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Fertility and Sterility Nov 2021
Topics: Congenital Abnormalities; Genitalia; Humans; Kidney; Kidney Diseases; Urogenital Abnormalities
PubMed: 34548168
DOI: 10.1016/j.fertnstert.2021.08.042 -
Development (Cambridge, England) Jul 2020Developmental biologists rely on genetics-based approaches to understand the origins of congenital abnormalities. Recent advancements in genomics have made it easier... (Review)
Review
Developmental biologists rely on genetics-based approaches to understand the origins of congenital abnormalities. Recent advancements in genomics have made it easier than ever to investigate the relationship between genes and disease. However, nonsyndromic birth defects often exhibit non-Mendelian inheritance, incomplete penetrance or variable expressivity. The discordance between genotype and phenotype indicates that extrinsic factors frequently impact the severity of genetic disorders and vice versa. Overlooking gene-environment interactions in birth defect etiology limits our ability to identify and eliminate avoidable risks. We present mouse models of sonic hedgehog signaling and craniofacial malformations to illustrate both the importance of and current challenges in resolving gene-environment interactions in birth defects. We then prescribe approaches for overcoming these challenges, including use of genetically tractable and environmentally responsive systems. Combining emerging technologies with molecular genetics and traditional animal models promises to advance our understanding of birth defect etiology and improve the identification and protection of vulnerable populations.
Topics: Animals; Congenital Abnormalities; Craniofacial Abnormalities; Gene-Environment Interaction; Hedgehog Proteins; Humans; Signal Transduction
PubMed: 32680836
DOI: 10.1242/dev.191064 -
International Journal of Environmental... May 2021Links between heat exposure and congenital anomalies have not been explored in detail despite animal data and other strands of evidence that indicate such links are... (Review)
Review
Links between heat exposure and congenital anomalies have not been explored in detail despite animal data and other strands of evidence that indicate such links are likely. We reviewed articles on heat and congenital anomalies from PubMed and Web of Science, screening 14,880 titles and abstracts in duplicate for articles on environmental heat exposure during pregnancy and congenital anomalies. Thirteen studies were included. Most studies were in North America (8) or the Middle East (3). Methodological diversity was considerable, including in temperature measurement, gestational windows of exposure, and range of defects studied. Associations were detected between heat exposure and congenital cardiac anomalies in three of six studies, with point estimates highest for atrial septal defects. Two studies with null findings used self-reported temperature exposures. Hypospadias, congenital cataracts, renal agenesis/hypoplasia, spina bifida, and craniofacial defects were also linked with heat exposure. Effects generally increased with duration and intensity of heat exposure. However, some neural tube defects, gastroschisis, anopthalmia/microphthalmia and congenital hypothyroidism were less frequent at higher temperatures. While findings are heterogenous, the evidence raises important concerns about heat exposure and birth defects. Some heterogeneity may be explained by biases in reproductive epidemiology. Pooled analyses of heat impacts using registers of congenital anomalies are a high priority.
Topics: Congenital Abnormalities; Female; Heart Defects, Congenital; Hot Temperature; Humans; Middle East; North America; Pregnancy; Temperature
PubMed: 34063033
DOI: 10.3390/ijerph18094910 -
Journal of the American Heart... Jun 2023Background In the palliative pathway of single-ventricle physiology, lymphatic abnormalities on T2-weighted magnetic resonance imaging have been shown after the Glenn...
Background In the palliative pathway of single-ventricle physiology, lymphatic abnormalities on T2-weighted magnetic resonance imaging have been shown after the Glenn operation. It is believed that postsurgical hemodynamic changes contribute to the lymphatic changes.However, little is known about how early these abnormalities occur. Our purpose was to determine if lymphatic abnormalities occur as early as before the Glenn operation. Methods and Results We retrospectively reviewed patients with single-ventricle physiology and a T2-weighted magnetic resonance imaging scan before their Glenn operation (superior cavopulmonary connection) at The Children's Hospital of Philadelphia from 2012 to 2022. Lymphatic perfusion patterns on T2-magnetic resonance imaging were categorized from type 1 (no supraclavicular T2-signal) to type 4 (supraclavicular, mediastinal, lung parenchymal T2-signal). Types 1 and 2 were considered normal variants. Distribution of lymphatic abnormalities were tabulated, as well as secondary outcomes including chylothorax and mortality. Comparison was done using analysis of variance, Kruskal-Wallis test, and Fisher's exact test. Seventy-one children were included: 30 with hypoplastic left heart syndrome and 41 with nonhypoplastic left heart syndrome. Lymphatic abnormalities were present before Glenn operation in 21% (type 3) and 20% (type 4), and normal lymphatic perfusion patterns (type 1-2) were seen in 59% of patients. Chylothorax was present in 17% (only types 3 and 4). Pre-Glenn mortality and mortality at any time was significantly increased when having a type 4 lymphatic abnormality compared with types 1 and 2 (=0.04). Conclusions Lymphatic abnormalities can be found on T2-weighted magnetic resonance imaging in children with single-ventricle physiology before their Glenn operation. Mortality and chylothorax were more prevalent with advancing grade of lymphatic abnormality.
