摘要:

AbstractNew molecular techniques concerned with the isolation and identification of DNA fragments can be used for carrier detection and early prenatal diagnosis either by direct detection of the mutant DNA sequence or by indirect linkage studies employing RFLPs as DNA markers. Gene specific DNA probes are available already for a number of genetic disorders, such as the hemoglobinopathies, hemophilia A and B, α1‐antitrypsin deficiency, phenylketonuria, and chronic granulomatous disease. Coinheritance of DNA‐polymorphisms can be traced, eg, for Norrie disease, myotonic dystrophy, Duchenne and Becker muscular dystrophies, and Huntington chorea. Several genes have been localized successfully to specific chromosome regions. By “walking” or “jumping” along the chromosome, it is hoped finally to reach further gene loci of interest, to analyze the molecular pathology of single gene disorders, and to find new ways for thei

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280504

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractNew insights into gene structure and expression and the observation that homeobox‐containing genes, thet‐complex, and oncogenes are expressed also in humans contribute to the understanding of normal and pathobiological mechanisms of embryonal and fetal developm

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280505

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThe human midline is particularly vulnerable to dysmorphogenesis. This property can be derived theoretically from models of developmental fields that rely on positional information for the control of the process of determination. The topological properties of the midline as an early plane of symmetry imply positional informational weaknesses that should decrease developmental stability in this area for 2 reasons: 1) the unique location on a cusp between 2 mirror image fields is a “null” position for differentiation, and 2) this location between 2 equal positional values eliminates a lateral gradient that aids in regaining information after disruptions. Under this model, midline malformations would be expected to be primarily determinative defects, with an especial, proclivity for patterning and tissue abnormalities. Evidence is presented in support of this hypothesis, which makes midline properties consequences of developmental field properties, even though, technically speaking, the midline would not itself be a fi

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280506

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractIt has been suggested that complexes of multiple congenital malformations, involving limbs and viscera, may be caused by embryonic neural crest injury. Structures supplied by the sensory and autonomic nerves derived from the injured zone of crest would suffer defective development through presumed impairment of neurotrophic influence. Our study aimed to examine this concept by a retrospective analysis of autopsy findings in 27 babies who died of multiple congenital malformations associated with longitudinal limb defects. Sclerotome maps of the segmental sensory innervation of the skeleton were used to analyse the limb defects in terms of their nerve supply. From a review of the literature, the approximate segmental contribution of neural crest to the autonomic innervation of internal organs was ascertained, and thus “viscerotome” diagrams were constructed. Application of sclerotomes and viscerotomes to the data derived from the autopsy reports showed a neuroanatomic correlation in 89% of cases. Interpretation of multiple malformation syndromes is proposed on the basis of neurotomes, or embryonic developmental fields with common regional innervat

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280507

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThe DiGeorge anomaly (DGA) represents a polytopic developmental field defect that can be caused by a number of different chromosomal, mendelian, toxic, or metabolic factors operating in early embryonic life. If the affected field is thought to be focused on either the fourth branchial arch or the third branchial pouch, with variable cephalad or caudad extension, 38 different combinations of malformations can include DiGeorge anomalies, 24 complete and 14 partial DGA, with the constraints that the field defect must be contiguous (involvement of more than one branchial arch or pouch requires involvement of all intervening arches or pouches) and complete (all derivatives of an affected branchial arch or pouch are deficient). The types and relative frequencies of abnormalities of structures other than the thymus and parathyroid glands in these possible “subsets” of DGA are discussed, and the need for more data on their occurrence in patients diagnosed as having DGA is emphasi

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280508

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractAn analysis of 52,198 pregnancies was undertaken to determine if male and female fetuses had differing environmental effects on their mothers. Early gestational blood pressure and weight gain were significantly higher in preeclamptic women with male than with female fetuses. Preeclamptic women had lower third trimester hemoglobin values and less frequent proteinuria with male than with female fetuses. Excessive syncytial knots, a characteristic placental consequence of low uteroplacental blood flow, were seen less frequently with male than with female fetuses. These findings are hypothesized to be due to a greater maternal blood plasma volume expansion with male than with female fetuses in preeclamptic pregnancies.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280509

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractOld and new data on the size of the human parietal bone are presented. Attention is drawn to zonal changes in the configuration of the bones, particularly in fetuses and newborn babies, that almost certainly indicate phasic variations in the growth rate of the baby, and it is suggested that the estimation of the size of the bone where these abnormal zones occur may be a guide as to the intrauterine age of the child when the alteration in growth occurred. Parietal bone size could also be a help in describing local and general skeletal dysplasias.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280510

