Explore the vast range of titles available.

In 1998, fortification of cereal products with folic acid became mandatory in Canada. The authors assessed the prevalence of neural-tube defects in seven Canadian provinces before and after the implementation of folic acid fortification; they found that the rate of defects was reduced almost by half and that the magnitude of reduction was proportional to the prefortification baseline rate in each province. These data are evidence of beneficial effects of food fortification with folic acid on rates of neural-tube defects in Canada. The authors assessed the prevalence of neural-tube defects before and after the implementation of folic acid fortification in Canada. The rate of defects was reduced almost by half. The benefit of folic acid supplementation during the periconception period in reducing the risk of neural-tube defects in offspring has been demonstrated both in experimental and in observational studies. 1 Fortification of many cereal-food products became mandatory in the United States on January 1, 1998, and the Canadian milling industry started fortification early in 1997, to meet the U.S. requirements for imported flour. 2 On November 11, 1998, fortification with folic acid of all types of white flour, enriched pasta, and cornmeal became mandatory in Canada. 3 The goal of fortification was to increase by approximately 30 to 70% the average intake of . . .

Current published long-term provincial or territorial congenital anomaly data are lacking for Canada. We report on prevalence (per 1000 total births) and trends in 1997-2019, in Alberta, Canada, for selected congenital anomalies. Associated risk factors are also discussed. We used data from the Alberta Congenital Anomalies Surveillance System (ACASS) to calculate the prevalence and perform chi-square linear trend analyses. From 1997 to 2019, the overall prevalence of neural tube defects was stable, at 0.74 per 1000 total births. The same was true for spina bifida (0.38), orofacial clefts (1.99), more severe CHDs (transposition of the great arteries, 0.38; tetralogy of Fallot, 0.33; and hypoplastic left heart syndrome, 0.32); and gastroschisis (0.38). Anencephaly, cleft palate and anorectal malformation significantly decreased with a prevalence of 0.23, 0.75 and 0.54 per 1000 total births, respectively. Significantly increasing trends were reported for anotia/microtia (0.24), limb reduction anomalies (0.73), omphalocele (0.36) and Down syndrome (2.21) and for hypospadias and undescended testes (4.68 and 5.29, respectively, per 1000 male births). Congenital anomalies are an important public health concern with significant social and societal costs. Surveillance data gathered by ACASS for over 40 years can be used for planning and policy decisions and the evaluation of prevention strategies. Contributing genetic and environmental factors are discussed as is the need for continued surveillance and research.

BackgroundAxenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, with or without systemic features. The discovery of causative genes identified ARS subtypes with distinct phenotypes, but our understanding is incomplete, complicated by the rarity of the condition.MethodsGenetic and phenotypic characterisation of the largest reported ARS cohort through comprehensive genetic and clinical data analyses.Results128 individuals with causative variants in PITX2 or FOXC1, including 81 new cases, were investigated. Ocular anomalies showed significant overlap but with broader variability and earlier onset of glaucoma for FOXC1-related ARS. Systemic anomalies were seen in all individuals with PITX2-related ARS and the majority of those with FOXC1-related ARS. PITX2-related ARS demonstrated typical umbilical anomalies and dental microdontia/hypodontia/oligodontia, along with a novel high rate of Meckel diverticulum. FOXC1-related ARS exhibited characteristic hearing loss and congenital heart defects as well as previously unrecognised phenotypes of dental enamel hypoplasia and/or crowding, a range of skeletal and joint anomalies, hypotonia/early delay and feeding disorders with structural oesophageal anomalies in some. Brain imaging revealed highly penetrant white matter hyperintensities, colpocephaly/ventriculomegaly and frequent arachnoid cysts. The expanded phenotype of FOXC1-related ARS identified here was found to fully overlap features of De Hauwere syndrome. The results were used to generate gene-specific management plans for the two types of ARS.ConclusionSince clinical features of ARS vary significantly based on the affected gene, it is critical that families are provided with a gene-specific diagnosis, PITX2-related ARS or FOXC1-related ARS. De Hauwere syndrome is proposed to be a FOXC1opathy.

