Epidemiologic characteristics of amniotic band sequence with limb malformations without body wall defect: data from the Polish Registry of Congenital Malformations

Abstract Amniotic Band Sequence (ABS) is a rare disruptive condition, with a variable spectrum of congenital defects caused by fibrous bands emerging as a result of amniotic rupture in the first trimester of gestation. Several factors, such as young parental age, primigravidity, febrile maternal illness, and drug use in the first trimester, were postulated to have substantial influence on ABS prevalence rate. We aimed our study to determine the prevalence of ABS with limb defects, but no body wall affectation, in a Polish population. We also examined the influence of different parental, gestational and environmental factors on the ABS prevalence value, and assessed the rate of gestational complications associated with this disorder. Among 1 706 639 births surveilled between 1998 and 2005, 36 liveborn infants with ABS-L were reported to the Polish Registry of Congenital Malformations, giving a global prevalence for a Polish population of 1 per 47 619 livebirths. We found that young maternal age, young paternal age, and primigravidity significantly increase the risk of ABS-L, when their effect was analyzed independently. However, because of a close relationship of these variables, we analyzed their mutually adjusted effect using conditional logistic regression models, and found that young maternal age proved the strongest risk factor for ABS-L (p = 0.0508). The condition was also more prevalent in infants with low birthweight (OR = 5.71; p < 0.0001). Since gestational complications are often relevant to maternal age and birth order, we introduced an adjustment for these variables, and found that respiratory tract infections and vaginal bleeding/spotting convey approximately fourfold increased risk of ABS-L (OR = 3.72/p = 0.0058 and OR = 3.70/p = 0.0014 respectively)

Pachydermoperiostosis-critical analysis with report of five unusual cases

Abstract Pachydermoperiostosis (idiopathic hypertrophic arthropathy) {MIM 167100} is an uncommon disease characterized by unique phenotype (digital clubbing and pachydermia) and distinctive radiographic appearances (periostosis). Two families are reported that, in additional to the typical phenotype and radiographic characteristics of pachydermoperiostosis, show some rare and/or unusual, not yet reported, clinical findings. In the first family, distinctive features were severe progressive arthritis with villonodular involvement of the knees. The clinical course of the disease was much more severe than usually reported. The older brother was disabled at the age of 29 years. In the second family, the clinical history was exceptional, with unique early appearance of clinical signs. Pachydermoperiostosis is usually inherited as a dominant trait, but probable autosomal recessive inheritance has been reported. Also in the present families, autosomal recessive inheritance is likely, possibly explaining the severe clinical course of the disease. Differential diagnosis and the confusing nomenclature of pachydermoperiostosis are discussed

Clinical expression of Holt-Oram syndrome on the basis of own clinical experience considering prenatal diagnosis

Objectives: Holt-Oram syndrome manifests with defects of upper limbs, pectoral girdle and cardiovascular system. The aim of this paper was to present complex clinical picture of the syndrome and its variable expression on the example of the family diagnosed genetically on the neonatal ward, after proband’s prenatal examination. Maretial and methods: Nine family members were tested for TBX5 gene mutation. Results: Four of family members were diagnosed with Holt-Oram syndrome and five had correct genetic test results. The diagnosis allowed to identify a genetic risk family and enabled to provide them with genetic counselling. Conclusions: Diagnosis of Holt-Oram syndrome is possible as early as in prenatal period and it can be verified by genetic tests

Prevalence of vascular disruption anomalies and association with young maternal age: A EUROCAT study to compare the United Kingdom with other European countries

Background Younger mothers are at a greater risk of having a pregnancy with gastroschisis and the risk is higher in the United Kingdom than other European countries. Gastroschisis is thought to be a vascular disruption anomaly and the aim of this study was to analyze the prevalence of other possible vascular disruption anomalies to determine whether both the younger maternal age and the UK associations also occur with these anomalies. Methods All pregnancies with anomalies considered potentially due to vascular disruption from January 1, 2005 to December 31, 2017 from 26 European population-based congenital anomaly registries who were members of EUROCAT were analyzed. Multilevel models were used to allow for differences between registries when analyzing associations with maternal age, year of birth and whether the registry was in the United Kingdom. Results There were 5,220 cases with potential vascular disruption anomalies, excluding chromosomal and genetic conditions, with a prevalence of 8.85 per 10,000 births in the United Kingdom and 5.44 in the other European countries. The prevalence per 10,000 births of gastroschisis (4.45 vs. 1.56) and congenital constriction bands (0.83 vs. 0.42) was significantly higher in the United Kingdom, even after adjusting for maternal age. However, transverse limb reduction defects had a similar prevalence (2.16 vs. 2.14 per 10,000). The expected increased prevalence in younger mothers was observed for vascular disruption anomalies overall and for the individual anomalies: gastroschisis and congenital constriction bands. Conclusion Vascular disruption anomalies that had an increased risk for younger mothers (such as gastroschisis) had a higher maternal age standardized prevalence in the United Kingdom, while vascular disruption anomalies with weaker associations with younger mothers (such as transverse limb reduction defects) did not have an increased prevalence in the United Kingdom, which may indicate a different etiology for these anomalies.publishedVersio

