ABSTRACT
OBJECTIVE: The aberrant right subclavian artery is a malformation of the aortic arch present at less than 2 % of the individuals in the general population. This incidence is higher in trisomy 21, making it possible use the aberrant right subclavian artery as a prenatal marker of trisomy 21. MATERIAL AND METHODS: This work, which relates to a series of 11,479 consecutive fetal autopsies aims to measure the force of association between the aberrant right subclavian artery and trisomy 21, to confront our results with the sonographic series previously published and to contribute to assess the place that can have this sign in the echographic screening and the fetopathologic diagnosis of trisomy 21. RESULTS: The isolated presence of an aberrant right subclavian artery does not represent an argument sufficient for the indication of a karyotype. But the detection of this anomaly must make pay a special attention in search of other associated signs. CONCLUSION: On the results of this study, the aberrant right subclavian artery has to be considered as a part of the spectrum not only of trisomy 21, but also of many other congenital syndromes.
Subject(s)
Aneurysm/complications , Cardiovascular Abnormalities/complications , Deglutition Disorders/complications , Down Syndrome/complications , Subclavian Artery/abnormalities , Ultrasonography, Prenatal , Aneurysm/diagnostic imaging , Aneurysm/genetics , Cardiovascular Abnormalities/diagnostic imaging , Cardiovascular Abnormalities/genetics , Deglutition Disorders/diagnostic imaging , Deglutition Disorders/genetics , Down Syndrome/diagnostic imaging , Female , Humans , Pregnancy , Retrospective Studies , Risk Factors , Subclavian Artery/diagnostic imagingABSTRACT
OBJECTIVE: Hydatidiform moles, subdivided into partial moles (PM) and complete moles (CM), are abnormal pregnancies with a disturbed invasive behavior. We had previously shown that MMP-2 and p53 proteins are overexpressed in CM versus PM, and that in primary cytotrophoblasts p53 protein is stabilized by complexing to the 78kDa glucose-regulated protein (GRP78) which is involved in cytotrophoblasts invasion process. The present study aims to compare the transcript expression profile of p53, MMP-2 and GRP78 in hydatidiform moles. METHODS: A retrospective study was performed by RT-qPCR and immunostaining on paraffin-embedded tissues of 19 PM, 16 CM and 16 control (CTRL) samples of gestational age 8-12 weeks. RESULTS: Expression of MMP-2 transcript was significantly overexpressed in CM compared to CTRL samples (p=0.031). In contrast, expression of p53 transcript was similar among the samples. This suggests a regulation of p53 in CM at the protein level. GRP78 cDNA was significantly overexpressed in CM compared to CTRL (p=0.021) and to PM (p=0.011). At the protein level, immunostaining of GRP78 was on average stronger in CM than PM samples. CONCLUSIONS: Collectively, present data suggest that in CM, p53 is normally expressed at the mRNA level but probably complexes at the protein level with the overexpressed GRP78, leading to accumulation of p53 protein. Moreover, since GRP78 and MMP-2 are increased in CM and known to play key roles in invasion, our results suggest that GRP78 and MMP-2 should be investigated as prognostic markers of hydatidiform moles.
Subject(s)
Heat-Shock Proteins/biosynthesis , Hydatidiform Mole/metabolism , Case-Control Studies , Endoplasmic Reticulum Chaperone BiP , Female , Heat-Shock Proteins/genetics , Humans , Hydatidiform Mole/genetics , Immunohistochemistry , Matrix Metalloproteinase 2/biosynthesis , Matrix Metalloproteinase 2/genetics , Paraffin Embedding , Pregnancy , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction/methods , Tumor Suppressor Protein p53/biosynthesis , Tumor Suppressor Protein p53/geneticsABSTRACT
Acute fatty liver of pregnancy (AFLP) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome are serious maternal illnesses occurring in the third trimester of pregnancy with significant perinatal and maternal mortality. AFLP may result from mitochondrial defects in the beta-oxidation of fatty acids, in particular a deficiency of the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) in the fetus. Clinical findings in AFLP vary and its diagnosis is complicated by a significant overlap in clinical and biochemical features with HELLP syndrome. We report the case of 2 siblings who died, the first one in the neonatal period of asphyxia with multivisceral presentation and the second one from sudden death at 7 months. Autopsy of the latter infant revealed hepatic steatosis associated with cardiomyopathy, which led to suspicion of a fatty acid oxidation deficiency. Mutation analysis demonstrated that both children were homozygous for the common mutation c.1528G>C and the parents were heterozygous for this same mutation. This case demonstrates the importance of screening mothers with acute fatty liver disease of pregnancy and their children at birth for a metabolic disease. This article proposes several metabolic tests for mother and child suspected of having beta-oxidation of a fatty acid disorder.