Anterior segment dysgenesis (ASD) encompasses a broad spectrum of developmental conditions affecting anterior ocular structures and associated with an increased risk for glaucoma. Various systemic anomalies are often observed in ASD conditions such as Axenfeld-Rieger syndrome (ARS) and De Hauwere syndrome. We report DNA sequencing and copy number analysis of PITX2 and FOXC1 in 76 patients with syndromic or isolated ASD and related conditions. PITX2 mutations and deletions were found in 24 patients with dental and/or umbilical anomalies seen in all. Seven PITX2-mutant alleles were novel including c.708_730del, the most C-terminal mutation reported to date. A second case of deletion of the distant upstream but not coding region of PITX2 was identified, highlighting the importance of this recently discovered mechanism for ARS. FOXC1 deletions were observed in four cases, three of which demonstrated hearing and/or heart defects, including a patient with De Hauwere syndrome; no nucleotide mutations in FOXC1 were identified. Review of the literature identified several other patients with 6p25 deletions and features of De Hauwere syndrome. The 1.3-Mb deletion of 6p25 presented here defines the critical region for this phenotype and includes the FOXC1, FOXF2, and FOXQ1 genes. In summary, PITX2 or FOXC1 disruptions explained 63% of ARS and 6% of other ASD in our cohort; all affected patients demonstrated additional systemic defects with PITX2 mutations showing a strong association with dental and/or umbilical anomalies and FOXC1 with heart and hearing defects. FOXC1 deletion was also found to be associated with De Hauwere syndrome.

Townes‐Brocks syndrome is an autosomal dominantly inherited disorder, which comprises multiple birth defects including renal, ear, anal, and limb malformations. TBS has been shown to result from mutations in SALL1, a human gene related to the developmental regulator SAL of Drosophila melanogaster. The SALL1 gene product is a zinc finger protein thought to act as a transcription factor. It contains four highly conserved, evenly distributed C2H2 double zinc finger domains. A single C2H2 motif is attached to the second domain, and at the amino terminus SALL1 contains a C2HC motif. Most mutations causing TBS are clustered in the N‐terminal third of the SALL1 coding region and result in the production of truncated proteins containing only one or none of the C2H2 domains and the N‐terminal transcriptional repressor domain of SALL1. Twenty‐three SALL1 mutations were reported prior to this work, 22 of which are located in exon 2, 5′ of the second double zinc finger‐encoding region. Here we present 12 novel mutations in SALL1 associated with Townes‐Brocks syndrome in 13 unrelated families. These include three nonsense mutations, three short insertions and six short deletions. Thus the number of SALL1 mutations increases to 35. Rare phenotypical features among mutation positive patients include hypothyroidism, vaginal aplasia with bifid uterus, cryptorchidism, bifid scrotum without hypospadia scrotalis, unilateral chorioretinal coloboma with loss of vision, dorsal hypoplasia of the corpus callosum, and umbilical hernia. © 2005 Wiley‐Liss, Inc.

