Microcephaly in South Brazil: Are cases of Congenital Zika Syndrome increasing in recent years?

Northeast Brazil was the first region to detect a significant increase in babies born with microcephaly associated with prenatal zika virus infection in 2015. Rio Grande do Sul (RS) state was less impacted due to the temperate climate preventing the spread of the vector. This study investigated the prevalence and etiology of congenital microcephaly in RS in two different periods. This cross-sectional descriptive study included all live births with congenital microcephaly in RS from 2015 to 2022. Cases were divided into two groups: P1 "outbreak" (2015-16); and P2 "endemic" (2017-22). There were 58 cases of microcephaly (3.8/10,000) in P1 and 148 (1.97/10,000) in P2. Congenital Zika Virus infection was the etiology in 5.2% (n=3) in P1 and 6.7% (n=10) in P2. In conclusion, although the ZIKV outbreak in Brazil has receded, RS remains an area of concern, with a possible slight increase of live births with microcephaly secondary to ZIKV prenatal infection relative to the number of cases due to congenital infections. The broader distribution of the vector Aedes aegypti with warmer temperatures in our state might be linked to the increase in recent years. This study can be an alert to other regions of temperate or subtropical climates.

A New Strategy for the Old Challenge of Thalidomide: Systems Biology Prioritization of Potential Immunomodulatory Drug (IMiD)-Targeted Transcription Factors.

Several molecular mechanisms of thalidomide embryopathy (TE) have been investigated, from anti-angiogenesis to oxidative stress to cereblon binding. Recently, it was discovered that thalidomide and its analogs, named immunomodulatory drugs (IMiDs), induced the degradation of C2H2 transcription factors (TFs). This mechanism might impact the strict transcriptional regulation of the developing embryo. Hence, this study aims to evaluate the TFs altered by IMiDs, prioritizing the ones associated with embryogenesis through transcriptome and systems biology-allied analyses. This study comprises only the experimental data accessed through bioinformatics databases. First, proteins and genes reported in the literature as altered/affected by the IMiDs were annotated. A protein systems biology network was evaluated. TFs beta-catenin (CTNNB1) and SP1 play more central roles: beta-catenin is an essential protein in the network, while SP1 is a putative C2H2 candidate for IMiD-induced degradation. Separately, the differential expressions of the annotated genes were analyzed through 23 publicly available transcriptomes, presenting 8624 differentially expressed genes (2947 in two or more datasets). Seventeen C2H2 TFs were identified as related to embryonic development but not studied for IMiD exposure; these TFs are potential IMiDs degradation neosubstrates. This is the first study to suggest an integration of IMiD molecular mechanisms through C2H2 TF degradation.

Revealing the expression profile of genes that encode the Subcortical Maternal Complex in human reproductive failures.

The Subcortical Maternal Complex (SCMC) is composed of maternally encoded proteins required for the early stages of embryo development. Here we aimed to investigate the expression profile of the genes that encode the individual members of the SCMC in human reproductive failures. To accomplish that, we selected three datasets in the Gene Expression Omnibus repository for differential gene expression (DGE) analysis, comprising human endometrial and placental tissues of patients with recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL). The SCMC genes KHDC3L, NLRP2, NLRP4, NLRP5, OOEP, PADI6, TLE6, and ZBED3 were included in the DGE analysis, as well as CFL1 and CFL2 that connect the SCMC with the actin cytoskeleton. Additionally, differential co-expression analysis and systems biology analysis of gene-gene co-expression were performed for KHDC3L, NLRP5, OOEP, and TLE6, demonstrating gene pairs differentially correlated under the two conditions, and the co-expression with genes involved in immune response, cell cycle, DNA damage repair, embryo development, and male reproduction. Compared to control groups, NLRP5 demonstrated upregulation in the endometrium of RIF patients, and KHDC3L was upregulated in the fetal placental tissue of RPL patients, shedding light on the importance of considering SCMC genes in reproductive failures.

COVID-19 during pregnancy and adverse outcomes: Concerns and recommendations from The Brazilian Teratology Information Service.

