-
Annals of Medicine 2007Congenital diaphragmatic hernia (CDH) is a severe birth defect that is accompanied by malformations of the lung, heart, testis, and other organs. Patients with CDH may... (Review)
Review
Congenital diaphragmatic hernia (CDH) is a severe birth defect that is accompanied by malformations of the lung, heart, testis, and other organs. Patients with CDH may have any combination of these extradiaphragmatic defects, suggesting that CDH is often a manifestation of a global embryopathy. This review highlights recent advances in human and mouse genetics that have led to the identification of genes involved in CDH. These include genes for transcription factors, molecules involved in cell migration, and extracellular matrix components. The expression patterns of these genes in the developing embryo suggest that mesenchymal cell function is compromised in the diaphragm and other affected organs in patients with CDH. We discuss potential mechanisms underlying the seemingly random combination of diaphragmatic, pulmonary, cardiovascular, and gonadal defects in these patients.
Topics: Animals; Congenital Abnormalities; Diaphragm; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Humans; Infant, Newborn; Mice; Mutation; Transcription Factors
PubMed: 17558598
DOI: 10.1080/07853890701326883 -
Journal of Medical Genetics Jul 1988Many inborn errors of metabolism are associated with dysmorphic manifestations. In this review, we have attempted to correlate the dysmorphic features with the... (Review)
Review
Many inborn errors of metabolism are associated with dysmorphic manifestations. In this review, we have attempted to correlate the dysmorphic features with the underlying metabolic defect or its consequences. Most of the defects which we have discussed affect the synthesis or degradation of macromolecules (for example, collagen, elastin, bone mineral, proteoglycans, glycoproteins, and triglycerides). Such defects may affect either a single enzyme or multiple enzymes in specific organelles, such as lysosomes or peroxisomes, or they may affect hormonal control of synthesis and degradation. Examples are also included of defects affecting the catabolism of simple molecules when accumulating metabolites have a secondary effect on macromolecules, as in homocystinuria. In a number of instances, however, the correlation between the biochemical abnormality and the dysmorphic features are not understood. Ultimately, all dysmorphic syndromes will be attributable to a biochemical defect or its effects. The aim of this overview is to provide an insight into the relationship between the two at the present time.
Topics: Congenital Abnormalities; Humans; Lysosomes; Metabolism, Inborn Errors; Microbodies; Syndrome
PubMed: 3050094
DOI: 10.1136/jmg.25.7.463 -
Current Opinion in Obstetrics &... Apr 2011Evaluation of copy number variation by microarray analysis has significant advantages over standard metaphase karyotyping and is quickly becoming the primary means of... (Review)
Review
PURPOSE OF REVIEW
Evaluation of copy number variation by microarray analysis has significant advantages over standard metaphase karyotyping and is quickly becoming the primary means of postnatal genetic evaluation for neonates and infants with dysmorphic features or cognitive difficulties. Before this technology is routinely used for prenatal diagnosis, further evaluation of its value and the clinical dilemmas it may introduce requires further study. This article reviews the recent literature on array technology use in prenatal diagnosis.
RECENT FINDINGS
The use of microarray analysis for routine prenatal diagnosis is still being investigated. Use in certain prenatal situations such as the fetus with structural anomalies or those who are stillborn appears to add important, clinically relevant information. There are a broad range of array designs available and recent research has focused on the appropriate design for prenatal testing. Patient counseling may occasionally be difficult because of the uncertain phenotype associated with some array findings.
SUMMARY
We present a brief overview of microarray technology including benefits and limitations. Previous research regarding use of microarray in prenatal diagnosis including specific scenarios of anomalous fetuses and abnormal karyotype is reviewed. Current guidelines and the authors' recommendations are presented.
Topics: Chromosome Aberrations; Cognition Disorders; Congenital Abnormalities; Cytogenetics; Female; Genetic Counseling; Genetic Markers; Humans; Karyotyping; Models, Genetic; Oligonucleotide Array Sequence Analysis; Phenotype; Polymorphism, Single Nucleotide; Pregnancy; Prenatal Diagnosis; Translocation, Genetic
PubMed: 21297472
DOI: 10.1097/GCO.0b013e32834457c7 -
Journal of Perinatal Medicine Nov 2018
Topics: Aneuploidy; Congenital Abnormalities; Female; Humans; Pregnancy; Prenatal Diagnosis
PubMed: 30422803
DOI: 10.1515/jpm-2018-0333 -
The Israel Medical Association Journal... Jan 2009Renal tubular dysgenesis is a rare lethal kidney abnormality clinically manifested by olighydramnios, anuria and respiratory distress. Most of the information on this... (Comparative Study)
Comparative Study Review
BACKGROUND
Renal tubular dysgenesis is a rare lethal kidney abnormality clinically manifested by olighydramnios, anuria and respiratory distress. Most of the information on this entity is provided by case reports and short series.
OBJECTIVES
To evaluate the incidence and comparative frequency of clinical manifestations in different etiologic-pathogenic variants of RTD in Israel and in summarized published data.
