia and lymphocytic meningitis. Case 2 only survived 15 minutes. In addition to the physical findings, including lower sternal defect, ectopic heart, epigastric omphalocele and scoliosis, the autopsy showed left diaphragmatic agenesia, pericardial agenesia, bilateral lung hypoplasia, deformed rib cage, anterior thoracic myeloschisis, adreno-hepatic fusion, left renal agenesia, meckel diverticulum and multiple accessory spleens. When comparing with other cases of PC, the concurrence of bilateral intraabdominal testis and lymphocytic meningitis in case 1, and adreno-hepatic fusion, anterior myeloschisis, meckel diverticulum, multiple accessory spleens, and renal agenesia in case 2 have not been described previously.     

Trisomy 18 associated with ectopia cordis and occipital meningocele

A premature infant presented with ectopia cordis, occipital meningocele, and manifestations of trisomy 18; cytogenetic analysis confirmed a 47,XX,+18 chromosome constitution. While most cases of ectopia cordis appear as isolated, sporadic defects, careful evaluation is warranted to detect evidence of an associated chromosome abnormality.     

Transmission of electric and magnetic foetal cardiac signals in a case of ectopia cordis: the dominant role of the vernix. caseosa

Foetal electrocardiograms (fECGs) and foetal magnetocardiograms (fMCGs) were recorded in the 26th, 29th and 31st weeks of gestation from a foetus with ectopia cordis-a rare condition in which the heart lies outside the chest wall. This provided an opportunity to study foetal cardiograms uninfluenced by the insulating effects of the foetal skin and vernix caseosa. The fECG of the ectopia cordis foetus was striking. Unlike recordings from age-matched normal foetuses, recordings from this subject had very high signal-to-noise ratio and showed no anomalous signal transmission properties. In contrast, fMCGs recorded from the ectopia cordis foetus and normal foetuses were largely similar. Both showed high signal-to-noise ratio and signal transmission properties consistent with volume conduction. The findings corroborate the hypothesis that high foetal skin resistance due primarily to the vernix caseosa is responsible for the low amplitude and anomalous transmission properties of the normal fECG, and demonstrate that the fMCG is relatively insensitive to conductivity inhomogeneities.     

Holoprosencephaly: a developmental field defect

Holoprosencephaly refers to a spectrum of craniofacial malformations including cyclopia, ethmocephaly, cebocephaly, and premaxillary agenesis. Etiologic heterogeneity is well documented. Chromosomal, genetic, and teratogenic factors have been implicated. Recognition of holoprosencephaly as a developmental field defect stresses the importance of close scrutiny of relatives for mild forms such as single median incisor, hypotelorism, bifid uvula, or pituitary deficiency.     

Primary midline developmental field. I. Clinical and epidemiological characteristics

Opitz [BD: OAS XXIX(1): 3-37, 1993] has postulated that during early blastogenesis the entire embryo represents a single morphogenetic unit, the primary field. During this period, beginning gastrulation, the most important events are the formation of the midline and the mesoderm. Consequently, one could expect that dysmorphogenetic reactions of the primary field are likely to disturb more than one of the essential events of blastogenesis, such as fusion, lateralization, decussation, segmentation, morphogenetic movements, asymmetry formation, etc. I have used the 20,891 liveborn malformed infants identified by the Spanish Collaborative Study of Congenital Malformations (ECEMC) to analyze the concept of the primary field defect (DFD). The malformed children were separated into 4,679 children with only midline defects, 1,592 children with midline plus other non-midline anomalies, and 14,620 babies without midline defects. Sex, twinning, neonatal death, parental consanguinity, and other malformed first degree relatives in the family were analyzed in each group. Different defects were selected as indicators of specific morphogenetic events of blastogenesis. Cardiac and neural tube defect were selected as indicators of fusion anomalies; agenesis/hypoplasia of the corpus callosum were included as example of decussation defect; cyclopia as representation of the alteration of lateralization; vertebral defects as indicators of anomalies of segmentation; intestinal malrotation and omphalocele as representatives of the alteration of the morphogenetic movement; and, finally, infants with asplenia, polysplenia, dextrocardias, transposition of great vessels, visceral transposition, and situs inversus totalis were grouped to allow an analysis of alteration of the normal body asymmetry. The results of this analysis demonstrate, from an epidemiological standpoint, that the infants with midline anomalies have alteration of the normal body asymmetry more frequently than infants without midline defects. Children with midline anomalies have more severe malformations with high lethality, associated with twinning, without sex differences in occurrence, and with low recurrence risk, than do infants without midline defects, as was suggested by Opitz [BD: OAS XXIX(1): 3–37, 1993]. © 1995 Wiley-Liss, Inc.     