Prevalence of vascular disruption anomalies and association with young maternal age: A EUROCAT study to compare the United Kingdom with other European countries

[Corrections added after online publication, 16 November 2022: The last name of Dr. Jennifer M. Broughan was incorrectly spelled in the initial publication. It has been corrected.]Background: Younger mothers are at a greater risk of having a pregnancy with gastroschisis and the risk is higher in the United Kingdom than other European countries. Gastroschisis is thought to be a vascular disruption anomaly and the aim of this study was to analyze the prevalence of other possible vascular disruption anomalies to determine whether both the younger maternal age and the UK associations also occur with these anomalies. Methods: All pregnancies with anomalies considered potentially due to vascular disruption from January 1, 2005 to December 31, 2017 from 26 European population-based congenital anomaly registries who were members of EUROCAT were analyzed. Multilevel models were used to allow for differences between registries when analyzing associations with maternal age, year of birth and whether the registry was in the United Kingdom. Results: There were 5,220 cases with potential vascular disruption anomalies, excluding chromosomal and genetic conditions, with a prevalence of 8.85 per 10,000 births in the United Kingdom and 5.44 in the other European countries. The prevalence per 10,000 births of gastroschisis (4.45 vs. 1.56) and congenital constriction bands (0.83 vs. 0.42) was significantly higher in the United Kingdom, even after adjusting for maternal age. However, transverse limb reduction defects had a similar prevalence (2.16 vs. 2.14 per 10,000). The expected increased prevalence in younger mothers was observed for vascular disruption anomalies overall and for the individual anomalies: gastroschisis and congenital constriction bands. Conclusion: Vascular disruption anomalies that had an increased risk for younger mothers (such as gastroschisis) had a higher maternal age standardized prevalence in the United Kingdom, while vascular disruption anomalies with weaker associations with younger mothers (such as transverse limb reduction defects) did not have an increased prevalence in the United Kingdom, which may indicate a different etiology for these anomalies.European Commissioninfo:eu-repo/semantics/publishedVersio

Frequency of 22q11.2 microdeletion in children with congenital heart defects in western poland

<p>Abstract</p> <p>Background</p> <p>The 22q11.2 microdeletion syndrome (22q11.2 deletion syndrome -22q11.2DS) refers to congenital abnormalities, including primarily heart defects and facial dysmorphy, thymic hypoplasia, cleft palate and hypocalcaemia. Microdeletion within chromosomal region 22q11.2 constitutes the molecular basis of this syndrome. The 22q11.2 microdeletion syndrome occurs in 1/4000 births. The aim of this study was to determine the frequency of 22q11.2 microdeletion in 87 children suffering from a congenital heart defect (conotruncal or non-conotruncal) coexisting with at least one additional 22q11.2DS feature and to carry out 22q11.2 microdeletion testing of the deleted children's parents. We also attempted to identify the most frequent heart defects in both groups and phenotypic traits of patients with microdeletion to determine selection criteria for at risk patients.</p> <p>Methods</p> <p>The analysis of microdeletions was conducted using fluorescence <it>in situ </it>hybridization (FISH) on metaphase chromosomes and interphase nuclei isolated from venous peripheral blood cultures. A molecular probe (Tuple) specific to the <it>HIRA (TUPLE1, DGCR1</it>) region at 22q11 was used for the hybridisation.</p> <p>Results</p> <p>Microdeletions of 22q11.2 region were detected in 13 children with a congenital heart defect (14.94% of the examined group). Microdeletion of 22q11.2 occurred in 20% and 11.54% of the conotruncal and non-conotruncal groups respectively. Tetralogy of Fallot was the most frequent heart defect in the first group of children with 22q11.2 microdeletion, while ventricular septal defect and atrial septal defect/ventricular septal defect were most frequent in the second group. The microdeletion was also detected in one of the parents of the deleted child (6.25%) without congenital heart defect, but with slight dysmorphism. In the remaining children, 22q11.2 microdeletion originated <it>de novo</it>.</p> <p>Conclusions</p> <p>Patients with 22q11.2DS exhibit wide spectrum of phenotypic characteristics, ranging from discreet to quite strong. The deletion was inherited by one child. Our study suggests that screening for 22q11.2 microdeletion should be performed in children with conotruncal and non-conotruncal heart defects and with at least one typical feature of 22q11.2DS as well as in the deleted children's parents.</p