SARS-CoV-2 virus was first identified in the beginning of 2020 and has spread all over the world, causing the Coronavirus Disease 2019 (COVID-19) pandemic. The virus is a member of the Coronavirus family, which includes viruses that cause common cold, Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). MERS and SARS are known by causing adverse events in pregnancy. Considering that SARS-CoV-2 is a new infection agent, little is known about the risk of its infection to human embryo/fetal development. However, SARS and MERS were associated with negative outcomes, such as miscarriage, preterm birth, intrauterine growth restriction and perinatal death. Here, we raise concerns and possibilities related the harmful potential of SARS-CoV-2 and COVID-19 to pregnancy, discussing symptoms, immunological changes during pregnancy, SARS-CoV-2 mutation rate (and the risks related to it). Finally, we point out recommendations to be performed by the scientific community and health care workers in order to identify and to manage potential risks to pregnant women and their babies.

Determining the pathogenicity of CFTR missense variants: Multiple comparisons of in silico predictors and variant annotation databases.

Pathogenic variants in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) are responsible for cystic fibrosis (CF), the commonest monogenic autosomal recessive disease, and CFTR-related disorders in infants and youth. Diagnosis of such diseases relies on clinical, functional, and molecular studies. To date, over 2,000 variants have been described on CFTR (~40% missense). Since few of them have confirmed pathogenicity, in silico analysis could help molecular diagnosis and genetic counseling. Here, the pathogenicity of 779 CFTR missense variants was predicted by consensus predictor PredictSNP and compared to annotations on CFTR2 and ClinVar. Sensitivity and specificity analysis was divided into modeling and validation phases using just variants annotated on CFTR2 and/or ClinVar that were not in the validation datasets of the analyzed predictors. After validation phase, MAPP and PhDSNP achieved maximum specificity but low sensitivity. Otherwise, SNAP had maximum sensitivity but null specificity. PredictSNP, PolyPhen-1, PolyPhen-2, SIFT, nsSNPAnalyzer had either low sensitivity or specificity, or both. Results showed that most predictors were not reliable when analyzing CFTR missense variants, ratifying the importance of clinical information when asserting the pathogenicity of CFTR missense variants. Our results should contribute to clarify decision making when classifying the pathogenicity of CFTR missense variants.

The natural history of pregnancies with prenatal diagnosis of Trisomy 18 or Trisomy 13: Retrospective cases of a 23-year experience in a Brazilian public hospital.

Trisomy 18 (T18) and trisomy 13 (T13) are polymalformative syndromes associated with a high rate of spontaneous abortions, intrauterine death, and short postnatal life. This study describes the overall outcome in a country where the therapeutic interruption of pregnancy is not available. The medical records of women with prenatal diagnosis of full trisomy of T13 or T18 between October 1994 and October 2017 were analyzed in order to describe their natural outcomes. Thirteen cases of T13 and 29 cases of T18 were included. The miscarriage rate was 9% for T18 and no cases for T13. Intrauterine fetal death occurred in 46% and 52% of cases for T13 and T18, respectively. The rate of live births for T13 was 54%, and the median survival was one day (95% CI -33.55 - 90.40) and 71% died in the first 24 hours of life. The rate of live births for T18 was 37% and the median survival was two days (95% CI -1.89 - 13.17); 90% of the affected babies died within first week of life. For the affected babies reaching the first year of life and for those who lived longer, multiple invasive and expensive procedures were required, without success in prolonging life beyond 180 days. This large series provides information for professionals and women regarding the natural histories of T13 and T18. Results of this study are consistent with those referenced in the literature, emphasizing the need of structured protocols and guidelines aiming early T13 and T18 diagnosis, prenatal care, gestation/parents follow-up, and counseling processes. For those couples with earlier diagnosis, a better follow-up and counseling during the prenatal care lead to the option for a support or palliative management of the newborn. Finally, when the counseling process is appropriate, it becomes easier to take decisions respecting the parent's autonomy and to look for better outcomes for both, the mother and the fetus.

From abortion-inducing medications to Zika Virus Syndrome: 27 years experience of the First Teratogen Information Service in Latin America.

In 1990, the first Teratogen Information Service in Brazil (SIAT) was implemented in the Medical Genetics Service at Hospital de Clinicas de Porto Alegre. SIAT is a free-to-use information service both to health professionals and the general population, especially to women who are pregnant or planning pregnancy. The main objective of this paper is to present the activities of SIAT in its initial years (1990-2006), compared to those in the last decade (2007-2017). In addition we review the scientific contribution of SIAT in the field of human teratogenesis. Since 1990, SIAT received 10,533 calls. Use of medications were the main reason for concern, accounting for 74% of all questions, followed by other chemical exposures (occupational, cosmetics, environmental), and maternal infectious diseases. Among its main contributions to scientific knowledge was the collaboration for the identification of two new human teratogens: misoprostol in the 1990s and Zika virus in 2015/16. In conclusion, SIAT is still evolving, as is the Medical Genetics Service that hosts it. Through its 27 years of existence more than 300 undergraduate and graduate students have rotated at SIAT. Presently, SIAT is expanding the research to experimental teratogenesis and to investigation of molecular mechanisms of teratogens.