Subject(s)
Acyl-CoA Dehydrogenase, Long-Chain/deficiency , Fatty Liver/etiology , Fetal Diseases/diagnosis , HELLP Syndrome/etiology , Infant, Premature, Diseases/diagnosis , Multienzyme Complexes/genetics , Acyl-CoA Dehydrogenase, Long-Chain/genetics , Chromosome Aberrations , DNA Mutational Analysis , Fatal Outcome , Fatty Liver/genetics , Fatty Liver/pathology , Female , Fetal Diseases/genetics , Fetal Diseases/pathology , Genes, Recessive , HELLP Syndrome/genetics , HELLP Syndrome/pathology , Humans , Infant , Infant, Newborn , Infant, Premature, Diseases/genetics , Infant, Premature, Diseases/pathology , Male , Mitochondrial Trifunctional Protein , Pregnancy , Sudden Infant Death/pathologyABSTRACT
Elastic fibers are composed of microfibrils containing fibrillin-1 and an elastic component, elastin. Microfibrils may not be associated with elastin. In the adult liver, fibrillin-1 and elastin are coexpressed within the stroma and portal tracts vessel walls. Fibrillin-1 is expressed alone around the bile ducts and within the Disse space. There is little work that has studied the elastic fiber organization during the fÅtal liver development. Here, we studied the expression of fibrillin-1 and elastin by immunohistochemistry on 20 cases of fÅtal liver. During the development of the portal tract, the two components are coexpressed on interstitial elastic fibers and within vessel walls. Fibrillin-1 is expressed alone around the bile structures during their maturation. Unlike adult liver, fibrillin-1 is expressed on thin and very irregular microfibrils within the Disse space. Our study shows that the elastic matrix development in the portal tract follows the development of the different structures, notably biliary structures. In the Disse space, microfibrils are not continuous. Their maturation may be in relation with the change of the hepatic blood flow after birth.
Subject(s)
Elastic Tissue , Elastin/biosynthesis , Liver/embryology , Microfilament Proteins/biosynthesis , Elastin/analysis , Fibrillin-1 , Fibrillins , Humans , Immunohistochemistry , Liver/metabolism , Microfilament Proteins/analysisABSTRACT
The prognosis of autosomal recessive polycystic kidney disease is known to correlate with genotype. The presence of two truncating mutations in the PKHD1 gene encoding the fibrocystin protein is associated with neonatal death while patients who survive have at least one missense mutation. To determine relationships between genotype and renal and hepatic abnormalities we correlated the severity of renal and hepatic histological lesions to the type of PKHD1 mutations in 54 fetuses (medical pregnancy termination) and 20 neonates who died shortly after birth. Within this cohort, 55.5% of the mutations truncated fibrocystin. The severity of cortical collecting duct dilatations, cortical tubule and glomerular lesions, and renal cortical and hepatic portal fibrosis increased with gestational age. Severe genotypes, defined by two truncating mutations, were more frequent in patients of less than 30 weeks gestation compared to older fetuses and neonates. When adjusted to gestational age, the extension of collecting duct dilatation into the cortex and cortical tubule lesions, but not portal fibrosis, was more prevalent in patients with severe than in those with a non-severe genotype. Our results show the presence of two truncating mutations of the PKHD1 gene is associated with the most severe renal forms of prenatally detected autosomal recessive polycystic kidney disease. Their absence, however, does not guarantee survival to the neonatal period.