METHODS
Stillborn and neonatal autopsy material from nine medical centers in northern and central Israel was studied. Information concerning pregnancy, labor and postnatal status and autopsy findings of cases with histologically, histochemically and immunohistochemically confirmed RTD were obtained from corresponding reports and from published material.
RESULTS
From the 1538 autopsies of fetuses (2 20 weeks gestation) and neonates that were performed between 1976 and 2007 we identified 12 cases of RTD (0.78%). Abnormality occurred more often (1.4%) in the Upper and Western Galilee than in Israel as a whole.
CONCLUSIONS
Our study and a review of the literature showed that the autosomal recessive variant of RTD was more frequent than twin-twin transfusion-induced. Most symptoms were similar in all variants of RTD, but their frequency was different in each of them.
Topics: Anuria; Autopsy; Congenital Abnormalities; Female; Humans; Incidence; Infant, Newborn; Israel; Kidney Tubules; Male; Oligohydramnios; Pregnancy; Respiratory Distress Syndrome, Newborn; Risk Factors
PubMed: 19344005
DOI: No ID Found -
Fertility and Sterility Oct 2016
Topics: 46, XX Disorders of Sex Development; Abnormalities, Multiple; Congenital Abnormalities; Humans; Mullerian Ducts; Syndrome; Uterus; Vagina
PubMed: 27430204
DOI: 10.1016/j.fertnstert.2016.06.033 -
American Journal of Medical Genetics.... Nov 2009Joubert syndrome (JBTS; OMIM 213300) is a rare, autosomal recessive disorder characterized by a specific congenital malformation of the hindbrain and a broad spectrum of... (Review)
Review
Joubert syndrome (JBTS; OMIM 213300) is a rare, autosomal recessive disorder characterized by a specific congenital malformation of the hindbrain and a broad spectrum of other phenotypic findings that is now known to be caused by defects in the structure and/or function of the primary cilium. The complex hindbrain malformation that is characteristic of JBTS can be identified on axial magnetic resonance imaging and is known as the molar tooth sign (MTS); other diagnostic criteria include intellectual disability, hypotonia, and often, abnormal respiratory pattern and/or abnormal eye movements. In addition, a broad spectrum of other anomalies characterize Joubert syndrome and related disorders (JSRD), and may include retinal dystrophy, ocular coloboma, oral frenulae and tongue tumors, polydactyly, cystic renal disease (including cystic dysplasia or juvenile nephronophthisis), and congenital hepatic fibrosis. The clinical course can be variable, but most children with this condition survive infancy to reach adulthood. At least eight genes cause JSRD, with some genotype-phenotype correlations emerging, including the association between mutations in the MKS3 gene and hepatic fibrosis characteristic of the JSRD subtype known as COACH syndrome. Several of the causative genes for JSRD are implicated in other ciliary disorders, such as juvenile nephronophthisis and Meckel syndrome, illustrating the close association between these conditions and their overlapping clinical features that reflect a shared etiology involving the primary cilium.
Topics: Abnormalities, Multiple; Adolescent; Brain; Child; Child, Preschool; Cilia; Ciliary Motility Disorders; Congenital Abnormalities; Developmental Disabilities; Female; Genes, Recessive; Genotype; Humans; Infant; Male; Pregnancy; Prenatal Diagnosis; Syndrome
PubMed: 19876931
DOI: 10.1002/ajmg.c.30229 -
BMC Medical Genomics Oct 2023Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of...
BACKGROUND
Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of prenatal WES and to investigate the pathogenic variants in structurally abnormal fetuses.
METHODS
We recruited 144 fetuses with structural anomalies between 14 and 2020 and 15 December 2021 in the study. Genetic screening was performed by WES combined with karyotyping and chromosomal microarray analysis. The molecular diagnostic yield of prenatal WES for each type of fetal structural anomaly and the identified pathogenic genes and mutations were reported.
RESULTS
In this study, we retrospectively analyzed the clinical and genetic data of 145 structurally anomalous fetuses. These cases were classified into 9 phenotypic classes based on antenatal ultrasound findings. Thirty-eight pathogenic variants in 24 genes were identified in 35 of the 145 cases, including 14 novel variants in 13 genes (EP300, MYH3, TSC2, MMP9, CPLANE1, INVS, COL1A1, EYA1, TTC21B, MKS1, COL11A2, PDHA1 and L1CAM). Five additional pathogenic variants were classified as incidental findings. Our study showed that the overall diagnosis rate of WES was 28.1% (27/96) in the parent-fetus trio cases and 16.3% (8/49) in the proband-only cases. Fetuses with musculoskeletal anomalies had the highest diagnostic yield (51.4%, 19/37). In addition, FGFR3 and COL1A1 were the most common pathogenic genes.
CONCLUSIONS
Our work expands the mutation spectrum of the genes associated with fetal structural anomalies and provides valuable information for future parental genetic counselling and pregnancy management of the structurally anomalous fetuses.
