-
Taiwanese Journal of Obstetrics &... Mar 2020Anomalies in the müllerian ducts are congenital alterations with more prevalence than it is imagined, varying from 0.5 to 6.7% in the general population and up to 16.7%... (Review)
Review
Anomalies in the müllerian ducts are congenital alterations with more prevalence than it is imagined, varying from 0.5 to 6.7% in the general population and up to 16.7% in women with recurrent miscarriage. The main findings are primary amenorrhea, dysmenorrhea, pelvic pain, endometriosis, sexual difficulties and low self-esteem. The major impact on the quality of life in women stricken by these problems justifies this study, whose objective is to analyze their most important aspects such as etiopathogeny, classification, diagnostic methods and proposed treatments. The research was performed on the Medline-PubMed database from 1904 to 2018. The American Fertility Society, European Society of Human Reproduction and Embryology, and the European Society of Gynaecological Endoscopy classify malformations as: Class 1/U5bC4V4: agenesis or hypoplasia of uterus and vagina; Class 1/U5aC4V4: cervical hypoplasia, associated with total or partial vaginal agenesis; Class 2/U4: unicornuate uterus; Class 3/U3bC2V1 or Class3/U3bC2V2: uterus didelphys; Class 4/U3C0: bicornuate uterus; Class 5/U2: septate uterus; Class 6: arcuate uterus; Class 7/U1: induced by diethylstilbestrol, represented by a T-shaped uterus; and V3: transverse vaginal septum. The diagnostic methods are the two-dimensional or three-dimensional ultrasound, MRI, hysterosalpingo-contrast-sonography, X-ray hysterosalpingography, hysteroscopy and laparoscopy. Some müllerian malformations are healed with surgery and/or self-dilatation. For vaginal agenesis, dilatation by Frank technique shows good results while malformations with obstruction of the menstrual flow need to be rapidly treated by surgery.
Topics: Adult; Congenital Abnormalities; Dysmenorrhea; Endometriosis; Female; Humans; Hysterosalpingography; Hysteroscopy; Laparoscopy; Magnetic Resonance Imaging; Mullerian Ducts; Pelvic Pain; Pregnancy; Sexual Dysfunction, Physiological; Ultrasonography; Urogenital Abnormalities; Uterus; Vagina
PubMed: 32127135
DOI: 10.1016/j.tjog.2020.01.003 -
The Journal of International Advanced... Aug 2019The aim of this report is to provide international recommendations for functional ear reconstruction in patients with microtia and aural atresia. All patients with...
The aim of this report is to provide international recommendations for functional ear reconstruction in patients with microtia and aural atresia. All patients with microtia and external auditory atresia should be seen in the setting of a multidisciplinary team and agreed treatment outcomes should be measured, so that techniques, approaches, and results can be compared. The methods are expert opinion from the members of the International Microtia and Atresia Workgroup (IMAW). The consensus recommendations reported herein take into account the variability in practice patterns present among experts in the field; the degree of consensus was quantified by presenting the percentage of above authors who agree or partially agree with each statement. Recommendations include the definition and classification of microtia/atresia, treatment of microtia, treatment of congenital aural atresia, flowchart of functional ear reconstruction, and future research directions. Patients with microtia and aural atresia can be guided by the consensus recommendations provided herein.
Topics: Child; Child, Preschool; Congenital Abnormalities; Congenital Microtia; Constriction, Pathologic; Ear; Ear, External; Ear, Middle; Humans; Plastic Surgery Procedures; Treatment Outcome
PubMed: 31418720
DOI: 10.5152/iao.2019.7383 -
Lancet (London, England) Feb 2019Fetal structural anomalies, which are detected by ultrasonography, have a range of genetic causes, including chromosomal aneuploidy, copy number variations (CNVs; which...
BACKGROUND
Fetal structural anomalies, which are detected by ultrasonography, have a range of genetic causes, including chromosomal aneuploidy, copy number variations (CNVs; which are detectable by chromosomal microarrays), and pathogenic sequence variants in developmental genes. Testing for aneuploidy and CNVs is routine during the investigation of fetal structural anomalies, but there is little information on the clinical usefulness of genome-wide next-generation sequencing in the prenatal setting. We therefore aimed to evaluate the proportion of fetuses with structural abnormalities that had identifiable variants in genes associated with developmental disorders when assessed with whole-exome sequencing (WES).