Subject(s)
Fetal Diseases/genetics , Fetal Diseases/pathology , Mutation , Polycystic Kidney, Autosomal Recessive/genetics , Polycystic Kidney, Autosomal Recessive/pathology , Receptors, Cell Surface/genetics , Genotype , Humans , Infant, Newborn , PhenotypeABSTRACT
Type II lissencephaly (type II LIS) is a group of autosomal recessive congenital muscular dystrophies (CMD) associated with defects in alpha-DG O-glycosylation, which comprises Walker-Warburg syndrome, Fukuyama cerebral and muscular dystrophy, or muscle-eye-brain disease. The most severe forms of these diseases often have a fetal presentation and lead to a pregnancy termination. We report here the first molecular study on fetal type II LIS in a series of 47 fetuses from 41 unrelated families. Sequencing of the different genes known to be involved in alpha-DG O-glycosylation allowed the molecular diagnosis in 22 families: involvement of POMT1 was demonstrated in 32% of cases, whereas POMGNT1 and POMT2 were incriminated in 15% and in 7% of cases, respectively. We found 30 different mutations in these three genes, 25 were described herein for the first time, 15 in POMT1, and five in POMT2 and POMGNT1. Despite sequencing of FKRP, FCMD, and LARGE, no definitive molecular diagnosis could be made for the other half of our cases. Preliminary results concerning genotype-phenotype correlations show that the choice of the first gene sequenced should depend on the clinical severity of the type II LIS; POMT1 and POMT2 for severest clinical picture and POMGNT1 for milder disease. The other genes, FKRP, FCMD, and LARGE, seem not to be implicated in the fetal form of CMD.
Subject(s)
Gene Expression Regulation , Muscular Dystrophies/embryology , Muscular Dystrophies/genetics , Alleles , Dystroglycans/metabolism , Female , Genotype , Gestational Age , Humans , Male , Mannosyltransferases/genetics , Microsatellite Repeats , Models, Genetic , Mutation , Phenotype , Polymorphism, Single NucleotideABSTRACT
UNLABELLED: SUBJECT. Massive Chronic Intervillositis is an infrequent inflammation lesion of the placenta, characterized by lymphohistiocytic intervillous infiltration, associated with fibrinoid deposition. The purpose of this study was to evaluate the perinatal outcome of pregnancies complicated by such lesions. MATERIAL AND METHODS: We conducted a descriptive retrospective multicentric analysis of a series of pregnancies for which placenta or products of abortion were analyzed between January 1995 and September 2005, at the University Hospital of Bordeaux. After re-examining the histology slides, we performed a semi-quantitative graduation of the cell infiltration and fibrinoid deposition. RESULTS: Twenty-five women were included (one twin-pregnancy and two histologic recurrences). We found three spontaneous abortions before 22 weeks, four intrauterine fetal deaths and three neonatals deaths. Seven of eight elective inductions pregnancies, were performed for intrauterine growth restriction less than 2.5 percentile. The rate of pregnancy loss was 55% and the perinatal mortality was 29%. 77% of fetuses are small for gestational age. Three mothers were pre-eclamptic. 21% of the fetuses had a congenital malformation. Only 32% of the fetuses were alive one week after birth. Histologically, 25% were associated with lesions of Villitis of Unknown Etiology. 77% of the cell infiltration was grade 3 and seemed to be correlated with severe growth restriction. We describe 3 cases of antenatal diagnosis of Chronic Intervillositis, realised after immunofixation on chorionic villous sampling. CONCLUSION: Massive Chronic Intervillositis is a recurrent lesion with a poor prognosis complicated by spontaneous abortion, intrauterine growth restriction and perinatal fetal death. Currently, there is no treatment. Chorionic villous sampling in severe growth restriction might be useful in order to obtain at the same time the fetal karyotype and an histological probe of the placenta.