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome

Background The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. Methods We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. Results We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10(-14)). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. Conclusions We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.)

Genetic and Environmental Risk Factors for Isolated Hemangiomas in Infants

The goal of this analysis is to identify risk factors for infantile hemangiomas (IH) to better delineate hemangioma predisposition. We analyzed live birth children with isolated cutaneous hemangioma that were reported to the Polish Registry of Congenital Malformations from across Poland between the years 1998 and 2016. Lower birthweight and gestational age were the most significant risk factors associated with IH. We also observed a trend for a higher risk of IH with a lower level of maternal and paternal education. Moreover, mothers with IH have a higher probability of having a child with IH compared to fathers. However, this association is only present when the child is female. Similarly, a higher risk of hemangioma in a female child is found among mothers having relatives of the first degree with IH, compared to fathers with a similar pedigree. Our results suggest the role of exogenous factors in the etiology of IH. The analysis of familial cases suggests a multifactorial model of inheritance. The study indicates that female gender is an important risk factor for the expression of familial IH. Potential interaction of genetic risk factors with exposure to female sex hormones may play a role in the development of IH

Geospatial clustering of gastroschisis in Poland: Data from the Polish Registry of Congenital Malformations (PRCM)

Objectives: The aims of this study were: to evaluate the prevalence of abdominal wall defects in the Polish population, to analyze temporal trends in the prevalence, to identify areas (clusters) of high risk of abdominal wall defects, and to characterize, with respect to epidemiology, children with abdominal wall defects and their mothers in the area defined as a cluster. Material and Methods: We used isolated congenital malformations (gastroschisis Q79.3 and omphalocele Q79.2 according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10, the extended version)) data reported to the Polish Registry of Congenital Malformations (PRCM) over the years 1998– 2008 based on the population of 2 362 502 live births. We analyzed 11 administrative regions of Poland with complete epidemiologic data. Results: Of 11 regions, 2 had a significantly higher standardized prevalence of isolated gastroschisis: Dolnośląskie (1.7/10 000 live births, p = 0.0052) and Śląskie (1.9/10 000 live births, p < 0.0001). Furthermore, within the region of Dolnośląskie, we defined a clear prevalence of the isolated gastroschisis cluster (p = 0.023). We comprehensively examined demographic and socio-economic risk factors for abdominal wall defects in this area, and we found that these factors failed to account for the cluster. Conclusions: We identified a distinct prevalence cluster for isolated gastroschisis, although a precise reason for the disease clustering in this region remains unknown. Cluster identification enables more focused research aimed at identification of specific factors with teratogenic effects

Spatial and temporal clustering of isolated cleft lip with or without cleft palate in Poland

<div><p><i>Background</i>: Geographic variation in the prevalence of isolated cleft lip with or without cleft palate may be due to exogenous environmental factors or genetic variation. In this study, we aim to evaluate the prevalence of isolated cleft lip with or without cleft palate in Polish urban and rural environments in order to identify geographic areas with high prevalence (defect clusters). <i>Methods</i>: We use all cases of congenital malformations reported to the Polish Registry of Congenital Malformations in the years 1998–2008 from the total population of 2,362,502 births. <i>Results</i>: We detect a strong signal of increased prevalence of isolated cleft lip with or without cleft palate in a single region of Poland, the Dolnośląskie voivodeship. Furthermore, we demonstrate a statistically significant prevalence differences between the urban and rural areas within this region. Through our comprehensive spatiotemporal analysis, we precisely define the cluster of the highest risk that comprises the eastern part of this voivodeship.</p></div