Introduction.On manque de données provinciales ou territoriales à long terme publiées et actuelles sur les anomalies congénitales Au Canada. Cette étude fait état de la prévalence (pour 1000 naissances totales) et des tendances pour diverses anomalies congénitales de 1997 à 2019 en Alberta (Canada). Les facteurs de risque associés sont également abordés.Méthodologie. Nous avons utilisé les données du Système de surveillance des anomalies congénitales de l’Alberta (ACASS) pour calculer la prévalence et effectuer des analyses de tendance linéaire par test du chi carré.Résultats. Entre 1997 et 2019, la prévalence globale des anomalies du tube neural est demeurée stable, à 0,74 pour 1000 naissances totales. C’était également le cas pour le spina bifida (0,38), les fentes orofaciales (1,99), les cardiopathies congénitales graves (transposition des grandes artères, 0,38; tétralogie de Fallot, 0,33; hypoplasie du cœur gauche, 0,32) et le gastroschisis (0,38). L’anencéphalie, la fente palatine et les anomalies anorectales ont diminué significativement, avec une prévalence de respectivement 0,23, 0,75 et 0,54 pour 1000 naissances totales. Une tendance significativement à la hausse a été relevée pour l’anotie/microtie (0,24), les anomalies de raccourcissement des membres (0,73), l’omphalocèle (0,36) et le syndrome de Down (2,21), ainsi que pour l’hypospadias et la cryptorchidie (respectivement 4,68 et 5,29 pour 1 000 naissances masculines).Conclusion.Les anomalies congénitales constituent un important problème de santé publique, qui est associé à des coûts sociaux et sociétaux substantiels. Les données de surveillance recueillies par l’ACASS sur plus de 40 ans peuvent servir à la planification et aux décisions en matière de politiques ainsi qu’à l’évaluation des stratégies de prévention. Les facteurs génétiques et environnementaux contributifs sont abordés, de même que la nécessité de poursuivre la surveillance et la recherche.

Objective To determine the prevalence and trends of orofacial clefts in Alberta (Canada) over a 33-year period (1980 through 2011) and to determine whether the trends differ for subcategories of orofacial clefts for the period from 1997 through 2011. Design A prevalence study based on the Alberta Congenital Anomalies Surveillance System, which has multiple sources of ascertainment, capability of verification, and an upper age limit of 1 year. Inclusion All live born and stillborn babies and fetal deaths less than 20 weeks' gestation (including terminations of pregnancy) born in Alberta of mothers who reside in Alberta. Results and Conclusions Rates for cleft lip with or without cleft palate and cleft palate only have been very stable over the 33-year period (1980 through 2011). These rates include all clefts (isolated, syndromes, recognizable conditions, chromosomal and multiple congenital anomalies). Ascertainment of fetal deaths less than 20 weeks' gestation began in 1997. There are trends for the 1997 through 2011 cohort with a marginally significant increase for cleft lip with or without cleft palate in the isolated category and a significant decrease for cleft palate, mainly in the associated groups. The impact of folic acid fortification and/or multivitamins/folic acid supplementation reports in the literature have shown no consensus with respect to a change in the prevalence of orofacial clefts. It is unclear whether folic acid fortification has had any impact in Alberta.