Topics: Female; Humans; Pregnancy; East Asian People; Exome Sequencing; Fetus; Pregnancy Trimester, First; Prenatal Diagnosis; Retrospective Studies; Ultrasonography, Prenatal; Congenital Abnormalities
PubMed: 37880672
DOI: 10.1186/s12920-023-01697-3 -
BMC Pregnancy and Childbirth Dec 2022The detection of an abnormality during prenatal screening implies that the parents are informed about possible treatment and management of the pregnancy, birth, and...
Parental information about the option to apply for pregnancy termination after the detection of a congenital abnormality and factors influencing parental decision-making: a cohort study.
BACKGROUND
The detection of an abnormality during prenatal screening implies that the parents are informed about possible treatment and management of the pregnancy, birth, and postnatal course. This information should enable the parents to make decisions regarding the pregnancy, especially in cases where termination of pregnancy may be an option. The objectives of this study were to investigate how often doctors informed parents about pregnancy termination when the fetus had an anomaly and which demographic factors were related to parental decision-making.
METHODS
This was a retrospective cohort study with prospectively collected data of fetuses diagnosed with an abnormality during prenatal screening between 2014 and 2016 in Denmark. We categorized the abnormalities into five long-term prognosis groups and analyzed their association with the doctor provided information about termination. We tested the association between demographic variables and parental decisions using univariate and multivariate statistical analyses.
RESULTS
Three hundred and twenty fetuses were diagnosed with an abnormality. In 67% of these cases, the parents were informed about termination. All parents whose fetus had a lethal prognosis were informed about termination. By comparison, the parents of 98% of fetuses with genetic disorders, 96% of fetuses with poor prognosis, 69% of fetuses with uncertain prognosis, and 12% of fetuses with good prognosis were informed about termination. Of these parents, 92% chose to terminate. A lethal long-term prognosis was the only factor related to parental decision to terminate a pregnancy.
CONCLUSIONS
Doctors mainly informed parents about the option of pregnancy termination for conditions with a poor or lethal long-term prognosis or for genetic disorders. Only conditions with a lethal prognosis were significantly related to the parental decision to terminate the pregnancy.
Topics: Pregnancy; Female; Humans; Cohort Studies; Retrospective Studies; Decision Making; Abortion, Induced; Prenatal Diagnosis; Parents; Congenital Abnormalities
PubMed: 36528557
DOI: 10.1186/s12884-022-05255-0 -
European Review For Medical and... Feb 2019To investigate the effect of intestinal flora on the neural development of severe hyperbilirubinemia neonates.
OBJECTIVE
To investigate the effect of intestinal flora on the neural development of severe hyperbilirubinemia neonates.
PATIENTS AND METHODS
The clinical data of 108 severe hyperbilirubinemia neonates admitted to the Dezhou People's Hospital from January 2015 through January 2018 were analyzed, and all newborns had a serum total bilirubin level > 342 μmol/L. Based on whether they suffered from neural development abnormalities, the neonatal patients were divided into the neural abnormality group (n=52) and the non-neural abnormality group (n=56). The unconjugated bilirubin levels in serum and cerebrospinal fluid (CSF) and the composition of intestinal flora were compared.
RESULTS
Among 108 neonates, there were 55 cases with developmental abnormalities, in which 52 (48.13%) cases had neural developmental abnormalities, mainly epileptic patients. The serum and CSF unconjugated bilirubin levels of the neonatal patients in the neural abnormality group were (466.25±97.64) μmol/L and (9.64±2.98) μmol/L, respectively, which were higher than those in neonatal patients of the non-neural abnormality group [(357.89±72.53) μmol/L and (6.73±3.11) μmol/L], with statistically significant differences (p<0.05). The abundance of intestinal flora genus in the neonates in the neural abnormality group was lower than that in the non-neural abnormality group, and the comparisons of Fusobacterium, Catabacter, Succinivibrio, Clostridium and Bacteroides between the two groups showed statistically significant differences (p<0.05).
DISCUSSION
The intestinal micro-ecological environment of newborns was vulnerable and easily affected by many factors such as methods of delivery, feeding ways and eating habits of their mothers. This study investigated the effects of intestinal flora on the neural development of neonates with severe hyperbilirubinemia. The results showed that, due to decreased intestinal flora diversity, the serum and cerebrospinal fluid bilirubin levels were elevated, and the abnormal rate of neural development was increased.
CONCLUSIONS
Severe hyperbilirubinemia neonates with neural abnormalities have decreased diversity of intestinal flora genus and relatively high serum and CSF bilirubin levels, probably because the decrease in the diversity of intestinal flora genus leads to the change of the blood-CSF barrier permeability, leading to raised levels of bilirubin in serum and CSF, thus affecting the neural development of neonatal patients.
Topics: Bilirubin; Congenital Abnormalities; Feces; Female; Gastrointestinal Microbiome; Humans; Hyperbilirubinemia, Neonatal; Infant, Newborn; Male; Nervous System; Retrospective Studies
PubMed: 30779098
DOI: 10.26355/eurrev_201902_17024