Angiogenesis and oxidative stress-related gene variants in recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) affects ~3-5% of couples attempting to conceive and in around 50% of cases the aetiology remains unknown. Adequate vascularisation and placental circulation are indispensable for the development of a normal pregnancy. Prostaglandin-endoperoxide synthase 2 (PTGS2), vascular endothelial growth factor (VEGF) and the nitric oxide (NO) systems play important roles in reproductive physiology, participating in several steps including implantation and apoptosis of trophoblast cells. In this study we evaluated genetic polymorphisms in the inducible nitric oxide synthase (NOS2), PTGS2 and VEGFA genes as susceptibility factors for RPL. A case-control study was conducted in 149 women having two or more miscarriages and 208 controls. Allele and genotype distributions of the polymorphisms studied in the two groups were not statistically different. However, the dominant model showed that the presence of variant T (TT/GT) of rs2779249 (-1290G>T) of NOS2 was significantly associated with RPL (OR=1.58, CI 95%=1.03-2.44; P=0.037). The increased risk remained significant when adjusted for number of pregnancies, alcohol consumption and ethnicity (OR=1.92, CI95%=1.18-3.11; P=0.008). These results suggest that the variant genotypes of the functional polymorphism rs2779249 in the NOS2 promoter are a potential risk for RPL, possibly due to oxidative stress mechanisms.

Thalidomide embryopathy: Follow-up of cases born between 1959 and 2010.

BACKGROUND: Thalidomide is a known teratogen and it is estimated that more than ten thousand babies were affected by thalidomide embryopathy (TE), which is characterized mainly by limb defects, but can involve many organs and systems. Most people with TE were only evaluated at birth and it is not well established if thalidomide exposure during embryonic development leads to later effects. We analyzed the clinical history of adults with TE to better understand this gap in the clinical findings of TE. METHODS: Brazilian individuals with TE were invited to answer a clinical questionnaire which considered family history, social information, medical history, and current clinical and psychological health status. A clinical examination was also performed, including on the infant subjects to evaluate congenital anomalies. The characterization of the features was analyzed using descriptive statistics and Chi-square or Fisher's exact test. RESULTS: The congenital anomalies caused by thalidomide were reviewed in 28 Brazilian individuals, and the questionnaire was applied to the 23 adult subjects with TE (aged 19 to 55). Progressive deafness and dental loss were reported. From the comparison of TE individuals with the general Brazilian population, the early onset of cardiovascular diseases (p = 0.009) and a higher frequency of psychological disorders (p = 0.011) were observed. CONCLUSION: Although there is no sufficient evidence that thalidomide exposure caused or worsened the described events, this approach helps to better understand the TE phenotype, improves the clinical diagnosis, and can lead to adequate health support for these individuals.

Birth after low-level +20 Aneuploid Mosaic Embryo Transfer: A Case Report.

OBJECTIVE: Recently, it has been discussed whether or not mosaic embryo transfers should be performed since they might result in viable pregnancies, although they often end up being discarded. We report a case of successful pregnancy, after a mosaic embryo transfer from an in vitro matured egg and frozen PESA sperm. CASE DESCRIPTION: Tests performed on a female aged 40 years and a male aged 37 years seeking fertility treatment found she had an adequate ovarian reserve and patent fallopian tubes. He had a history of cryptorchidism and inguinal hernia repair. The spermogram showed azoospermia, and testicular ultrasound showed an atrophic left testicle and a normal right testis. The vas deferens was palpated during physical examination. Intracytoplasmic sperm injection with percutaneous epididymal sperm aspiration (PESA) was indicated. Two cycles of IVF after controlled ovarian stimulation with follitropin delta was performed. In the first cycle, seven mature eggs were inseminated, two fertilized normally, resulting in one blastocyst biopsied and analyzed by NGS with complex aneuploid results. In the second cycle, frozen sperm from PESA was used. Three eggs were inseminated on the day of the procedure (resulting in 2 blastocysts), and three in vitro matured eggs were inseminated after 24 hours (resulting in 1 blastocyst). NGS analysis showed two complex aneuploid embryos and one 40% low-level trisomy 20 aneuploid mosaicism (+20) for the post 24-hour embryo. A mosaic embryo transfer was performed, resulting in clinical pregnancy and birth of a healthy baby girl with a normal blood karyotype. DISCUSSION: Mosaic embryo transfer is a topic for discussion. Certain levels of mosaicism do not seem to pose risks to the development of the fetus.