Objectives: Fortification of grain products with folic acid has been shown to significantly reduce the occurrence of neural tube defects (NTDs) in Canada and elsewhere. However, the impact on non-NTD anomalies has not been well studied. Methods: Using the Alberta Congenital Anomalies Surveillance System (ACASS), we examined changes in occurrence of select congenital anomalies where folic acid supplementation with multivitamins had previously been suggested to have an effect. Anomalies documented in the ACASS 1992-1996 (pre-fortification) were compared to 1999-2003 (post-fortification). Results: A significant decrease in spina bifida (OR 0.51, 95% CI 0.36-0.73) and ostium secundum atrial septal defects (OR 0.80, 95% CI 0.69-0.93) was evident, but there was a significant increase in obstructive defects of the renal pelvis and ureter (OR 1.45, 95% CI 1.24-1.70), abdominal wall defects (OR 1.40, 95% CI 1.04-1.88) and pyloric stenosis (OR 1.49, 95% CI 1.18-1.89). Conclusions: Consistent with other studies, a 50% reduction in spina bifida was associated with the post-fortification time period. Supporting the possibility that folic acid fortification may play a role in preventing other birth defects, a 20% reduction in atrial septal defects was also associated. The increase in abdominal wall defects, most notably gastroschisis, is likely related to pre-existing increasing trends documented in several regions around the world. The increase in pyloric stenosis and obstructive urinary tract defects was not expected and any causal relationship with folic acid fortification remains unclear. Similar studies by other birth defects surveillance systems in Canada and elsewhere are needed to confirm these trends. Objectifs : II est prouvé que l'enrichissement en acide folique des produits céréaliers réduit la fréquence des anomalies du tube neural (ATN) au Canada et ailleurs dans le monde. Cependant, l'impact d'un apport supplémentaire en acide folique sur les autres anomalies congénitales n'a pas été suffisamment étudié. Méthode : À l'aide du système de surveillance des anomalies congénitales de l'Alberta (ACASS), nous avons examiné les variations dans la fréquence de certaines anomalies congénitales pour lesquelles on pense qu'une supplementation multivitaminique contenant de l'acide folique aurait un effet. Les anomalies répertoriées dans l'ACASS de 1992 à 1996 (avant l'enrichissement) ont été comparées aux données de 1999-2003 (après l'enrichissement). Résultats : Des baisses significatives du spina bifida (RC=0,51, IC de 95 % = 0,36-0,73) et de la persistance de l'ostium secundum [variété la plus fréquente de communication interauriculaire] (RC=0,80, IC de 95 % = 0,69-0,93) ont été observées, avec par contre des augmentations significatives des malformations obstructives du bassinet du rein et de l'uretère (RC=1,45, IC de 95 % = 1,24-1,70), des malformations de la paroi abdominale (RC=1,40, IC de 95 % = 1,04-1,88) et de la sténose du pylore (RC=1,49, IC de 95 % = 1,18-1,89). Conclusion : Conformément aux résultats d'autres études, une diminution de 50 % dans la fréquence du spina bifida était associée à la période suivant l'enrichissement en acide folique. Un tel enrichissement pourrait jouer un rôle dans la prévention d'autres anomalies congénitales, comme en témoigne Ici baisse de 20 % dans la fréquence de la communication interauriculaire. L'augmentation des malformations de la paroi abdominale, en particulier du laparoschisis, est probablement liée à des tendances haussières préexistantes signalées dans plusieurs régions du monde. Les augmentations de la sténose du pylore et des malformations obstructives du tractus urinaire n'étaient pas prévues, mais une relation causale entre ces anomalies et l'enrichissement en acide folique n'est pas encore établie. Il faudrait mener des études semblables à partir d'autres systèmes de surveillance des anomalies congénitales au Canada et ailleurs dans le monde pour confirmer ou infirmer ces tendances.

Congenital anomalies (CA) are present in approximately 3% of all newborn babies and account for about 12% of paediatric hospital admissions. They represent an important public health problem. Surveillance is especially important so that preventive measures such as folie acid fortification can be properly assessed without resorting to a series of ad hoc studies. Canada's surveillance of CAs is weak, with only Alberta and British Columbia having established sytems. Most provinces have perinatal systems but their CA data are incomplete and they do not capture terminations of pregnancy. The same is true of the Public Health Agency of Canada's system. A new system, the Fetal Alert Network, has been proposed for Ontario, which represents a start but will require additional sources of ascertainment if it is to be a truly population-based system for Ontario. Des anomalies congénitales (AC) sont présentes chez environ 3 % des nouveau-nés et sont la cause d'environ 12 % des hospitalisations en pédiatrie. Elles constituent donc un important problème de santé publique. La surveillance est particulièrement importante, car il faut pouvoir évaluer convenablement les mesures de prévention (comme l'enrichissement des aliments en acide folique) sans recourir à une série d'études spéciales. La surveillance des AC présente des lacunes au Canada, où seules l'Alberta et la Colombie-Britannique ont des systèmes établis à cet effet. La plupart des provinces ont des systèmes de surveillance périnatale, mais leurs données sur les AC sont incomplètes, et les interruptions de grossesse n'y sont pas enregistrées. Il en va de même pour le système de l'Agence de la santé publique du Canada. Un nouveau réseau, le Fetal Alert Network, a été proposé pour l'Ontario; c'est un début, mais pour en faire un système vraiment représentatif de la population ontarienne, il faudra trouver des sources de vérification supplémentaires.