Topics: Child; Humans; Infant; Retrospective Studies; Chylothorax; Treatment Outcome; Heart Defects, Congenital; Fontan Procedure; Univentricular Heart; Lymphatic Abnormalities; Magnetic Resonance Imaging; Heart Ventricles
PubMed: 37318013
DOI: 10.1161/JAHA.123.029376 -
BioMed Research International 2018In the most recent publications on Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, the uterine remnants and ovaries in patients may develop uterine remnant leiomyoma,... (Review)
Review
In the most recent publications on Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, the uterine remnants and ovaries in patients may develop uterine remnant leiomyoma, adenomyosis, or ovarian tumor, and this can lead to problems in differential diagnosis. Here we summarize the diagnosis methods and available interventions for ovarian tumor in MRKH syndrome, with emphasis on the relevant clinical findings and illustrative relevant case. According to the clinical findings and illustrative relevant case, with the help of imaging techniques, ovarian tumors can be detected in the pelvis in patients with MRKH syndrome and evaluated in terms of size. Laparoscopy could further differentiate ovarian tumors into different pathological types. In addition, laparoscopic surgery not only is helpful for the diagnosis of MRKH combined ovarian tumor, but also has a good treatment role for excising ovarian tumor at the same time. Moreover, laparoscopic removals of ovarian tumor can be considered as a safe and reliable treatment for conservative management.
Topics: 46, XX Disorders of Sex Development; Congenital Abnormalities; Female; Humans; Laparoscopy; Mullerian Ducts; Ovarian Neoplasms
PubMed: 29721502
DOI: 10.1155/2018/2369430 -
Prenatal Diagnosis Jan 2018Prenatal genetic diagnosis provides information for pregnancy and perinatal decision-making and management. In several small series, prenatal whole exome sequencing... (Review)
Review
Prenatal genetic diagnosis provides information for pregnancy and perinatal decision-making and management. In several small series, prenatal whole exome sequencing (WES) approaches have identified genetic diagnoses when conventional tests (karyotype and microarray) were not diagnostic. Here, we review published prenatal WES studies and recent conference abstracts. Thirty-one studies were identified, with diagnostic rates in series of five or more fetuses varying between 6.2% and 80%. Differences in inclusion criteria and trio versus singleton approaches to sequencing largely account for the wide range of diagnostic rates. The data suggest that diagnostic yields will be greater in fetuses with multiple anomalies or in cases preselected following genetic review. Beyond its ability to improve diagnostic rates, we explore the potential of WES to improve understanding of prenatal presentations of genetic disorders and lethal fetal syndromes. We discuss prenatal phenotyping limitations, counselling challenges regarding variants of uncertain significance, incidental and secondary findings, and technical problems in WES. We review the practical, ethical, social and economic issues that must be considered before prenatal WES could become part of routine testing. Finally, we reflect upon the potential future of prenatal genetic diagnosis, including a move towards whole genome sequencing and non-invasive whole exome and whole genome testing. © 2017 John Wiley & Sons, Ltd.
Topics: Congenital Abnormalities; Female; Genetic Diseases, Inborn; Humans; Pregnancy; Prenatal Diagnosis; Exome Sequencing
PubMed: 28654730
DOI: 10.1002/pd.5102 -
Journal of Medical Genetics Dec 2020Motor kinesins are a family of evolutionary conserved proteins involved in intracellular trafficking of various cargoes, first described in the context of axonal... (Review)
Review
Motor kinesins are a family of evolutionary conserved proteins involved in intracellular trafficking of various cargoes, first described in the context of axonal transport. They were discovered to have a key importance in cell-cycle dynamics and progression, including chromosomal condensation and alignment, spindle formation and cytokinesis, as well as ciliogenesis and cilia function. Recent evidence suggests that impairment of kinesins is associated with a variety of human diseases consistent with their functions and evolutionary conservation. Through the advent of gene identification using genome-wide sequencing approaches, their role in monogenic disorders now emerges, particularly for birth defects, in isolated as well as multiple congenital anomalies. We can observe recurrent phenotypical themes such as microcephaly, certain brain anomalies, and anomalies of the kidney and urinary tract, as well as syndromic phenotypes reminiscent of ciliopathies. Together with the molecular and functional data, we suggest understanding these 'kinesinopathies' as a recognisable entity with potential value for research approaches and clinical care.
Topics: Brain; Cilia; Ciliopathies; Congenital Abnormalities; Genetic Predisposition to Disease; Humans; Kidney; Kinesins; Microcephaly; Multigene Family; Phenotype; Urinary Tract
PubMed: 32430361
DOI: 10.1136/jmedgenet-2019-106769 -
Neurologia Medico-chirurgica Feb 2017Ethical issues in the field of pediatric neurosurgery, including prenatal diagnosis, palliative care for children with an intractable serious disease, and medical... (Review)
Review
Ethical issues in the field of pediatric neurosurgery, including prenatal diagnosis, palliative care for children with an intractable serious disease, and medical neglect, are discussed. An important role of medicine is to offer every possible treatment to a patient. However, it also is the responsibility of medicine to be conscious of its limitations, and to help parents love and respect a child who suffers from an incurable disease. When dealing with cases of medical neglect and palliative care for an incurable disease, it is critical to diagnose the child's condition accurately and evaluate the outcome. However, to treat or not to treat also depends on the medical resources and social-economic status of the community, the parents' religion and philosophy, the policies of the institutions involved, and the limits of medical science. Moral dilemmas will continue to be addressed as medical progress yields treatments for untreatable diseases in the future.
Topics: Adult; Congenital Abnormalities; Ethics, Medical; Female; Genetic Diseases, Inborn; Humans; Male; Neurosurgery; Palliative Care; Pediatrics; Pregnancy; Prenatal Diagnosis
PubMed: 28025426
DOI: 10.2176/nmc.ra.2016-0122 -
Cells, Tissues, Organs 2018The function of normal and defective candidate genes for human genetic diseases, which are rapidly being identified in large numbers by human geneticists and the... (Review)
Review
The function of normal and defective candidate genes for human genetic diseases, which are rapidly being identified in large numbers by human geneticists and the biomedical community at large, will be best studied in relevant and predictive model organisms that allow high-speed verification, analysis of underlying developmental, cellular and molecular mechanisms, and establishment of disease models to test therapeutic options. We describe and discuss the pros and cons of the frog Xenopus, which has been extensively used to uncover developmental mechanisms in the past, but which is being underutilized as a biomedical model. We argue that Xenopus complements the more commonly used mouse and zebrafish as a time- and cost-efficient animal model to study human disease alleles and mechanisms.
Topics: Alleles; Animals; Ciliary Motility Disorders; Ciliopathies; Congenital Abnormalities; Disease Models, Animal; Genetic Diseases, Inborn; Heart Defects, Congenital; Humans; Mutation; Xenopus laevis
PubMed: 30092565
DOI: 10.1159/000490898 -
International Journal of Molecular... Oct 2021Congenital anomalies of the female reproductive tract that present with primary amenorrhea involve Müllerian aplasia, also known as Mayer-Rokitansky-Küster-Hauser... (Review)
Review
Congenital anomalies of the female reproductive tract that present with primary amenorrhea involve Müllerian aplasia, also known as Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), and cervical and vaginal anomalies that completely obstruct the reproductive tract. Karyotype abnormalities do not exclude the diagnosis of MRKHS. Familial cases of Müllerian anomalies and associated malformations of the urinary and skeletal systems strongly suggest a complex genetic etiology, but so far, the molecular mechanism in the vast majority of cases remains unknown. Primary amenorrhea may also be the first presentation of complete androgen insensitivity syndrome, steroid 5α-reductase type 2 deficiency, 17β-hydroxysteroid dehydrogenase type 3 deficiency, and Leydig cells hypoplasia type 1; therefore, these disorders should be considered in the differential diagnosis of the congenital absence of the uterus and vagina. The molecular diagnosis in the majority of these cases can be established.
Topics: 17-Hydroxysteroid Dehydrogenases; 46, XX Disorders of Sex Development; Amenorrhea; Androgen-Insensitivity Syndrome; Cervix Uteri; Cholestenone 5 alpha-Reductase; Congenital Abnormalities; Disorder of Sex Development, 46,XY; Female; Humans; Male; Mullerian Ducts; Testis; Vagina
PubMed: 34768925
DOI: 10.3390/ijms222111495