Disease relevance of Abnormalities

• Cleft lip, with or without cleft palate (CL/P), is one of the most common birth defects, occurring in 0.4 to 2.0 per 1,000 infants born alive [1].
• Partial absence of the sacrum is a rare congenital defect which also occurs as an autosomal dominant trait; association with anterior meningocoele, presacral teratoma and anorectal abnormalities constitutes the Currarino triad (MIM 176450) [2].
• Haploinsufficiency of Tbx1 is likely a major determinant of cardiac and craniofacial birth defects associated with DiGeorge syndrome [3].
• Fanconi anemia (FA) consists of a group of at least five autosomal recessive disorders that share both clinical (e.g., birth defects and hematopoietic failure) and cellular (e.g., sensitivity to cross-linking agents and predisposition to apoptosis) features with each other [4].
• The involvement of vitamin K metabolism and function in two well characterized birth defects, warfarin embryopathy and vitamin K epoxide reductase deficiency, suggests that developmental signals from K-dependent pathways may be required for normal embryogenesis [5].

Psychiatry related information on Abnormalities

• Based on these observations, we propose that inhibition of histone deacetylase provides a mechanism for valproic acid-induced birth defects and could also explain the efficacy of valproic acid in the treatment of bipolar disorder [6].
• Small ring (X) chromosomes lacking the XIST gene at Xq13.2 have been associated with a severe phenotype that includes mental retardation, facial dysmorphism and congenital abnormalities [7].
• We found no indication of increased birth defect severity, delays in development, or hyperkinetic syndrome with paternal dioxin [8].
• Alcohol abuse is associated with platelet dysfunction, chronic hypertension, and alcohol-related birth defects [9].
• Analysis of isoniazid and other oral antituberculosis drug use during the second and third months of gestation, i.e., in the critical period for most major congenital abnormalities, in case-control pairs did not indicate a teratogenic effect of these drugs in any group with congenital abnormality [10].

High impact information on Abnormalities

• Folic acid antagonists during pregnancy and risk of birth defects [11].
• These results identify a temporal window of susceptibility to retinoids that is critical for mammalian inner ear specification, and provide the first evidence that a subteratogenic dose of vitamin A derivative can be effective in rescuing a congenital defect in the mammalian embryo [12].
• Absence of birth defects in offspring of women treated with dactinomycin [13].
• Agent Orange and birth defects (continued) [14].
• These genetic data in mouse, fish and human indicate that VEGF is a modifier of cardiovascular birth defects in the del22q11 syndrome [15].

Chemical compound and disease context of Abnormalities

• Vitamin A and birth defects. Continuing caution is needed [16].
• The sedative drug thalidomide ([+]-alpha-phthalimidoglutarimide), once abandoned for causing birth defects in humans, has found new therapeutic license in leprosy and other diseases, with renewed teratological consequences [17].
• Veratrum alkaloids and distal inhibitors of cholesterol biosynthesis have been studied for more than 30 years as potent teratogens capable of inducing cyclopia and other birth defects [18].
• The review then summarizes our current understanding of the molecular mechanisms involved in selected birth defects following exposure to pharmacological compounds, including thalidomide, retinoids, and valproic acid [19].
• Birth defects related to bendectin use in pregnancy. I. Oral clefts and cardiac defects [20].

Biological context of Abnormalities

• Given that errors in meiotic maturation result in severe birth defects and are the most common cause of chromosomal aneuploidy and pregnancy loss in humans, studies of Fmn2 may provide a better understanding of infertility and birth defects [21].
• METHODS: We studied 42 infants from São Paulo, Brazil, who were exposed to misoprostol during the first 3 months of gestation, and then born with congenital abnormalities [22].
• We used information from the Group Health Cooperative of Puget Sound, Washington, USA, to evaluate the risk of birth defects in mothers exposed to topical tretinoin--a retinoid preparation used to treat acne--in the first trimester of pregnancy [23].
• Hemizygous interstitial deletions in human chromosome 22q11 are associated with velocardiofacial syndrome and DiGeorge syndrome and lead to multiple congenital abnormalities, including cardiovascular defects [24].
• These results define an epigenotype-phenotype relationship in BWS, in which aberrant methylation of H19 and LIT1 and UPD are strongly associated with cancer risk and specific birth defects [25].

Anatomical context of Abnormalities

• Synthetic retinoids chemically similar to vitamin A cause birth defects in humans; as in animals, the defects appear to affect tissues derived from the cranial neural crest [26].
• TCA-4 protein was not detected on the luminal surface of PLN HEVs in plt/plt mice, which have a congenital defect in T cell homing to PLNs [27].
• Affected individuals, who are males, suffer from infantile onset of epilepsy and hypocalcemia, which appears to be due to an isolated congenital defect of parathyroid gland development; females are not affected and are normocalcemic [28].
• Mutations in three members of the FGFR family have been found in patients with birth defects involving craniosynostosis (premature fusion of the cranial sutures) or skeletal abnormalities [29].
• Various mutations in the TBX5 gene have been identified in patients with Holt-Oram syndrome, which is characterized by congenital defects in the heart and upper extremities [30].

Gene context of Abnormalities

• Fanconi anaemia (FA) is an autosomal recessive inherited disorder associated with a progressive aplastic anaemia, diverse congenital abnormalities and cancer [31].
• Expression of a truncated Sall1 transcriptional repressor is responsible for Townes-Brocks syndrome birth defects [32].
• Mutations in mouse and human patched1 (ptc1) genes are associated with birth defects and cancer [33].
• In conclusion, this study demonstrates that gene-environment interactions cooperate to induce congenital defects through p53 activation [34].
• Mutations in mouse and human patched (PTCH) genes are associated with birth defects and cancer [35].

Analytical, diagnostic and therapeutic context of Abnormalities

• Epidemiologic studies of the risk of cancer and birth defects have been conducted in this group of workers, but little is known about the extent of their exposure to the 2,4,5-T contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent carcinogen in animals [36].
• To explore how birth defects epidemiology could benefit from these approaches, the authors compared them with a traditional case-control study design that evaluated the association between use of folic acid antagonists during the second and third pregnancy months and the risk of cardiovascular defects [37].
• METHODS: This was a case-control study within the Hungarian Case Control Surveillance of Congenital Abnormalities, 1980-1996, based on 22,843 newborn children or fetuses with congenital abnormalities and 38,151 children without any detected congenital abnormalities (the control group) [38].
• Safety of metronidazole during pregnancy: a cohort study of risk of congenital abnormalities, preterm delivery and low birth weight in 124 women [39].
• Immunotherapy and intranasal sodium cromoglycate (cromolyn) and beclo-methasone would be considered as first-line therapy, both because of their lack of association with congenital abnormalities and their superior efficacy to other agents [40].

References