Caffeine intake during pregnancy and adverse outcomes: An integrative review.

Caffeine intake during pregnancy is common. Caffeine crosses the placenta, raising concerns about its possible deleterious effects on the developing embryo/fetus. Studies on this subject show conflicting results, and still there is no consensus on the recommended dose of caffeine during pregnancy. We performed an integrative review with studies from six databases, using broad MESH terms to allow the identification of publications that addressed the outcomes of caffeine use during pregnancy, with no date limit for publications, in English and Portuguese language. The research returned 16,192 articles. After removing duplicates, screening by title, abstract and full-text, we evaluated 257 and included 59 articles. We found association between caffeine intake and pregnancy loss, low birth weight, cardiac and genital anomalies, higher body mass, and neurodevelopmental and neurobehavioral outcomes. The effects were often dose dependent. No association with prematurity has been demonstrated, but one study showed a small reduction in gestational age with increasing doses of caffeine intake. Defining a safe dose for caffeine intake during pregnancy is a challenging task due to the heterogeneity in study designs and results, as well as the difficulty of reliably assessing the amount of caffeine consumed. In some studies, exposures below the recommended level of caffeine intake during pregnancy (200 mg/day), as suggested by the guidelines, were associated with pregnancy loss, low birth weight, cardiac and genital anomalies, higher body mass, and neurodevelopmental and neurobehavioral outcomes. Well-designed studies with reliable quantification of caffeine intake are needed to assess the safety of low doses during pregnancy.

Polymorphisms in the endothelial nitric oxide synthase gene in thalidomide embryopathy.

Thalidomide is one of the most potent teratogens known to humans. It is currently used for many clinical situations such as treatment of leprosy reactions and multiple myeloma. However, the teratogenic mechanisms by which it produces morphological defects still remain unclear. One of the hypotheses is the blockage of angiogenesis by reduction of nitric oxide (NO). In this study, we evaluated two functional polymorphisms of the endothelial nitric oxide synthase (eNOS) gene which is a constitutively expressed enzyme responsible for production of NO. The promoter -786T>C exon 7 (896G>T) polymorphisms were genotyped using real-time PCR for 28 individuals with thalidomide embryopathy (TE), 27 first-degree relatives of these individuals, and 68 individuals from the general population. Their allele, genotypic, and haplotypic frequencies were compared. A significant difference was observed in the -786T>C polymorphism genotypes (p=0.03) between the groups affected by TE and those unaffected (non-relatives). The TT genotype of the 896G>T polymorphism was observed in 10.7% of those affected and 2.9% of those unaffected, but the difference was not statistically significant (p=0.09). The haplotypic analysis indicated that the wild haplotype -786T/896G was distributed differently in the affected and unaffected groups (p=0.004). These results indicate that the individuals with TE have a higher frequency of alleles associated with lower expression of eNOS, indicating that this may be a genotype susceptible to TE.

Expression profiles of meiotic genes in male vs. female gonads and gametes: Insights into fertility issues.

Gametes are specialized cells that, at fertilization, give rise to a totipotent zygote capable of generating an entire organism. Female and male germ cells undergo meiosis to produce mature gametes; however, sex-specific events of oogenesis and spermatogenesis contribute to specific roles of gametes in reproductive issues. We investigate the differential gene expression (DGE) of meiosis-related genes in human female and male gonads and gametes in normal and pathological conditions. The transcriptome data for the DGE analysis was obtained through the Gene Expression Omnibus repository, comprising human ovary and testicle samples of the prenatal period and adulthood, additionally to male (non-obstructive azoospermia (NOA) and teratozoospermia), and female (polycystic ovary syndrome (PCOS) and advanced maternal age) reproductive conditions. Gene ontology terms related to meiosis were associated with 678 genes, of which 17 genes in common were differentially expressed between the testicle and ovary during the prenatal period and adulthood. Except for SERPINA5 and SOX9, the 17 meiosis-related genes were downregulated in the testicle during the prenatal period and upregulated in adulthood compared to the ovary. No differences were observed in the oocytes of PCOS patients; however, meiosis-related genes were differentially expressed according to the patient's age and maturity of the oocyte. In NOA and teratozoospermia, 145 meiosis-related genes were differentially expressed in comparison to the control, including OOEP; despite no recognized role in male reproduction, OOEP was co-expressed with genes related to male fertility. Taking together, these results shed light on potential genes that might be relevant to comprehend human fertility disorders.