METHODS
In this prospective cohort study, two groups in Birmingham and London recruited patients from 34 fetal medicine units in England and Scotland. We used whole-exome sequencing (WES) to evaluate the presence of genetic variants in developmental disorder genes (diagnostic genetic variants) in a cohort of fetuses with structural anomalies and samples from their parents, after exclusion of aneuploidy and large CNVs. Women were eligible for inclusion if they were undergoing invasive testing for identified nuchal translucency or structural anomalies in their fetus, as detected by ultrasound after 11 weeks of gestation. The partners of these women also had to consent to participate. Sequencing results were interpreted with a targeted virtual gene panel for developmental disorders that comprised 1628 genes. Genetic results related to fetal structural anomaly phenotypes were then validated and reported postnatally. The primary endpoint, which was assessed in all fetuses, was the detection of diagnostic genetic variants considered to have caused the fetal developmental anomaly.
FINDINGS
The cohort was recruited between Oct 22, 2014, and June 29, 2017, and clinical data were collected until March 31, 2018. After exclusion of fetuses with aneuploidy and CNVs, 610 fetuses with structural anomalies and 1202 matched parental samples (analysed as 596 fetus-parental trios, including two sets of twins, and 14 fetus-parent dyads) were analysed by WES. After bioinformatic filtering and prioritisation according to allele frequency and effect on protein and inheritance pattern, 321 genetic variants (representing 255 potential diagnoses) were selected as potentially pathogenic genetic variants (diagnostic genetic variants), and these variants were reviewed by a multidisciplinary clinical review panel. A diagnostic genetic variant was identified in 52 (8·5%; 95% CI 6·4-11·0) of 610 fetuses assessed and an additional 24 (3·9%) fetuses had a variant of uncertain significance that had potential clinical usefulness. Detection of diagnostic genetic variants enabled us to distinguish between syndromic and non-syndromic fetal anomalies (eg, congenital heart disease only vs a syndrome with congenital heart disease and learning disability). Diagnostic genetic variants were present in 22 (15·4%) of 143 fetuses with multisystem anomalies (ie, more than one fetal structural anomaly), nine (11·1%) of 81 fetuses with cardiac anomalies, and ten (15·4%) of 65 fetuses with skeletal anomalies; these phenotypes were most commonly associated with diagnostic variants. However, diagnostic genetic variants were least common in fetuses with isolated increased nuchal translucency (≥4·0 mm) in the first trimester (in three [3·2%] of 93 fetuses).
INTERPRETATION
WES facilitates genetic diagnosis of fetal structural anomalies, which enables more accurate predictions of fetal prognosis and risk of recurrence in future pregnancies. However, the overall detection of diagnostic genetic variants in a prospectively ascertained cohort with a broad range of fetal structural anomalies is lower than that suggested by previous smaller-scale studies of fewer phenotypes. WES improved the identification of genetic disorders in fetuses with structural abnormalities; however, before clinical implementation, careful consideration should be given to case selection to maximise clinical usefulness.
FUNDING
UK Department of Health and Social Care and The Wellcome Trust.
Topics: Abnormal Karyotype; Abortion, Eugenic; Abortion, Spontaneous; Congenital Abnormalities; DNA Copy Number Variations; Female; Fetal Development; Fetus; Humans; Infant, Newborn; Live Birth; Male; Nuchal Translucency Measurement; Parents; Perinatal Death; Pregnancy; Prospective Studies; Stillbirth; Exome Sequencing
PubMed: 30712880
DOI: 10.1016/S0140-6736(18)31940-8 -
Current Biology : CB May 2022Interview with John Wallingford, who studies the cell biology of embryonic morphogenesis and the genetics of human birth defects at the University of Texas at Austin.
Interview with John Wallingford, who studies the cell biology of embryonic morphogenesis and the genetics of human birth defects at the University of Texas at Austin.
Topics: Congenital Abnormalities; Embryonic Development; Humans
PubMed: 35609534
DOI: 10.1016/j.cub.2022.04.050 -
Ultrasound in Obstetrics & Gynecology :... Oct 2019To examine the performance of the routine 11-13-week scan in detecting fetal non-chromosomal abnormalities.
OBJECTIVE
To examine the performance of the routine 11-13-week scan in detecting fetal non-chromosomal abnormalities.
