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Current Topics in Developmental Biology 2023Birth defects are relatively common congenital outcomes that significantly impact affected individuals, their families, and communities. Effective development and... (Review)
Review
Birth defects are relatively common congenital outcomes that significantly impact affected individuals, their families, and communities. Effective development and deployment of prevention and therapeutic strategies for these conditions requires sufficient understanding of etiology, including underlying genetic and environmental causes. Tremendous progress has been made in defining the genetic basis of familial and syndromic forms of birth defects. However, the majority of birth defect cases are considered nonsyndromic and thought to result from multifactorial gene-environment interactions. While substantial advances have been made in elucidating the genetic landscape of these etiologically complex conditions, significant biological and technical constraints have stymied progress toward a refined knowledge of environmental risk factors. Defining specific gene-environment interactions in birth defect etiology is even more challenging. However, progress has been made, including demonstration of critical proofs of concept and development of new conceptual and technical approaches for resolving complex gene-environment interactions. In this review, we discuss current views of multifactorial birth defect etiology, comparing them with other diseases that also involve gene-environment interactions, including primary immunodeficiency and cancer. We describe how various model systems have illuminated mechanisms of multifactorial etiology and these models' individual strengths and weaknesses. Finally, suggestions for areas of future emphasis are proposed.
Topics: Humans; Gene-Environment Interaction; Congenital Abnormalities
PubMed: 36707208
DOI: 10.1016/bs.ctdb.2022.10.001 -
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 -
Clinical Obstetrics and Gynecology Mar 2022Uterine transplantation is an emerging treatment for patients with uterine factor infertility (UFI). In order to determine patient candidacy for transplant, it is...
Uterine transplantation is an emerging treatment for patients with uterine factor infertility (UFI). In order to determine patient candidacy for transplant, it is imperative to understand how to identify, counsel and treat uterine transplant recipients. In this article, we focus on patient populations with UFI, whether congenital or acquired, including Mayer-Rokitansky-Kuster-Hauser, complete androgen insensitivity syndrome, hysterectomy, and other causes of nonabsolute UFI. Complete preoperative screening of recipients should be required to assess the candidacy of each individual prior to undergoing this extensive treatment option.
Topics: 46, XX Disorders of Sex Development; Congenital Abnormalities; Female; Humans; Infertility; Male; Mullerian Ducts; Uterus
PubMed: 35045021
DOI: 10.1097/GRF.0000000000000672 -
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 -
Acta Obstetricia Et Gynecologica... May 2022Several studies have reported on the maternal age-associated risks of congenital anomalies. However, there is a paucity of studies with comprehensive review of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Several studies have reported on the maternal age-associated risks of congenital anomalies. However, there is a paucity of studies with comprehensive review of anomalies. We aimed to quantify the risk of birth defects in children born to middle-aged mothers compared with that in children born to young or older mothers.
MATERIAL AND METHODS
We classified maternal ages into three groups: young (<20 years old), middle (20-34 years old) and older age (≥35 years old). Observational studies that met our age criteria were eligible for inclusion. The articles searched using the Embase and MEDLINE databases were those published from 1989 to January 21, 2021. The Newcastle-Ottawa scale was used to assess the risk of bias. If heterogeneity exceeded 50%, the random effect method was used; otherwise, the fixed-effect method was used. Prospero registration number: CRD42021235229.
RESULTS
We included 15 cohort, 14 case-control and 36 cross-sectional studies. The pooled unadjusted odds ratio (95% CI) of any congenital anomaly was 1.64 (1.40-1.92) and 1.05 (0.95-1.15) in the older and young age groups, respectively (very low quality of evidence). The pooled unadjusted odds ratio of chromosomal anomaly was 5.64 (5.13-6.20) and 0.69 (0.54-0.88) in the older and young age groups, respectively. The pooled unadjusted odds ratio of non-chromosomal anomaly was 1.09 (1.01-1.17) and 1.10 (1.01-1.21) in the older and young age groups, respectively (very low quality of evidence). The incidence of abdominal wall defects was increased in children of women in the young maternal age group.
CONCLUSIONS
We identified that very low quality evidence suggests that women in the older maternal age group had increased odds of having children with congenital anomalies compared with those in the 20-34 year age group. There was no increase in odds of children with congenital anomalies in women of <20 year age group except for abdominal defects compared with those in the 20-34 year age group. The results stem from very low quality evidence with no adjustment of confounders.
Topics: Adult; Case-Control Studies; Child; Cohort Studies; Congenital Abnormalities; Cross-Sectional Studies; Female; Humans; Maternal Age; Middle Aged; Parturition; Pregnancy; Young Adult
PubMed: 35288928
DOI: 10.1111/aogs.14339 -
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 -
Paediatric Respiratory Reviews Feb 2020A laryngotracheoesophageal cleft (LC) is a rare congenital anomaly of the upper aerodigestive tract resulting from the absence of fusion of the posterior cricoid lamina,... (Review)
Review
A laryngotracheoesophageal cleft (LC) is a rare congenital anomaly of the upper aerodigestive tract resulting from the absence of fusion of the posterior cricoid lamina, which affects an abnormal communication between the larynx, trachea and esophagus. The genetic etiology of LC remains elusive. The involvement of genetic factors in the development of LC is suggested by reports of familial occurrence, and the increased prevalence of component features among first-degree relatives of affected individuals and murine knockout models. No consistent pattern of inheritance has been found in nonsyndromic patients, except for cases associated with described syndromes. Once the syndrome related to the laryngeal cleft is considered, an active search for the cleft must be initiated. The genetic evaluation of patients with LCs should be guided by the type and location of the malformation, specific medical history and a detailed physical examination. The application of genetic approaches, such as microarrays and exome sequencing might lead to elucidating the etiology of LCs.
Topics: Anal Canal; Arthrogryposis; CHARGE Syndrome; Congenital Abnormalities; Craniofacial Abnormalities; DiGeorge Syndrome; Ear; Ear Diseases; Esophagus; Heart Defects, Congenital; Humans; Hypertelorism; Hypopituitarism; Hypospadias; Intellectual Disability; Kidney; Larynx; Limb Deformities, Congenital; Pallister-Hall Syndrome; Spine; Trachea
PubMed: 31734186
DOI: 10.1016/j.prrv.2019.09.004 -
The Medical Journal of Australia Aug 2021
Topics: Aged; Congenital Abnormalities; Dyspnea; Female; Follow-Up Studies; Hernia, Diaphragmatic; Humans; Kidney; Thoracic Diseases; Tomography, X-Ray Computed
PubMed: 34244994
DOI: 10.5694/mja2.51164 -
Urology May 2021Structural anomalies of the female reproductive tract, known as Mullerian anomalies, can occur in isolation or in association with anomalies of other organ systems. Due... (Review)
Review
Structural anomalies of the female reproductive tract, known as Mullerian anomalies, can occur in isolation or in association with anomalies of other organ systems. Due to shared embryology, the most common association in up to 40% of patients is with renal, ureteral, and bladder anomalies. Affected girls can have a wide range of genitourinary symptoms with urologists playing an integral role in their diagnosis and treatment. To facilitate the recognition and management of these conditions, we provide a review of Mullerian anomalies including the embryology, classifications, syndromes, evaluation, and treatments with attention to their urologic applicability.
Topics: 46, XX Disorders of Sex Development; Anorectal Malformations; Anus, Imperforate; Congenital Abnormalities; Female; Genitalia, Female; Hernia, Umbilical; Humans; Mullerian Ducts; Scoliosis; Urinary Tract; Urogenital Abnormalities
PubMed: 32387292
DOI: 10.1016/j.urology.2020.04.088 -
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