High-risk twin pregnancy: case report of an adolescent patient with cystic fibrosis and systemic lupus erythematosus.

BACKGROUND: We present the first case to our knowledge of a spontaneous twin pregnancy in a 16-year-old Caucasian patient with cystic fibrosis and systemic lupus erythematosus. Cystic fibrosis is one of the most common autosomal recessive genetic disorders and primarily affects the respiratory and digestive systems. Systemic lupus erythematosus is a chronic inflammatory disease of unknown cause that affects nearly every organ. Patients with cystic fibrosis or systemic lupus erythematosus are progressively having longer life expectancy and better quality of life, which has led a greater number of female patients reporting the desire to become mothers. CASE PRESENTATION: We present a case of a Caucasian 16-year-old pregnant with twins being treated for both cystic fibrosis and systemic lupus erythematosus. She has two CFTR mutations: p.F508del and 1812_1G>A. In the second trimester, she was admitted for possible preterm labor, which was successfully stopped. The patient's nutritional status worsened, and she had a pulmonary exacerbation as well as a flare of systemic lupus erythematosus. At the 28th gestational week, she presented with a massive hemoptysis episode. The cesarean delivery had no complications, and there were no serious immediate postpartum complications. DISCUSSION AND CONCLUSIONS: While adolescent pregnancies in and of themselves are considered high risk for both the young mothers and their children, they are further complicated when the mother has two chronic diseases and a twin pregnancy. We achieved positive results using a multidisciplinary approach; however, the risks involved were so high that major efforts are to be taken by our medical community to prevent unplanned pregnancies in all patients with cystic fibrosis, especially when a serious comorbidity like the one in this case is present.

Genetic and in silico analysis show a role of SMAD3 on recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) is one of the most common reproductive failures affecting 1-5% of couples. Smad3 is an effector of signalling of the Transforming Growth Factors-ß superfamily (TGF-ß), regulating the transcription of several target genes of these cytokines. The objective of this study was to evaluate the influence of a variant on SMAD3 (rs17293443) in RPL. A case-control study was carried out with 149 women who experienced RPL and 159 controls, as well as bioinformatics tools to determine the role of this variant in this condition. Our study showed an allelic (p = 0.023) and genotypic (p < 0.01) association of this variant with the RPL. Our functional in silico predictions suggest that this variant causes a change in SMAD3 expression levels. Alterations in the expression of this gene can directly compromise the Smad3-dependent signalling pathway that is fundamental for key processes for gestation such as steroid hormone regulation and implantation, as demonstrated by ontologies analyses performed and the literature. Our findings regarding the involvement of Smad3 on RPL are a novelty in this field, and they seem to be promising to the clinical management of this condition.

Prevalence of thrombophilia-associated genetic risk factors in blood donors of a regional hospital in southern Brazil.

INTRODUCTION: Thromboembolic events occur due to an imbalance in the hemostasis and some factors associated with this condition can be inherited. In order to evaluate the frequency of genotypes considered to be common hereditary risk factors for thrombophilia associated with venous thrombosis (g.1691G > A and g.20210G > A) and hyperhomocysteinemia (g.677C > T and g.1298A > C), samples from voluntary healthy blood donors at the Hospital de Clínicas de Porto Alegre were tested. METHODS: We examined 325 blood samples from blood donors collected from October 2017 to July 2018. Blood was collected on filter paper and the DNA was extracted for single nucleotide polymorphisms (SNPs) analysis using the qualitative real time polymerase chain reaction. RESULTS: The calculated frequencies of each genetic variant in heterozygosity were 4% for the FV gene (g.1691G > A), 4% for the F2 gene (g.20210G > A) and 42% and 39% for methylenetetrahydrofolate reductase (MTHFR), g.677C > T and g.1298A > C, respectively. Only the genetic variants of MTHFR were found in homozygosity, with frequencies of 14% and 6% (g.677C > T and g.1298A > C), respectively. DISCUSSION: Altogether, these results describe the frequencies of genetic variants associated with venous thrombosis and hyperhomocysteinemia in the analyzed group and are important to enhance our current knowledge about the genetic profiles of Brazilian blood donors.

