摘要:

AbstractTwenty‐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 de‐fects. 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 som

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280302

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

年代:1987

数据来源: WILEY

摘要:

AbstractLimb defects from 25 fetuses with limb‐body wall (LBW) complex were evaluated to determine the mechanism of limb damage. The limb defects could be divided into 3 pathogenetic groups: (1) secondary to disruption of embryonic vessels and surrounding tissue (84%), (2) secondary to amniotic bands or adhesions (16%), and (3) deformation versus hemorrhage (44% with club feet), with some fetuses having more than one pathogenetic mechanism causing limb defects. The hypothesis that the majority of limb defects resulted from disruption of embryonic vessels was supported by the following findings: 96% of the LBW complex fetuses had limb defects; the lower limbs were at greater risk of damage than the upper limbs (28% rt arm, 52% 1t arm, 60% rt leg, 72% lt leg); there was a distal to proximal progression of limb damage in 92% of the fetuses; statistical analysis of comparing the location of the most severe limb defect and the body wall defect did not find concordance between the side (p = l.0) and the region (p = 0.18) of the body wall defect; and limb defects found in the human specimens were similar to those produced in experimental animals following disruption of embryonic vessels at a corresponding gestation. In the specimens with amniotic band related limb defects (16%), the most likely pathogenesis is mechanical rupture through the amnion in the presence of a persistent extraembryonic coelom or from adhesion of the amnion to necrotic embryonic tissue after the initial disruptive event. Club feet were present in 44% and may be due either to disruption of embryonic vessels or to deformation. Further studies are needed to resolve this questio

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280303

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

年代:1987

数据来源: WILEY

摘要:

AbstractTwo white females, age 2 1/2 and 33 years, respectively, were investigated because of severe mental retardation associated with neurologic abnormalities, coarse face, and soft tissue syndactyly involving upper and lower limbs. Each had cytogenetic findings of a mosaic variant of Ullrich‐Turner syndrome with X ring chromosome in peripheral lymphocyte and skin fibroblasts. Early X replication occurred in one‐third of the X ring chromosomes; there was no evidence for X‐autosome translocation involving either X and an autosomal duplication; results of studies for fragility of the X chromosomes were unremarkable. In situ hybridization with an X centromere probe was positive for the ring. To our knowledge, the unusual constellation of cytogenetic, physical, and mental findings seen in these 2 individuals has not been reported previ

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280304

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

年代:1987

数据来源: WILEY

摘要:

AbstractA patient with partial duplication 2q and partial deficiency 11q is reported. The propositus was delivered at 30 weeks gestation, with a birth weight of 1,390 g. He had severe hyaline membrane disease, intraventricular hemorrhage, bronchopulmonary dysplasia, hypotonia, psychomotor retardation, hearing loss, and other anomalies including a short bitemporal diameter, prominent occiput, low‐set ears, exophthalmos, short nose with depressed nasal root, downturned mouth corners, narrow high‐arched palate, micrognathia, a deep longitudinal groove over the sacrococcygeal region, clinodactyly, and abnormal dermatoglyphics. Chromosome analysis showed the following karyotype: 46,XY,der 11,t(2:11)(q32.2;q25)

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280305

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

年代:1987

数据来源: WILEY

摘要:

AbstractCraniofrontonasal dysplasia, a distinct malformation syndrome, is characterized by varying degrees of frontonasal dysplasia, craniosynostosis, and variable extracranial abnormalities—in particular, brittle nails with prominent longitudinal grooves or Splitting. There is marked female preponderance and variable expressivity not only between males and females but also between females. However, mode of inheritance is still unclear. We describe a large Arab kindred with 16 individuals (9 males, 7 females) in 4 generations having an apparently new autosomal dominant syndrome with features of Craniofrontonasal dysplasia but with normal or slightly broad nasal tip and without evidence of craniosynostosis or nail abnormalities. These cases were segregating in 5 sibships and include male to male transmission with full expression in males and females. Chromosomes of the proposita and her father were normal. Aarskog syndrome has been also considered in the differential diagnosis and was exclude

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280306

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

年代:1987

数据来源: WILEY

摘要:

AbstractThe effect of colchicine at concentrations of 0.25 × 10−6M, 1.0 × 10−6M, and 2.0 × 10−6M on the degree of satellite association (SA) was estimated in phytohemagglutinin‐stimulated lymphocytes of individuals in the following groups: cystic fibrosis (CF) children, obligatory CF heterozygotes, control children, and control adults. In all four groups increasing colchicine concentration caused a higher degree of SA. The degree of SA differed between the two control age groups (children vs adults) only at the lowest concentration. CF patients had a significantly higher degree of SA than CF heterozy gotes and than control individuals at all colchicine concentrations; CF heterozygotes had a significantly higher degree of SA than control adults at the low and intermediate concentrations. There was a strong interaction between genotype and colchicine concentration: the differences between the CF patients and the control individuals were most distinct at the intermediate concentratio n and between the carriers and the control individuals at the low colchicine concentration. Colchicine had no effect on the activity of the nucleolar Organizer regions (NORs), as measured by the frequency of the silver‐stained NORs (AgNORs), while the frequency of AgNORs in CF patients was significantly lower as compared to control individuals. Yet, the increase in the degree of SA caused by the CF mutant allele involved specifically the satellited chromosomes carrying

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280307

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

年代:1987

数据来源: WILEY

摘要:

AbstractOur recent studies of the teratogenic mechanisms of phenytoin (DPH) and glucocorticoid in mice have indicated that DPH utilizes the anti‐inflammatory pathway of glucocorticoids in producing congenital defects, such as cleft palate. This pathway is influenced by H‐2 and H‐3 histocompatibility‐linked genes in the mouse, such that congenic strains have H‐2 or H‐3 alleles that confer susceptibility to DPH‐induced‐induced congenital defects, and susceptible H‐2 congenic strains have high glucocorticoid receptor levels. However, other H‐2 or H‐3 alleles confer resistance to these defects in their otherwise genetically identical congenic partner strains, and “resistant” H‐2 alleles are associated with low levels of these receptors.To determine whether this animal work is applicable to the human, we have sought to investigate whether the level of glucocorticoid receptors in circulating lymphocytes of children with the fetal hydantion syndrome (FHS) is as it is in the animals.We found that children with FHS had glucocorticoid receptor levels significantly elevated above those of unaffected children was also significantly levels significantly elevated above those of unaffected children with similar DPH exposure in control families. The receptor level of affected children was also significantly elevated above that of fathers of children with the FHS and of fathers and mothers of control children. These findings are consistent with those documented in the animal models and suggest that an elevated level of glucocorticoid receptors in lymphocytes may be a marker for suscept

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280308

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

年代:1987

数据来源: WILEY

摘要:

AbstractLissencephaly, hydrocephalus, and eye abnormalities characterize patients with the Walker‐Warburg syndrome, an uncommon autosomal recessive condition. Encephaloceles occur in about 50% of patients. We describe the prenatal diagnosis of this condition based on the ultrasonographic findings of retinal detachment, hydrocephalus, and an encephalocele in a fetus not known to be at ris

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280309

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

年代:1987

数据来源: WILEY

摘要:

AbstractWe report on an Indian woman with a severe shortness of stature, absence of the distal ulnae, and a predominantly spondylometaphyseal skeletal dysplasia. The clinicoradiographic changes in this patient appear to represent a unique skeletal disorder.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280310

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

年代:1987

数据来源: WILEY

摘要:

AbstractWe present the expected recurrence risks to a sib of an affected proband under 4 simple 2‐locus epistatic models for various allele frequencies at both the disease locus and the epistatic locus. Four obvious epistatic models are considered: an autosomal recessive disease with both 1) dominant and 2) recessive masking by the epistatic locus, and an autosomal dominant disease again with both 3) dominant and 4) recessive masking. Expected recurrence risks to a sib of an affected proband and to a sib of an affected proband with another normal sib are presented in the absence of information on parental status. Similar risks are presented for the case where both parents are known to be phenotypically normal. These recurrence risks were calculated using a convenient matrix notation which allows sequential calculation of genotypic probabilities. In general, 2‐locus epistatic models can give surprisingly low recurrence risks, and often these risks, especially for models of recessive diseases, fall into the range associated with a more general multifactorial model for liabil

ISSN:0148-7299    

DOI:10.1002/ajmg.1320280311

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

年代:1987

数据来源: WILEY