Conjoined twins (CT) are a very rare developmental accident of uncertain etiology. Prevalence has been previously estimated to be 1 in 50,000 to 1 in 100,000 births. The process by which monozygotic twins do not fully separate but form CT is not well understood. The purpose of the present study was to analyze diverse epidemiological aspects of CT, including the different variables listed in the Introduction Section of this issue of the Journal. The study was made possible using the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) structure. This multicenter worldwide research includes the largest sample of CT ever studied. A total of 383 carefully reviewed sets of CT obtained from 26,138,837 births reported by 21 Clearinghouse Surveillance Programs (SP) were included in the analysis. Total prevalence was 1.47 per 100,000 births (95% CI: 1.32-1.62). Salient findings including an evident variation in prevalence among SPs: a marked variation in the type of pregnancy outcome, a similarity in the proportion of CT types among programs: a significant female predominance in CT: particularly of the thoracopagus type and a significant male predominance in parapagus and parasitic types: significant differences in prevalence by ethnicity and an apparent increasing prevalence trend in South American countries. No genetic, environmental or demographic significant associated factors were identified. Further work in epidemiology and molecular research is necessary to understand the etiology and pathogenesis involved in the development of this fascinating phenomenon of nature.

The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by con-genital anomaly register and region. Twenty-four population- and hospital-based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data-reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI1.3–2.06), and for T18 was 4.08 (95% CI 3.01–5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38–0.72), and for T18 was 1.07 (95% CI 0.77–1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1-year follow-up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions.

Background Myelomeningocele (MMC) is the most severe and frequent type of spina bifida. Its etiology remains poorly understood. The Hedgehog (Hh), Wnt, and planar cell polarity (PCP) signaling pathways are essential for normal tube closure, needing a structural‐functional cilium for its adequate function. The present study aimed to investigate the impact of different gene variants (GV) from those pathways on MMC genotype‐subphenotype correlations. Methods The study comprised 500 MMC trios and 500 controls, from 16 Telethon centers of 16 Mexican states. Thirty‐four GVs of 29 genes from cilia, Hh, PCP, and Wnt pathways, were analyzed, by an Illumina on design microarray. The total sample (T‐MMC) was stratified in High‐MMC (H‐MMC) when thoracic and Low‐MMC (L‐MMC) when lumbar‐sacral vertebrae affected. STATA/SE‐12.1 and PLINK software were used for allelic association, TDT, and gene–gene interaction (GGI) analyses, considering p value <.01 as statistically significant differences (SSD). Results Association analysis showed SSD for COBL‐rs10230120, DVL2‐rs2074216, PLCB4‐rs6077510 GVs in T‐MMC and L‐MMC, and VANGL2‐rs120886448 in T‐MMC and H‐MMC, and INVS‐rs7024375 exclusively in L‐MMC. TDT assay showed SSD preferential transmissions of C2CD3‐rs826058 in H‐MMC, and LRP5‐rs3736228, and BBS2‐rs1373 in L‐MMC. Statistically significant GGI was observed in four in T‐MMC, four completely different in L‐MMC, and one in H‐MMC. Interestingly, no one repeated in subphenotypes. Conclusions Our results support an association of GVs in Hh, Wnt, PCP, and cilia pathways, with MMC occurrence location, although further validation is needed. Furthermore, present results show a distinctive panel of gene‐variants in H‐MMC and LMMC subphenotypes, suggesting a feasible genotype–phenotype correlation.

OEIS is the acronym of a malformations complex association including omphalocele, exstrophy of bladder or cloaca, imperforate anus, and spinal defects. It has a very low prevalence, ranging from 1/82,000 to 1/200,000 live births (LB). The etiology of OEIS is unknown. Virtually all cases are sporadic, and specific associated risk factors uncertain.ObjectivesThis study aimed to determine the prevalence, clinical spectrum, possible early pregnancy exposures, and demographic characteristics as potentially associated risk factors in a sample of Mexican cases.MethodsWe conducted a multihospital based case–control study on 12 cases with the OEIS complex identified in 1,195,020 LB born from January 1978 to December 2015. All comparisons performed were matching 1:3 the relation of cases and controls, respectively, considering the p‐value of ≤.05 as statistically significant.ResultsThe prevalence of OEIS was 1.004/100,000 (1/99,585) LB. The frequency of bladder/cloacal exstrophy was 75 and 25%, respectively, omphalocele was 83.3%, and imperforate anus and spinal defects, 75.0% each. Two pairs of twins discordant for the defect exhibited the severest OEIS phenotype. Except for the higher frequency of maternal first pregnancy trimester influenza infection, early perinatal mortality and a twining trend association, none other variable differed significantly.DiscussionThe prevalence of OEIS in our sample is within the highest reported worldwide. First‐trimester pregnancy maternal influenza infection and twining emerge as associated risk factors for OEIS. Although twin zygosity was not defined, the observed severest phenotypes in twins endorse the hypothesis that OEIS and monozygotic twinning are features of disturbances on early blastogenesis.