List of priority congenital anomalies for surveillance under the Brazilian Live Birth Information System. / Lista de anomalias congênitas prioritárias para vigilância no âmbito do Sistema de Informações sobre Nascidos Vivos do Brasil.

OBJECTIVE: To define the list of priority congenital anomalies for improving their recording on the Brazilian Live Birth Information System (Sinasc). METHODS: Based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), international protocols and meetings with specialists, the list of priority anomalies was built considering two main criteria: being diagnosable at birth and having intervention available at different levels. The list was submitted for consideration by the Brazilian Medical Genetics and Genomics Society. RESULTS: The list comprised eight groups of congenital anomalies distributed according to the type of related anomaly, as well as the affected part of the body and its corresponding code in ICD-10 Chapter XVII. CONCLUSION: The list of priority congenital anomalies for notification provides a basis for improving case recording on Sinasc.

Further characterization of microdeletion syndrome involving 2p15-p16.1.

We report on a patient presenting with cognitive delay, prenatal and postnatal growth deficiency, microcephaly, ptosis of eyelids, high and broad nasal root, and camptodactyly. Analysis of a dense whole genome single-nucleotide polymorphism (SNP) array showed a de novo 3.35 Mb deletion on 2p15-p16.1. In order to study the parental origin of the deletion we analyzed selected SNPs in the deleted area in the proband and her parents showing Mendelian incompatibilities suggesting a de novo deletion on the chromosome of paternal origin. Based on the five cases described previously in the literature, we have narrowed the critical region responsible for the 2p15-p16.1 microdeletion syndrome phenotype. The critical region does not include the VRK2 gene that had been speculated to have a role in cortical dysplasia. However, the association of the VRK2 gene with cortical dysplasia remains to be determined, as MRI imaging of the brain and gene content of the 2p15-16 deletion becomes established in more patients.

CRL4-Cereblon complex in Thalidomide Embryopathy: a translational investigation.

The Cereblon-CRL4 complex has been studied predominantly with regards to thalidomide treatment of multiple myeloma. Nevertheless, the role of Cereblon-CRL4 in Thalidomide Embryopathy (TE) is still not understood. Not all embryos exposed to thalidomide develop TE, hence here we evaluate the role of the CRL4-Cereblon complex in TE variability and susceptibility. We sequenced CRBN, DDB1, CUL4A, IKZF1, and IKZF3 in individuals with TE. To better interpret the variants, we suggested a score and a heatmap comprising their regulatory effect. Differential gene expression after thalidomide exposure and conservation of the CRL4-Cereblon protein complex were accessed from public repositories. Results suggest a summation effect of Cereblon variants on pre-axial longitudinal limb anomalies, and heatmap scores identify the CUL4A variant rs138961957 as potentially having an effect on TE susceptibility. CRL4-Cereblon gene expression after thalidomide exposure and CLR4-Cereblon protein conservation does not explain the difference in Thalidomide sensitivity between species. In conclusion, we suggest that CRL4-Cereblon variants act through several regulatory mechanisms, which may influence CRL4-Cereblon complex assembly and its ability to bind thalidomide. Human genetic variability must be addressed not only to further understand the susceptibility to TE, but as a crucial element in therapeutics, including in the development of pharmacogenomics strategies.

Congenital anomalies from the health surveillance perspective: compilation of a list based on ICD-10. / Anomalias congênitas na perspectiva da vigilância em saúde: compilação de uma lista com base na CID-10.

OBJECTIVE: To propose a list of congenital anomalies having corresponding codes in the International Statistical Classification of Diseases and Related Health Problems, 10thRevision (ICD-10), with the aim of applying it in health surveillance. METHODS: In December 2019, the following data sources were searched: ICD-10; ICD-11; anomalies monitored by three surveillance programs; and a database of rare diseases (Orphanet). Anomalies were retrieved from these data sources, processed to check for correspondence with ICD-10 and reviewed manually to compile the list. RESULTS: 898 codes were identified, of which 619 (68.9%) were contained in ICD-10 Chapter XVII. Of the 279 codes contained in other chapters, 19 were exclusive to the ICD-11 search, 72 to the surveillance programs, 79 to Orphanet and 36 to the search for terms in ICD-10. CONCLUSION: The codes contained in ICD-10 Chapter XVII do not capture the totality of congenital anomalies, indicating the need to adopt an expanded list.