Subject(s)
Chorioamnionitis/pathology , Chorionic Villi , Adult , Chronic Disease , Female , Humans , Pregnancy , Pregnancy Outcome , Prognosis , Retrospective StudiesABSTRACT
UNLABELLED: The deletion of chromosome 22q11.2 is involved in the majority of DiGeorge or velo-cardiofacial syndrome. The phenotypic variability was noted in the "CATCH 22" acronym. This acronym doesn't recapitulate the full spectrum of the symptoms. The diagnosis of this syndrome can be done with the prenatal diagnosis, with fetal pathology or with a child alive. METHODS: Review of 52 cases with the microdeletion 22q11. Six cases were diagnosed during the prenatal period, 12 cases at fetal pathology examination, and 34 cases during infancy. RESULTS: Cardiac malformations were the major indications (75%) to search for the microdeletion. The facial dysmorphy was difficult to diagnose during the antenatal period or in dead foetus, thereby it was not often recognized. The renal anomalies usually present in 35% of cases, were diagnosed in only 6 to 16% of the cases in our study. CONCLUSION: Phenotypic diversity of the DiGeorge syndrome is important. Its knowledge allows to better determine the indications of the research of the microdeletion. 22q11.2.
Subject(s)
DiGeorge Syndrome , Child , Chromosome Deletion , Chromosomes, Human, Pair 22/genetics , DiGeorge Syndrome/diagnosis , DiGeorge Syndrome/genetics , Female , Fetal Death/etiology , Fetal Death/genetics , Humans , In Situ Hybridization, Fluorescence , Infant, Newborn , Male , Phenotype , Pregnancy , Prenatal Diagnosis , Research , Retrospective StudiesABSTRACT
This manuscript reports a fetus of 24 weeks gestation, detected on echography to have congenital anomalies: intra-uterine growth retardation, facial dysmorphism, ventricular septal defect with aortic displacement and 8-mm nuchal skinfold thickness. Karyotype was performed. Post termination of pregnancy autopsy showed additionnal internal organ anomalies included: absent gall bladder and thyroid isthmus agenesis. To our knowledge, these anomalies have never been described in trisomic 22 fetuses. This case suggests that chromosome 22 could play a role in thyroid development.
Subject(s)
Chromosomes, Human, Pair 22/genetics , Gallbladder/abnormalities , Thyroid Gland/abnormalities , Trisomy/genetics , Centromere/genetics , Chromosome Aberrations , Female , Fetal Growth Retardation/genetics , Humans , In Situ Hybridization, Fluorescence , Male , Pregnancy , Pregnancy OutcomeABSTRACT
NDP kinases are the non-specific enzymes which catalyse the synthesis of the NTPs through a transfer reaction using ATP as phosphoryl donor. In addition to their enzymatic activity, they display other not yet explained functions related to cell growth, differentiation and apoptosis, embryonic development, tumour progression and metastasis. In this study, the expression patterns of the three highly related NDP kinases A, B and C isoforms were investigated in the developing human trophoblast. Both NDP kinase A and B were found to be primarily present in the villous and extravillous cytotrophoblasts, while NDP kinase C was found almost exclusively in the syncytiotrophoblast layer. This suggests that NDP kinase A and B could be a marker for the mononuclear stage of differentiation of villous trophoblasts, while NDP kinase C could be a marker of the syncytiotrophoblast layer.
Subject(s)
Gene Expression Regulation, Developmental/genetics , Nucleoside-Diphosphate Kinase/genetics , Trophoblasts/enzymology , Embryonic and Fetal Development/physiology , Eye Proteins/metabolism , Female , Gestational Age , Humans , Immunohistochemistry , In Situ Hybridization , Ki-67 Antigen/analysis , NM23 Nucleoside Diphosphate Kinases , Nerve Tissue Proteins/metabolism , Nucleoside-Diphosphate Kinase/metabolism , PregnancySubject(s)
Antibodies, Monoclonal/adverse effects , Antirheumatic Agents/adverse effects , Legionellosis/chemically induced , Aged , Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Female , Humans , Infliximab , Legionellosis/pathologyABSTRACT
Iniencephaly is a rare malformation of the base of the skull. The brain is involved and prognosis is almost invariably lethal. We identified 202 reports in the literature up through 2000. Ultrasound morphology explorations now provide the diagnosis making it possible to propose pregnancy termination. We report four cases of iniencephaly diagnosed between 1992 and 1999.