VACTERL as primary, polytopic developmental field defects

Previously we proposed that the VACTERL association represents a dysmorphogenetic response of the primary developmental field, i.e., polytopic developmental field defects (DFD). As such, it should conform to the essential attributes of a DFD, namely, heterogeneity, homology, and phylogeneity. To study its heterogeneity, we analyzed the data of the Spanish Collaborative Study of Congenital Malformations (ECEMC). Our results confirm the observations indicating that the different patterns of defects that constitute this entity are not only clinically variable but also causally heterogeneous. This causal heterogeneity, which is of crucial importance in defining developmental fields, gives additional credence to the hypothesis that VACTERL constitutes a primary polytopic DFD.     

家族性染色体复杂重排的分子细胞遗传学研究

目的 用分子细胞遗传学技术确诊染色体复杂重排，并探讨其临床效应。方法对1例涉及5号、16号和20号染色体复杂重排核型的男性携带者，应用多色荧光原位杂交和显微切割技术进一步分析确定其核型，并进行家系调查。结果该病例为涉及5号、20号及16号染色体复杂易位，并伴有20号染色体的一个带插入到5号染色体。家系调查发现该病例的母亲及妹妹均有相同的染色体异常。结论多色荧光原位杂交结合显微切割技术能够确诊染色体复杂结构重排。染色体复杂重排仍可在家庭中稳定传递，携带者具有出生正常后代的可能。     

Limb-pelvis hypoplasia/aplasia: A discrete entity in the fibuloulnar developmental field complex

The limb-pelvis hypoplasia/aplasia (LPHA) syndrome is a rare condition of skeletal malformations affecting the ulnae, pelvic bones, fibulae and femora, sometimes associated with extraskeletal defects. Most reported patients are from the Middle East, and autosomal recessive inheritance was clearly demonstrated on the basis of multiple occurrences of affected sibs born to consanguineous matings. Here we report on a baby girl presenting with the phenotypic characterics of LPHA. This is second observation of LPHA from Italy, and the fourth outside the Middle East. A paternal first cousin once removed had unilateral fibular hypoplasia and absence of the the 4th and 5th digital rays. The possible link between these cases is discussed in the light of the developmental field theory. Am. J. Med. Genet. 68:190–194, 1997 © 1997 Wiley-Liss, Inc.     

Successful Vaginal Delivery of a Pregnant Woman with Cantrell's Pentalogy

Cantrell''s Pentalogy is a rare condition that consists of defects involving the abdominal wall, lower sternum, anterior diaphragm, pericardium, and heart. In the literature to date, pregnant women with Cantrell''s Pentalogy have not been discussed. We performed successful vaginal delivery of a 23-yr-old nulliparous, primigravid woman who had been diagnosed with this condition. Diagnosis was based on cardiac catheterization, angiography, and echocardiogram, and abdominopelvic CT. Vaginal delivery may be an option for women with Cantrell''s Pentalogy and may be attempted with caution.     

Differentiation and developmental origin of cerebellar granule neuron ectopia in protein O-mannose UDP-N-acetylglucosaminyl transferase 1 knockout mice

The cerebellar cortex of protein O-mannose UDP-N-acetylglucosaminyl transferase 1 (POMGnT1) knockout mice contains discrete clusters of granule neurons that fail to migrate from the external germinal layer (EGL) to the internal granule cell layer (IGL). To test the hypothesis that the breaches in the pial basement membrane and glia limitans contribute to the formation of such heterotopias, POMGnT1 deficient mice were used to examine the mechanisms underlying these migration defects. The basement membrane, glia limitans, and granule neuron development were assessed with protein markers and immunofluorescent microscopy. Further, the integrity of the pial basement membrane, and granule neuron differentiation state were assessed by electron microscopy. Localized breaches in pial basement membrane and disruptions in the glia limitans were strongly associated with ectopia of EGL cells. In such ectopias, Bergmann glia fibers were retracted and disorganized with very few protruded into the ectopic area. Thus, migration failure was correlated with a compromised Bergmann glia scaffold. Nevertheless, the ectopic EGL cells showed characteristics of differentiated granule neurons and formed synapses with mossy fibers. Altogether, these results suggest that pial basement membrane breaches and glia limitans disruptions are the underlying causes of cerebellar granule neuron ectopia in POMGnT1 knockout mice. Moreover, migration into the IGL is not required for granule cell acquisition of certain differentiated characteristics.