METHODS
This was a retrospective study of prospectively collected data from 100 997 singleton pregnancies attending for a routine ultrasound examination of fetal anatomy, performed according to a standardized protocol, at 11-13 weeks' gestation. All continuing pregnancies had an additional scan at 18-24 weeks and 71 754 had a scan at either 30-34 or 35-37 weeks. The final diagnosis of fetal abnormality was based on the results of postnatal examination in cases of live birth and on the findings of the last ultrasound examination in cases of pregnancy termination, miscarriage or stillbirth. The performance of the 11-13-week scan in the detection of fetal abnormalities was determined.
RESULTS
The study population contained 1720 (1.7%) pregnancies with a fetal abnormality, including 474 (27.6%) detected on the first-trimester scan, 926 (53.8%) detected on the second-trimester scan and 320 (18.6%) detected in the third trimester or postnatally. At 11-13 weeks' gestation, we diagnosed all cases of acrania, alobar holoprosencephaly, encephalocele, tricuspid or pulmonary atresia, pentalogy of Cantrell, ectopia cordis, exomphalos, gastroschisis and body-stalk anomaly and > 50% of cases of open spina bifida, hypoplastic left heart syndrome, atrioventricular septal defect, complex heart defect, left atrial isomerism (interrupted inferior vena cava with normal intracardiac anatomy), lower urinary tract obstruction, absence of extremities, fetal akinesia deformation sequence and lethal skeletal dysplasia. Common abnormalities that were detected in < 10% of cases at 11-13 weeks included ventriculomegaly, agenesis of the corpus callosum, isolated cleft lip, congenital pulmonary airway malformation, ventricular septal defect, abdominal cysts, unilateral renal agenesis or multicystic kidney, hydronephrosis, duplex kidney, hypospadias and talipes.
CONCLUSIONS
A routine 11-13-week scan, carried out according to a standardized protocol, can identify many severe non-chromosomal fetal abnormalities. A summary statistic of the performance of the first-trimester scan is futile because some abnormalities are always detectable, whereas others are either non-detectable or sometimes detectable. To maximize prenatal detection of abnormalities, additional scans in both the second and third trimesters are necessary. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adult; Congenital Abnormalities; Female; Fetus; Gestational Age; Humans; Nuchal Translucency Measurement; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Prenatal Care; Retrospective Studies; Ultrasonography, Prenatal
PubMed: 31408229
DOI: 10.1002/uog.20844 -
European Journal of Pediatrics Mar 2018Congenital portosystemic venous shunts are rare developmental anomalies resulting in diversion of portal flow to the systemic circulation and have been divided into... (Review)
Review
UNLABELLED
Congenital portosystemic venous shunts are rare developmental anomalies resulting in diversion of portal flow to the systemic circulation and have been divided into extra- and intrahepatic shunts. They occur during liver and systemic venous vascular embryogenesis and are associated with other congenital abnormalities. They carry a higher risk of benign and malignant liver tumors and, if left untreated, can result in significant medical complications including systemic encephalopathy and pulmonary hypertension.
CONCLUSION
This article reviews the various types of congenital portosystemic shunts and their anatomy, pathogenesis, symptomatology, and timing and options of treatment. What is Known: • The natural history and basic management of this rare congenital anomaly are presented. What is New: • This paper is a comprehensive review; highlights important topics in pathogenesis, clinical symptomatology, and treatment options; and proposes an algorithm in the management of congenital portosystemic shunt disease in order to provide a clear idea to a pediatrician. An effort has been made to emphasize the indications for treatment in the children population and link to the adult group by discussing the consequences of lack of treatment or delayed diagnosis.
Topics: Abnormalities, Multiple; Endovascular Procedures; Hepatectomy; Humans; Ligation; Liver Transplantation; Portal Vein; Vascular Malformations
PubMed: 29243189
DOI: 10.1007/s00431-017-3058-x -
Taiwanese Journal of Obstetrics &... May 2021Third trimester ultrasound has long been in obstetrics a topic of debate. This issue is framed in a historical debate on the effectiveness of routine obstetrical... (Review)
Review
Third trimester ultrasound has long been in obstetrics a topic of debate. This issue is framed in a historical debate on the effectiveness of routine obstetrical ultrasound and two opposing trends originated in America and Europe, respectively. Primary function of this ultrasound has been to detect fetal growth restriction, but no study has shown evidence of improving perinatal outcomes. Other secondary functions are detection of fetal abnormalities or evaluation of fetal presentation, and they have also shown no evidence. Despite the continuous appearance of works in this regard, health policies of both american and european trends have not been modified. Future seems to show a prolongation of the stalemate. Those health systems with a universal third trimester policy should propose an optimization of the test, in order to improve the benefits and obtain data for future studies that could resolve this longstanding debate.