Subject(s)
Neural Tube Defects/diagnostic imaging , Abnormalities, Multiple/diagnostic imaging , Abortion, Therapeutic , Adult , Brain/abnormalities , Brain/pathology , Female , Humans , Infant, Newborn , Pregnancy , Retrospective Studies , Skull/abnormalities , Skull/pathology , Ultrasonography, PrenatalABSTRACT
Schizencephaly is a neuronal migration anomaly characterized by gray matter lined clefts extending from the ventricle to the cortical surface leading to specific lesions, well demonstrated by imaging. The lips of the clefts can be fused or separated. Prognosis is related to the extend of the involved cortex. Both genetic and acquired factors can be responsible for this pathology. Three cases of antenatal diagnosed open schizencephaly are reported. Two cases are unilateral and one is bilateral. A cerebral anomaly has been detected in all cases by routine ultrasonography (US) revealing a ventricular dilatation with cortical associated abnormalities. Prenatal magnetic resonance imaging (MRI) permitted the diagnosis in the 3 cases. All cases had led to abortion because of the importance of the cortical defect. The aim of this report is to point out the importance of fetal MRI in the diagnosis of migration disorder and to discuss the medical implications. Indeed, MRI is better suited than US for the prenatal diagnosis of schizencephaly, being able to detect normal and abnormal brain cellular migration, especially with fast imaging (HASTE sequences). With its multiplanar imaging capability, MRI demonstrates the cleft extending from the pial surface to the ventricular ependyma and thus provides characteristic diagnosis of this disorder. Moreover, ventricular dilatation, a frequent anomaly detected by US should be completed with MRI in order to research a neuronal migration disorder.
Subject(s)
Brain/abnormalities , Fetal Diseases/diagnosis , Magnetic Resonance Imaging , Prenatal Diagnosis , Cerebral Ventricles/pathology , Dilatation, Pathologic/diagnosis , Female , Humans , Pregnancy , Ultrasonography, PrenatalABSTRACT
Propionibacterium acnes is a weakly pathogenic commensal of the skin. When isolated from blood cultures it is often considered a contaminant. However, P. acnes may be responsible for severe infections and its role in certain cases of infectious endocarditis has now been definitely established.(1) We report a case of endocarditis due to P. acnes stemming from a ventricular patch and revealed by a gallium 67 scan.
Subject(s)
Endocarditis, Bacterial/diagnostic imaging , Endocarditis, Bacterial/microbiology , Gram-Positive Bacterial Infections/diagnostic imaging , Gram-Positive Bacterial Infections/microbiology , Propionibacterium acnes/isolation & purification , Gallium Radioisotopes , Humans , Male , Middle Aged , Radionuclide Imaging , Radiopharmaceuticals , Severity of Illness IndexABSTRACT
A case-control study was conducted to establish the source of a community outbreak of typhoid fever in Utelle, France, a village located in the Alpes-Maritimes district of the French Riviera. Thirteen confirmed cases of typhoid fever and 41 confirmed community controls were included in the study. Cases and controls did not differ regarding ingestion of water. Multivariate logistic regression analysis identified consumption of pork meats during a village festival as the only statistically significant risk factor for typhoid fever after adjusting for age and sex (odds ratio, 76.0; 95% confidence interval, 3.5-1660). Assessment of food-handling procedures at the inn where the food had been prepared showed that the refrigeration and cooking facilities were inadequate to maintain a proper sanitary environment during the preparation of a meal for 350 people. Although the exact cause of the epidemic could not be confirmed, food contaminated by a chronic typhi carrier is the most plausible hypothesis.