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractPosterior cervical hygroma, once considered diagnostic of fetal Ullrich‐Turner syndrome, is now recognized as being a nonspecific malformation found in a number of unrelated conditions. We have studied 61 fetuses of 10–23 developmental weeks from therapeutic and spontaneous abortions who had posterior cervical hygroma. We found that the group was indeed markedly heterogeneous, for both sexes were represented, and a variety of genetic and nongenetic disorders were present, such as trisomy 18, 21, and probably also 13; lethal multiple pterygium syndrome; Noonan syndrome; isolated congenital heart defect, isolated pterygium colli; and monosomy X (45,X). Unlike any of the other conditions, 45,X fetuses had a constant association of 3 defects—posterior cervical cystic hygroma, generalized subcutaneous oedema, and prcductal aortic coarctation. Therefore, we suggest that this triad is diagnostic of lethal Ullrich‐Turner syndrome in the fetal period and that it may be used reliably to diagnose the syndrome in fetuses when chromosome analysis is impossible. Further, since preductal coarcta‐tion of the aorta is found in only a small proportion of liveborn girls with Ullrich‐Turner syndrome, but occurred in all aborted fetuses in our study, we suggest that this abnormality is related to the lethality of the 45,X chromosome constitution during fetal

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280511

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractWestern medicine is being sensitized to the enormous extent of prenatal death in humans at a time when such deaths, occurring after the first missed period, involve to an ever increasing degree wanted pregnancies conceived by women with rising mean maternal age, decreasing mean fertility, and ever greater desire and intention to assure a good pregnancy outcome. Available data suggest that about two‐thirds of human ova, embryos, and fetuses fail to reach birth or the end of the first year of life, with infant mortality of 1.06%, stillbirth rate of 8/1,000, abortion rate of about 15%, and death rate around the time of implantation estimated at 34%. Based on limited data on sperm, ova aspirated from Graafian follicles in infertile women, direct observation of a few implanting ova, the low rate of human fecundity, and the high failure rate of in vitro fertilization, it seems reasonable to suppose that about 30% of human ova perish at the time of fertilization and before implantation. Most of this prenatal death is attributable to chromosome abnormalities (aneuploidy and polyploidy), estimated to be present at the beginning of development in about half of all human ova or embryos.Parent's anguish about prenatal death and their desire to understand its causes and to prevent recurrence is putting the medical profession under severe pressure to provide diagnostic and counseling services and make available prenatal diagnosis and preventive approaches; this comes at a low point in the ability of Western medicine to respond adequately, especially in the fields of embryology and developmental genetics, clinical teratology, anatomical pathology, and genetic pathology. Unless drastica ameliorative measures are taken, the situation is likely to get much worse, since health insurance pays for only a minute fraction of costs involved and the number of pediatric pathologists devoting major effort to this work in North America has dwindled to a small number without great hope for replacement from younger ranks, primarily as a result of the lack of incentive by the tertiary centers to make fetal genetic pathology (“morphology”) an attractive field to work in.Here we report an effort by a secondary care center to provide such a service—presently more on demand than as systematic effort to reach all at need—in a huge, underpopulated state with birthrate of less than 13,000 and lacking any psecially trained pathologist with a strong interest int he field. The reson this is less quixotic than might appear at first is because the Montana Fetal Genetic Pathology Program is being conducted in collaboration with the Pediatric Pathology Program of the University of Wisconsin directed by Dr. Enid F. GIlbert, a world leader in the field, to guarantee the highest standards of performance and interpretation of findings.Preliminary data on the first 400 cases studied over the past 5 years suggest that cause of death is identifiable in over three‐fourths of all cases; in 56% a fetal cause and in 21% a suspected placental or uterine cause is postulated. Cerain advances of this appraoch—a combined attempt to provide service and to advance the field—are suggested, provided that practical requirements for such a program are met and adquately funded from an

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280512

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractWe have reviewed spontaneously aborted fetuses of 9 to 20 developmental weeks. All fetuses with either external or internal developmental defects and those with maternal history of repeated spontaneous abortion were studied cytogenetically. Among 723 fetuses the cytogenetically proven prevalence of chromosome abnormalities was 5.8%. Inclusion of suspected chromsome abnormality based on morphologic findings resulted in an overall prevalence of only 7.1%. This prevalence and restricted spectrum of chromosome abnormalities, which included monosomy X, triploidy, gonosomal aneu‐ploidy, trisomies 13, 18, and 21, resembled the prevalence and spectrum found among perinatal deaths and differed both in prevalence and type from those chromosome abnormalities found in spontaneous abortions occurring during the embryonic period.Monosomy X was the most common chromosome abnormality among previable fetuses. Both monosomy X and triploidy were more frequently detected in the early fetal period than in perinatal deaths. The combined prevalence of autosomal trisomies was equal to that which has been reported in perinatal deaths. Chromsomal structural abnormalities, seen in perinatal deaths, were not found in our stud

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280513

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY