Teratogenic Agents Research Articles

Congenital diaphragmatic hernia: a case series in tertiary care centre

Congenital diaphragmatic hernia (CDH) is the presence of a defect in the diaphragm that allows the herniation of the abdominal viscera into the thorax. The mortality is the result of persistent pulmonary hypertension and respiratory insufficiency due to abnormal pulmonary vessels and hypoplastic lungs. The incidence of congenital diaphragmatic hernia is 1 in 2500 births. The etiology of congenital diaphragmatic hernia remains unclear. It is thought to be multifactorial with genetic, environmental, and/or nutritional factors playing a role. CDH can be an isolated anomaly or associated with anomalies in other organ systems. The most frequent aneuploidies associated with CDH include trisomy 18, trisomy 13, trisomy 21, and less frequently Turner syndrome (45, X). Exposure to teratogenic agents like mycophenolate mofetil, allopurinol, and lithium during pregnancy is reported to be associated with CDH. Recently, studies indicate disturbances in the retinoid-signaling pathway as a potential cause of CDH. This case series aims to pull importance of a viable protocol for antenatal evaluation of CDH, and meanwhile to underline the importance of a good interdisciplinary antenatal evaluation of these cases for the fetal outcome.

Mermaid syndrome: Rare genetic anomaly.

Mermaid syndrome (Sirenomelia) is a rare fatal congenital anomaly. The prevalence is reported to be 1 in 100,000 births. The baby appears to have a fish-like tail and joined legs featuring a mermaid at the time of birth or during antenatal screening. Most of these patients die shortly after birth, denoting rare survival rate. Gastrointestinal and genitourinary obstruction with single umbilical artery are the clinical symptoms. Two important hypotheses support the Sirenomelia disorder: the artery steal hypothesis, called the vitelline artery, and the blastogenesis defect hypothesis. There is no known reason for MS, but certain risk factors need to be identified, which include mother aged more than 40 years or less than 20 years at the time of giving birth, cousin marriage, exposure to teratogenic agents, and family history. A case of this rare congenital disorder was seen in Civil Hospital Faisalabad, Pakistan, which was referred from Duniyapur, District Lodhran, Pakistan. The neonate presented with fused lower limbs, congenital heart disease, and high-grade fever. The mother had a history of gestational diabetes mellitus and hypertension. The baby had fused legs, unidentified internal and external genital system, thumbs anomaly, bile in vomit, and despite life-saving efforts, the patient expired after five days of birth. There is lack of information regarding symptoms and a lack of prenatal screening for MS. Hence, there is a need to create awareness among health care professionals to identify the disease on screening for early diagnosis.

A rare clinical image of anencephaly

Anencephaly is a medical condition where the fetus has no calvarium with no or lack of the brain tissue. This belongs to neural tube defects where the neural tube fails to close. In rural areas, the lack of prenatal care and prenatal follow-up of the mother mostly leads to this malformation in the fetus. A pregnant mother of 36 weeks of gestation with no history of diabetes mellitus, epilepsy, or known exposure to teratogenic agents was taken to the hospital with labor pain. The case was taken to the C-section due to fetal distress. The baby didn’t cry immediately after the birth, resuscitation was performed immediately. There was no calvarium, no scalp, external presence of hemorrhagic tissue, and lack of cerebral hemisphere was noted. The left leg of the fetus was not developed completely. The father and family members were informed and counseled about the condition. The economic condition of the family couldn’t afford the higher medical management. The baby passed after 5 hrs of life. Counseling of the mother was done and the importance of prenatal care during pregnancy was informed to the family. Anencephaly does not support life, prevention is the only way to avoid this condition. With proper prenatal care and counseling, this can be achieved. The most important part of the treatment for the mother is counseling to overcome or avoid postpartum depression and its complications.

Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model

BackgroundUntil now, the treatment of patients with autism spectrum disorder (ASD) remain a difficult problem. The insula is involved in empathy and sensorimotor integration, which are often impaired in individuals with ASD. Deep brain stimulation, modulating neuronal activity in specific brain circuits, has recently been considered as a promising intervention for neuropsychiatric disorders. Valproic acid (VPA) is a potential teratogenic agent, and prenatal exposure can cause autism-like symptoms including repetitive behaviors and defective sociability. Herein, we investigated the effects of continuous high-frequency deep brain stimulation in the anterior insula of rats exposed to VPA and explored cognitive functions, behavior, and molecular proteins connected to autism spectrum disorder.MethodsVPA-exposed offspring were bilaterally implanted with electrodes in the anterior insula (Day 0) with a recovery period of 1 week. (Day 0–7). High-frequency deep brain stimulation was applied from days 11 to 29. Three behavioral tests, including three-chamber social interaction test, were performed on days 7, 13, 18, 25 and 36, and several rats were used for analysis of immediate early genes and proteomic after deep brain stimulation intervention. Meanwhile, animals were subjected to a 20 day spatial learning and cognitive rigidity test using IntelliCage on day 11.ResultsDeep brain stimulation improved the sociability and social novelty preference at day 18 prior to those at day 13, and the improvement has reached the upper limit compared to day 25. As for repetitive/stereotypic-like behavior, self- grooming time were reduced at day 18 and reached the upper limit, and the numbers of burried marbles were reduced at day 13 prior to those at day 18 and day 25. The improvements of sociability and social novelty preference were persistent after the stimulation had ceased. Spatial learning ability and cognitive rigidity were unaffected. We identified 35 proteins in the anterior insula, some of which were intimately linked to autism, and their expression levels were reversed upon administration of deep brain stimulation.ConclusionsAutism-like behavior was ameliorated and autism-related proteins were reversed in the insula by deep brain stimulation intervention, these findings reveal that the insula may be a potential target for DBS in the treatment of autism, which provide a theoretical basis for its clinical application., although future studies are still warranted.

Effects of Common Teratogens on Prenatal Development: Alcohol, Smoking, and Drugs

Teratogens are responsible for a large number of congenital abnormalities. The repercussions of ignorance to the agents a pregnant person could possibly be exposed to can result in irreversible malformation in a fetus. This paper uses studies done by the National Institutes of Health (NIH) and Centers for Disease Control and Prevention (CDC) to explore three major teratogenic agents--alcohol, smoking, and drugs--and the effects they can have on a fetus on the molecular level, with a focus on the specific components that cause the defects and the possible abnormalities that the fetus is at risk of.

Cyclophosphamide Induces Lipid and Metabolite Perturbation in Amniotic Fluid during Rat Embryonic Development.

Cyclophosphamide (CP) has been proven to be an embryo-fetal toxic. However, the mechanism responsible for the toxicity of the teratogenic agent has not been fully explored. This study aimed to examine the teratogenicity of CP when administered in the sensitive period of pregnant rats. The effect of CP on the lipid and metabolic profiles of amniotic fluid was evaluated using a UHPLC-Q-Exactive Orbitrap MS-based method. Metabolome analysis was performed using the MS-DIAL software with LipidBlast and NIST. Initially, we identified 636 and 154 lipid compounds in the positive and negative ion modes and 118 metabolites for differential analysis. Mainly 4 types of oxidized lipids in the amniotic fluid were found to accumulate most significantly after CP treatment, including very-long-chain unsaturated fatty acids (VLCUFAs), polyunsaturated fatty acid (PUFA)-containing triglycerides (TGs), oxidized phosphatidylcholine (PC), and sphingomyelin (SM). Tryptophan and some long-chain saturated fatty acids were lowered pronouncedly after CP treatment. These findings suggest that CP may exert teratogenic toxicity on pregnant rats through maternal and fetal oxidative stress. The UHPLC-Q-Exactive Orbitrap MS-based lipidomics approach is worthy of wider application for evaluating the potential toxicity of other agents (toxicants) during embryonic development.

TCDD induces cleft palate through exosomes derived from mesenchymal cells.

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a ubiquitous environmental toxicant and a notable teratogenic agent for cleft palate (CP), a common congenital structural malformation that can result from abnormalities during palatal shelf connection and/or fusion. The development of the palate requires precise coordination between mesenchymal and epithelial cells. Exosomes are vesicles secreted by cells and participate in organ development by transferring various bioactive molecules between cells and regulating cell proliferation, migration, apoptosis, and epithelial-mesenchymal transition (EMT); these vesicles represent a new method of intercellular communication. To explore how TCDD could influence palatal cell behaviors and communication, we treated mesenchymal cells with TCDD, collected the exosomes secreted by the cells, assessed the 2 types of palatal cells, and then observed the effects of TCDD-induced exosomes. We found that the effects of TCDD-induced exosomes were equal to those of TCDD. Thus, TCDD might change the genetic materials of palatal cells and exosomes to cause dysregulated gene expression from parental cells, affect cellular information communicators, and induce abnormal cellular behaviors that could lead to CP.

Carbendazim toxicity in different cell lines and mammalian tissues.

The extensive production and use of harmful pesticides in agriculture to improve crop yield has raised concerns about their potential threat to living components of the environment. Pesticides cause serious environmental and health problems both to humans and animals. Carbendazim (CBZ) is a broad spectrum fungicide that is used to control or effectively kill pathogenic microorganisms. CBZ is a significant contaminant found in food, soil and water. It exerts immediate and delayed harmful effects on humans, invertebrates, aquatic animals and soil microbes when used extensively and repeatedly. CBZ is a teratogenic, mutagenic and aneugenic agent that imparts its toxicity by enhancing generation of reactive oxygen species generation. It elevates the oxidation of thiols, proteins and lipids and decreases the activities of antioxidant enzymes. CBZ is cytotoxic causing hematological abnormalities, mitotic spindle deformity, inhibits mitosis and alters cell cycle events which lead to apoptosis. CBZ is known to cause endocrine-disruption, embryo toxicity, infertility, hepatic dysfunction and has been reported to be one of the leading causes of neurodegenerative disorders. CBZ is dangerous to human health, the most common side effects upon chronic exposure are thyroid gland dysfunction and oxidative hepato-nephrotoxicity. In mammals, CBZ has been shown to disrupt the antioxidant defense system. In this review, CBZ-induced toxicity in different cells, tissues and organisms, under in vitro and in vivo conditions, has been systematically discussed.

A CASES OF LIMB BODY WALL SYNDROME (LBW): REPORT AND LITERATUREREVIEW

Limb body wall syndrome (LBW) is one of the rarest malformation complexes. It is also known by other names as « Abnormal stem of the body » « Congenital absence of the umbilical cord » and « cyllosome and Pleurosomus » [1]. This complex is a heterogeneous disease characterized by multiple severe congenital abnormalities of the fetus with exencephalon/thoraco-encephalo and/or abdominoschisis (anterior parietal malformations) and malformations of the limbs, with or without facial slits. The diagnosis remains difficult to establish in view of the clinical polymorphism the prenatal ultrasound can detect this abnormality during the first trimester. The exact etiology of this condition is still uncertain, the theory of amniotic bands of Tropin and the vascular theory (early vascular accident) of Van Allen have not succeeded in explaining all the abnormalities observed in the LBWC [2]. Karyotype study are normal and there has been no evidence of correlation with sex, age of parents or teratogenic agents. Prognosis is fatal death occurring in antenatal or early neonatal period. We are describing two cases of Limb body wall syndrome (LBW).

ZIKV Teratogenesis: Clinical Findings in Humans, Mechanisms and Experimental Models

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) from the Flaviviridae family, first isolated from the Rhesus monkey in 1947 in Uganda. ZIKV is transmitted by mosquito bites, but vertical and sexual transmissions have also been reported. ZIKV infection during pregnancy causes malformation in the developing fetus, especially central nervous system (CNS) damages, with a noticed microcephaly, making ZIKV be recognized as a teratogenic agent and the responsible for congenital Zika syndrome (CZS). However, it is still a short time since CZS was first reported. Consequently, ZIKV pathogenesis is not entirely elucidated, especially considering that affected children are still under neurodevelopment. Here, we will explore the current knowledge about ZIKV teratogenesis focusing on neurological clinical findings in humans, mechanisms, and experimental models used to understand ZIKV pathophysiology.

Factores de riesgo genético y diagnóstico prenatal

Objective: To identify genetic risk factors and frequency and to describe congenital defects of the fetus. Methods: The research was conducted at the Genetic Research Institute of the Faculty of Medicine. University of Zulia. Maracaibo. We studied patients who attend to the prenatal genetic clinic. According to the Genetic risk factors Identified, it indicated different prenatal diagnostic procedures: fetal echography, fetal echocardiography, triple maternal serum marker, amniocentesis for fetal karyotype and molecular analysis. Results: We included 568 patients. 79.05% of the total showed only one genetic risk factor and the 20.95% two or more. The advanced maternal age was the most frequent genetic risk factor found (40.85%), followed by first-degree family history with a congenital defect (35.21%), abnormal fetal echography (13.73%), exposure to teratogenic agents (10.39%), history of recurrent abortion (7.04%), history of fetal death (4.22%), consanguinity (1.93%), and history of neonatal death (1.76%). They were diagnosed 101 fetuses with congenital defects, one balanced translocation, two fetal deaths and 26 spontaneous abortions. Conclusion: The genetic risk factors identification, served as a starting point to indicate prenatal diagnostic procedures allowed a health evaluation of the fetus and adequate genetic counseling. Key words: Prenatal diagnosis, Risk factors, Genetic counseling.

Онтологія варіантів будови та вад розвитку черепа. Частина I

Annually severe congenital abnormalities occur in 1 of 33 newborns or about 125.000 live births in the United States and are the leading cause of infant mortality. Craniofacial anomalies account for about one-third of all abnormalities. The prevalence of human congenital malformations is an important characteristic of public health. According to the World Health Organization, the birth rate of children with cleft lip and palate is on average 1:750 newborns, which is 20-30% of all human malformations and 86% of maxillofacial malformations. They contribute significantly to infant morbidity and disability as well as millions of dollars in health care costs each year. Development of the human skull begins about 23-26 days after fertilization, when a multipotent population of cranial neural crest cells migrates from the dorsal part of the neuraxis to the embryonic head region, giving rise to the frontal bone and interparietal part of the occipital bone, while the rest of the cranial arch comes mainly from the mesoderm. A malformation is a deviation from the normal development of an organ or tissue. Among the causes are chromosomal abnormalities, single gene defects, teratogenic or multi-factor agents, that is, a combination of genetic and external factors; the smallest number of cases are idiopathic. Exogenous causes of human congenital abnormalities include: physical (mechanical, thermal, radiation); chemical (hypoxia, malnutrition, hormonal discordance, teratogenic poisons); biological (viruses, bacteria and their toxins, protozoa); mental factors. Endogenous causes are heredity (changes in hereditary structures, mutations); biological inadequacy of germ cells (endocrine disorders, “over-ripening” of germ cells); parents’ age. Congenital craniofacial abnormalities are caused by improper growth and/or development of the brain and facial parts of the skull and soft tissue. Craniofacial abnormalities affecting the skull include macrocephaly, microcephaly and unilateral deformities. Sometimes cranial sutures fuse too early and craniosynostosis occurs, which is accompanied by various cranial deformities. This leads to abnormal cranial development, which can cause dysmorphia, and in the most severe cases catastrophically affect brain development. Conclusion. Based on the analysis of the literature sources, an attempt has been made to summarize the existing information and classifications of congenital cranial abnormalities, as well as the interpretation of various anomalies of the brain and facial skull in alphabetic order. The most common stigmas and malformations of the skull bones are briefly characterized

Sirenomelia: two case\xa0reports

BackgroundSirenomelia, also called mermaid syndrome, is a rare lethal multi-system congenital deformity with an incidence of one in 60,000–70,000 pregnancies. Sirenomelia is mainly characterized by the fusion of lower limbs and is widely associated with severe urogenital and gastrointestinal malformations. The presence of a single umbilical artery derived from the vitelline artery is the main anatomical feature distinguishing sirenomelia from caudal regression syndrome. First-trimester diagnosis of this disorder and induced abortion may be the safest medical option. In this report, two cases of sirenomelia that occurred in an white family will be discussed.Case presentationWe report two white cases of sirenomelia occurring in a 31-year-old multigravid pregnant woman. In the first pregnancy (18 weeks of gestation) abortion was performed, but in the third pregnancy (32 weeks) the stillborn baby was delivered by spontaneous vaginal birth. In the second and fourth pregnancies, however, she gave birth to normal babies. Three-dimensional ultrasound imaging showed fusion of the lower limbs. Neither she nor any member of her family had a history of diabetes. In terms of other risk factors, she had no history of exposure to teratogenic agents during her pregnancy. Also, her marriage was non-consanguineous.ConclusionThis report suggests the existence of a genetic background in this mother with a Mendelian inheritance pattern of 50% second-generation incidence in her offspring.

Agentes teratogênicos e desenvolvimento fetal: Uma revisão narrativa

Mundialmente, segundo o Global Report on Birth Defects, cerca de 7,9 milhões de bebês – 6% do total de nascimentos – possuem ao nascimento alguma malformação congênita de origem genética ou parcialmente genética, enquanto outras centenas de milhares nascem com malformações congênitas desenvolvidas por causas evitáveis. A prevalência das causas de malformações não-genéticas é estipulada em torno de 5 a 10%, principalmente, associadas à exposição materna a agentes teratogênicos, como medicamentos, álcool, tabaco, drogas ilícitas, micro-organismos, radiação, poluição ambiental, entre outros. Desta forma objetivou-se nesse estudo identificar a influência de alguns dos principais agentes teratogênicos químicos e biológicos nas malformações congênitas, através de uma revisão narrativa de literatura.

Prevention and Early Detection of Congenital Heart Defects. Where do we stand.

Introduction: Since the origin of Medicine in 4th BC. Century research has taught us that learning and practicing preventive medicine is properly the best method to prevent disease from happening in the first place. Preventive health care must be planned and executed ahead of time, even when illness/ disease, is absent, especially for those that are common and fаtal. Among neonates and infants, congenital heart disease (CHD) is responsible for the largest proportion of mortality caused by birth defects. Actual numbers of patients and mortality resulting from CHD reportedly is increasing. In the developed world the treatment of CHD has escalating costs for health care systems and private covered patients, while in low-income countries it is not always available. Prevention is urgently needed to tackle the increasing needs.
 Aim: To present the current practice in preventing/early detecting CHD and justify why pulse oximetry is the best available, early detecting postnatal screening test we currently have.
 Methods: The existing in use preventing/early detecting methods for avoiding or early diagnosing CHD are: 1. Eliminate the maternal risk factors by obtaining a good level of health and medical surveillance during pregnancy. 2. Avoiding teratogenic agents, 3. Detecting risk factors from Family History, 4. Delivering a balanced Nutrition during Pregnancy 5. Obtaining at least an experienced 4-chamber view and outflow tracts imaging during the 20-weeks anomaly scan. 6. Fetal Echocardiography when indicated 7. Postnatal evaluation by experienced Pediatricians. 8. Pulse Oximetry, screening test after 72 hours post-delivery in term babies. 9. Hyperoxia test when indicated.
 Conclusion: Although CHD’s are the most common, high morbidity and mortality, congenital malformations, we still lack a single, easy to apply, non-invasive and low-cost screening test, for early detection. The current preventive methods must be combined to counterbalance the CHD prevalence. Meanwhile, they are costly and partially accessible. The most advantageous method for minimizing CHD deaths worldwide seems to be currently, pulse oximetry combined with clinical assessment.
 Original publication: Petropoulos AC. Prevention and Early Detection of Congenital Heart Defects. Where do we Stand. J Cardiol 2018, 2(1): 000111.

A case of phocomalia in young primi gravida

Introduction: Phocomelia is a type of meromelia, in which there is partial agenesis of limb buds. Tetraphocomelia is a severe combination of limb defects in which total or partial agenesis of upper and lower limbs is seen, leading to the proximity of limbs to the trunk of the fetus resembling the flipper of a seal “an aquatic animal”.1 Keyword: Tetraphocomeia, Thalidornide syndrome, phocomelia, Limbs defects, Teratogenic agents, Hydroamniosis, Genetic inheritance.

Maternal infections with an increased risk of transmission to the foetus; a literature review

Screening testing for infectious diseases with vertical transmission, from mother to foetus, decreases the prevalence of foetal malformations. The most common infections with teratogenic potential are found in the TORCH test (Toxoplasma, Other infections, Rubella, Cytomegalovirus, Herpes simplex virus). Early identification of these pathogens results in better neonatal outcomes. Most foetuses with congenital toxoplasmosis are asymptomatic or have no apparent birth defect, while the primary infection of pregnancy with varicella-zoster virus (VZV) can lead to congenital foetal abnormalities with devastating consequences. Treponema pallidum can easily infect the placenta, with transplacental transmission to the foetus that can occur from about 9-10 weeks of gestation. Also, hepatitis B and C are the most common causes of chronic viral hepatitis in children and adults. In the case of HIV-positive pregnant women, the early association of ART, together with the choice of birth by scheduled caesarean section and the complete lack of breastfeeding determine expected neonatal results, the risk of vertical transmission decreasing up to 1-2%. Primary rubella infection during pregnancy can significantly affect foetal development, as does Herpes simplex virus (HSV) infection, but if it occurs as close as possible to birth, the disease may be self-limiting with mild forms. No teratogenic agent should be described qualitatively, as a teratogenic exposure includes not only the agent but also the dose and time of pregnancy when the exposure will occur. Screening tests are recommended to be performed both preconceptionally and during pregnancy.

Descriptive analyse of a case control study in Portugal: identify to prevent

Abstract Background Prenatal exposure to environmental risk factors are one of the known causes of congenital anomalies (CA). In 2015, a cluster of anorectal anomalies, a rare malformation, in Setúbal district raised interest in researchers. The aim of study was to assess the impact of prenatal exposure of the mothers on the occurrence of CA in the offspring. Methods A Case-control study (1:2) was implemented between 2016-2019. Newborns with CA (cases) and newborns without CA (controls) are identified and recruited. Parents were personally interviewed by a health professional using a standardized questionnaire. A descriptive analyses was performed and cases and controls were described based on maternal residence during pregnancy. Chi-square test was used to compare cases and controls. Results 97 cases and 194 controls were identified. There was a male predominance in the case group (60 vs. 34) and no difference in gestational age between case and control groups. The mean birth weight was similar (3115g in cases vs. 3221g in controls). There was no difference related to mean mother's age nor the presence of maternal chronic disease. Smoking had more expression in the case group (21,2% vs. 16,3%). Moita (37,8%) is the municipality with higher frequency of cases. Musculoskeletal anomalies were the most frequent (35.4%), followed by genital (22.2%) and other anomalies (11%). During the study period, five cases with anorectal anomalies were reported, 4 of them born at 2016 and in 3 the mothers residence place was Moita. Conclusions In this study, the high proportion of cases from Moita suggests a possible environmental exposure to a teratogenic agent. Also smoking during pregnancy could be a high risk to anorectal anomalies, as suggested in other studies. More investment in public health measures could protect population from harmful environments. Key messages Pprenatal exposure to environemental risk factors increase the risk of congenital anomalies. Mothers residence and place of work could be a risk factor to pregnancy.

Prenatal Supplementation with Curcuma longa Ameliorates Oxidative Stress, Improves Behaviour and Hippocampal Alterations in Valproic Acid-Induced Autism in Sprague-Dawley Rat

There is growing global number of persons affected with autism, and teratogenic influences arising from several epigenetic factors have been implicated. This study aimed to determine the effect of prenatal supplementation of extract of Curcuma longa on valproic acid-induced model of autism in Sprague-Dawley rats. Thirty pregnant Sprague-Dawley rats divided into five groups (n=6) were used. Valproic acid (500 mg/kg body weight) induced autism on gestation day 12.5. The groups were designated as control, valproic acid, and valproic acid with 5, 10 and 20 mg/kg body weights Curcuma longa respectively, (Curcuma longa was administered from day 1-21 of gestation). On postnatal day 21, five male pups were randomly selected from each group, and neurobehavioral tests were performed until postnatal day 28. The pups were sacrificed on postnatal day 28, and the hippocampus was dissected for histology and biochemical assays. Treated groups showed improvement in anxiety and social behaviour. The histological sections showed fewer atrophied cells, reduced degree of chromatolysis with better delineation of the cells within the pyramidal layer compared with valproic acid group. Dopamine, lL-6 and TGF β1 levels were not significantly different from control. Malondialdehyde and glutathione values of the treated groups were significantly different from valproic acid groups. Superoxide dismutase and catalase showed no significant difference when treated groups were compared to valproic acid group except the medium dose for catalase. This study shows that prenatal supplementation with Curcuma longa is a potential ameliorative agent against teratogenic epigenetic agents that may lead to autism.

Ion Channel Contributions to Morphological Development: Insights From the Role of Kir2.1 in Bone Development.

The role of ion channels in neurons and muscles has been well characterized. However, recent work has demonstrated both the presence and necessity of ion channels in diverse cell types for morphological development. For example, mutations that disrupt ion channels give rise to abnormal structural development in species of flies, frogs, fish, mice, and humans. Furthermore, medications and recreational drugs that target ion channels are associated with higher incidence of birth defects in humans. In this review we establish the effects of several teratogens on development including epilepsy treatment drugs (topiramate, valproate, ethosuximide, phenobarbital, phenytoin, and carbamazepine), nicotine, heat, and cannabinoids. We then propose potential links between these teratogenic agents and ion channels with mechanistic insights from model organisms. Finally, we talk about the role of a particular ion channel, Kir2.1, in the formation and development of bone as an example of how ion channels can be used to uncover important processes in morphogenesis. Because ion channels are common targets of many currently used medications, understanding how ion channels impact morphological development will be important for prevention of birth defects. It is becoming increasingly clear that ion channels have functional roles outside of tissues that have been classically considered excitable.