Subject(s)
Disease Outbreaks , Meat/microbiology , Typhoid Fever/epidemiology , Animals , Case-Control Studies , Female , Food Handling , Food Microbiology , France/epidemiology , Humans , Male , Regression Analysis , Salmonella typhi/classification , Salmonella typhi/isolation & purification , Swine , Typhoid Fever/transmissionABSTRACT
We found a new C-terminal amyloidogenic variant of apolipoprotein AI (apoAI), Leu178His in a French kindred, associated with cardiac and larynx amyloidosis and skin lesions with onset during the fourth decade. This single-point mutation in exon 4 of the apoAI gene was detected by DNA sequencing of polymerase chain reaction amplified material and restriction fragment length polymorphism analysis in two siblings. Blood, larynx, and skin biopsies were available from one sibling. Anti-apoAI immunoblotting of isoelectric focusing of plasma showed a +1 alteration in the charge of the protein. Extraction of fibrils from the skin biopsy revealed both full-length and N-terminal fragments of apoAI and transthyretin (TTR). ApoAI and TTR co-localized in amyloid deposits as demonstrated by immunohistochemistry. The present report, together with the first recently described C-terminal amyloidogenic variant of apoAI, Arg173Pro, shows that amyloidogenicity of apoAI is not a feature exclusive to N-terminal variants. The most striking characteristic of amyloid fibrils in Leu178His is that wild-type TTR is co-localized with apoAI in the fibrils. We have previously determined that a fraction of plasma TTR circulates in plasma bound to high-density lipoprotein and that this interaction occurs through binding to apoAI. Therefore we hypothesize that nonmutated TTR might influence deposition of apoAI as amyloid.
Subject(s)
Amyloid/metabolism , Amyloidosis/genetics , Apolipoprotein A-I/genetics , Apolipoprotein A-I/metabolism , Prealbumin/metabolism , Adult , Amino Acid Sequence/genetics , Amyloidosis/blood , Apolipoprotein A-I/blood , Base Sequence/genetics , Cholesterol/blood , Female , HumansABSTRACT
Cytomegalovirus is the most common cause of congenital viral infection. In utero this infection is usually suspected on the basis of ultrasound findings. We present a case in which routine ultrasound examination demonstrated a decrease in fetal cephalic dimensions at 32 weeks' gestation in an asymptomatic patient. Transvaginal ultrasound revealed echogenic vessels in the thalami and lesions in the subependymal region. Suspected diagnosis of fetal cytomegalovirus infection was confirmed by positive titers of anti-cytomegalovirus-IgM antibodies in fetal blood and amniotic-fluid PCR studies. Fetal cerebral MRI demonstrated parenchymal atrophy and polymicrogyria. The parents decided to terminate the pregnancy, and necropsy confirmed the diagnosis. Suspicion of CMV fetal infection should prompt transvaginal ultrasound and fetal brain MRI.
Subject(s)
Brain/embryology , Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/diagnosis , Fetal Diseases/virology , Magnetic Resonance Imaging , Ultrasonography, Prenatal , Adult , Brain/pathology , Cytomegalovirus Infections/diagnostic imaging , Female , Fetal Diseases/diagnosis , Gestational Age , Humans , PregnancyABSTRACT
Splenogonadal fusion (SGF) is a rare congenital malformation in which the spleen is abnormally connected to the gonad. SGF may occur as an isolated condition or may be associated with other malformations, especially with terminal limb defects in what is called splenogonadal fusion limb defect (SGFLD) syndrome. In this article, we report on 5 new cases of SGFLD and we review the 25 cases reported since 1889. Most cases reviewed here have a combination of severe limb and oro-mandibular defects, suggesting that SGFLD may be related to the broader group of Hanhart complex. In addition, several cases have limb malformations and facial anomalies, which suggest that SGFLD overlaps with both femur-fibula-ulna dysostosis and femoral-facial syndrome. The hypothesis of a vascular disruptive event, occurring between the 5th and the 7th weeks of gestation, could explain the limb defects, the mandibular hypoplasia, and the fusion of the spleen to the gonad observed in SGFLD. However, this heterogenous and polytopic condition could also be the consequence of a primary field defect. All the cases to date reported have been sporadic and the recurrence risk is probably low. However, a recent case of Roberts syndrome with SGF was reported that suggests careful examination of chromosomal status.