Topics: Congenital Abnormalities; Europe; Female; Fetal Growth Retardation; Humans; Obstetrics; Pregnancy; Pregnancy Trimester, Third; Ultrasonography, Prenatal; United States
PubMed: 33966720
DOI: 10.1016/j.tjog.2021.03.004 -
American Journal of Medical Genetics.... May 2017Craniosynostosis, the premature ossification of one or more skull sutures, is a clinically and genetically heterogeneous congenital anomaly affecting approximately one... (Review)
Review
Craniosynostosis, the premature ossification of one or more skull sutures, is a clinically and genetically heterogeneous congenital anomaly affecting approximately one in 2,500 live births. In most cases, it occurs as an isolated congenital anomaly, that is, nonsyndromic craniosynostosis (NCS), the genetic, and environmental causes of which remain largely unknown. Recent data suggest that, at least some of the midline NCS cases may be explained by two loci inheritance. In approximately 25-30% of patients, craniosynostosis presents as a feature of a genetic syndrome due to chromosomal defects or mutations in genes within interconnected signaling pathways. The aim of this review is to provide a detailed and comprehensive update on the genetic and environmental factors associated with NCS, integrating the scientific findings achieved during the last decade. Focus on the neurodevelopmental, imaging, and treatment aspects of NCS is also provided.
Topics: Congenital Abnormalities; Cranial Sutures; Craniosynostoses; Humans; Ossification, Heterotopic; Phenotype
PubMed: 28160402
DOI: 10.1002/ajmg.a.38159 -
Ugeskrift For Laeger Mar 2017Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital anomaly characterized by uterovaginal agenesis in females with normal secondary sex characteristics and... (Review)
Review
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital anomaly characterized by uterovaginal agenesis in females with normal secondary sex characteristics and normal karyotype (46,XX). The prevalence of MRKH syndrome is one in 5,000 live female births as recently confirmed by a nationwide population-based study in Denmark. This review kaleidoscopically summarizes the current knowledge of the history, genetics, diagnostics, treatment of vaginal agenesis, psychosexual aspects, and fertility options in MRKH syndrome.
Topics: 46, XX Disorders of Sex Development; Congenital Abnormalities; Female; Humans; Infertility, Female; Magnetic Resonance Imaging; Mullerian Ducts
PubMed: 28397650
DOI: No ID Found -
Acta Obstetricia Et Gynecologica... Jun 2021Claims of medical negligence are universal. Unexpected adverse pregnancy outcome may trigger litigation. Such outcomes, especially with neurodevelopmental sequelae, may...
INTRODUCTION
Claims of medical negligence are universal. Unexpected adverse pregnancy outcome may trigger litigation. Such outcomes, especially with neurodevelopmental sequelae, may be compounded by a genetic disorder, congenital abnormality, or syndrome.
MATERIAL AND METHODS
This is a report of 297 cases in which a pregnancy complication, error, or incident occurred that was followed by progeny with a genetic disorder, congenital abnormality, or syndrome that spawned litigation. The author assessed, opined, and in many cases, testified about causation.
RESULTS
Pregnancies complicated by hypoxic ischemic encephalopathy were not infrequently compounded by offspring with a genetic disorder, congenital abnormality, or syndrome. Multiple cases were brought because of missed ultrasound or laboratory diagnoses, or failures in carrier detection. Teratogenic medication prescribed before or during pregnancy invited legal purview. Failure to refer (or confer) for genetic evaluation or counseling in the face of significant risk, occurred repeatedly. Ethical breaches and hubris promptly led to litigation.
CONCLUSIONS
Many lessons and recommendations emerge in this report. These include the realization that the vast majority of errors in this series involved at least two caregivers, serial ultrasound studies are important, decreased fetal movements may signal a genetic disorder, congenital abnormality, or syndrome, family history and ethnicity are vital, cognitive biases profoundly affect decision-making. Finally, the simplest of errors have the potential for causing life-long grief.
Topics: Adult; Congenital Abnormalities; Female; Humans; Liability, Legal; Malpractice; Medical Errors; Obstetrics; Patient Safety; Pregnancy; Pregnancy Complications
PubMed: 33483959
DOI: 10.1111/aogs.14095