The understanding of genetic and environmental determinants in the Mexican population is important for other Latin American populations as well, living in their own countries or moving to other ones, particular due to the current migration characteristics and particular genetic background like the Mexican Mestizo and other Central American populations with similar characteristics and migrating to neighbor developed countries, introducing their own smoking behavior and contributing importantly to the genetic pool of the receptor country.

Our results show the teratogenicity of epilepsy by itself, the synergistic effect of some anticonvulsants, and the need of an appropriate periconceptional control of the disease and treatment.

Background: Severe congenital neutropenia type 4 (SCN4) is a rare autosomal recessive granulopoiesis disorder caused by G6PC3 gene pathogenic variants. The estimated prevalence is 1/10,000,000 people. Over 90% of patients present a syndromic form with variable multisystemic involvement, including congenital heart defects, increased visibility of superficial veins (IVSV), inflammatory bowel disease, and congenital urogenital defects as prominent symptoms. Objectives: The objective of the study was to study non-hematological phenotypic findings that suggest a clinical diagnosis of SCN4. Methods: We examined medical records of patients diagnosed with neutropenia from January 2000 to December 2020, selecting cases with nonhematologic manifestations for phenotypic description and G6PC3 gene sequencing. Results: We found 11 cases with nonhematologic features: congenital heart defects in 8, IVSV in 6, inflammatory bowel disease in 4, urogenital defects in 4, and similar facial appearance. In addition, Sanger sequencing confirmed 3 homozygous cases for the c.210delC variant, a compound heterozygous harboring this variant, and a c.199_218+1 deletion. Conclusions: Our findings of the c.210delC variant in very close geographical settings, to date, have only been reported among Mexicans, and a mutual uncommon surname in two families strongly supports a founder effect for the variant in the studied population. Furthermore, the described non-hematologic symptoms in patients with severe primary neutropenia should be explored, confirming SCN4 by investigating G6PC3 gene mutations.

Isolated postaxial polydactyly (I-PAP), as a single defect, is a frequent malformation, characterized by an extra digit placed on the ulnar or fibular side of the limbs. Worldwide prevalence varies from as high as 225/10,000 in Nigerians to so low as 6.08/10,000 in Argentinians. Genetic-ethnic background significantly affects worldwide prevalence and type of I-PAP. Herein we describe the epidemiological characteristics of I-PAP in 697 newborns, 383 males and 314 females identified in 1,178,993 examined live births from a multicenter case-control hospital-based population study, the Mexican program of Registry and Epidemiological Surveillance of Congenital Malformations (RYVEMCE). The main characteristics analyzed included total I-PAP, stratified in Types A and B, defined as complete or incomplete extra-digitformation, respectively, sex prevalence, affected limb, laterality, parity, prematurity, delivery-type, twinning, consanguinity, and parental age. Males (6.35/10,000) are significantly more frequently affected than females (5.45/10,000), hands more than feet, left more than right limbs, and Type B (74.50%) more than A (25.50%). Prematurity and forceps use were significantly more frequent in cases than controls. An evident decreasing time-trend prevalence was present. Similar findings with other studies were males, upper and left limbs more frequently affected. Findings that were not previously reported include prematurity, forceps use, a significant decreasing time trend and an inverse ethnic prevalence for Types A (75%) and B (25%) in the Mayan population in contrast to other worldwide ethnic groups. K E Y W O R D S epidemiologic characteristics, isolated postaxial polydactyly, multicenter study