Search Results (11)

Background/Objectives: To identify distinct sonographic phenotypes of complex malformations of the fetal ventral wall. Methods: We performed a retrospective analysis of ultrasound reports from 160 fetuses diagnosed with complex ventral wall defects at a single tertiary referral center between 1997 and 2021. Agglomerative hierarchical clustering was applied to identify distinct sonographic phenotypes based on the level of the ventral wall defect and associated anomalies. Results: Ventral wall defects involved the abdominal wall in 150 cases, the thoracic wall in 42 cases, and the pelvic wall in 28 cases, either in isolation or in combination. Open neural tube defects were present in 58 fetuses (36.3%), spinal defects in 110 fetuses (68.8%), and limb anomalies in 45 fetuses (28.1%). Additional anomalies were identified in 38 fetuses (23.8%), including cardiac anomalies in 18 cases (11.3%). Amniotic bands were observed in seven cases (4.4%). Using agglomerative hierarchical clustering, five groups of fetuses with differing numbers of observations were identified (cluster 1, n = 104; cluster 2, n = 5; cluster 3, n = 30; cluster 4, n = 10; cluster 5, n = 11). The silhouette score of the clustering model was 0.3285. The most discriminative features for each cluster, expressed as feature importance values, were as follows: kyphoscoliosis for cluster 1 (0.924), pelvic wall defect for cluster 2 (0.852), ectopia cordis for cluster 3 (0.662), limb anomalies for cluster 4 (0.767), and spina bifida for cluster 5 (0.691). Conclusions: Complex malformations of the fetal ventral wall are associated with a wide spectrum of additional anomalies. Hierarchical clustering identified five distinct sonographic phenotypes of complex ventral wall defects, highlighting the heterogeneity of these conditions. Full article

Congenital anomalies of the kidney and urinary tract (CAKUT) represent a broad range of diseases with differing mechanisms, clinical presentations, and prognoses. With an estimated prevalence of between 4 and 60 per 10,000 births, CAKUT represents a sizable number of patients for pediatric and adult nephrologists as therapies have progressed, allowing longer life spans. Many CAKUT disorders are associated with genetic mutations, and with advances in genomic sequencing, these genes are being identified at an increasing rate. Understanding these mutations provides insight into these conditions’ molecular mechanisms and pathophysiology. In this article, we discuss the epidemiology, presentation, and outcomes of CAKUT in addition to our current understanding of genetic and molecular mechanisms in these diseases. Full article

Cloacal exstrophy is the most severe congenital anomaly of the exstrophy–epispadias complex and is characterized by gastrointestinal, genitourinary, neurospinal, and musculoskeletal malformations. Individualized surgical reconstruction by a multidisciplinary team is required for these complex patients. Not infrequently, patients need staged surgical procedures throughout childhood and adolescence. Following significant improvements in medical care and surgical reconstructive techniques, nearly all patients with cloacal exstrophy now survive, leading to an increased emphasis on quality of life. Increased attention is given to gender identity and the implications of reconstructive decisions. Long-term sequelae of cloacal exstrophy, including functional continence and sexual dysfunction, are recognized, and many patients require ongoing complex care into adulthood. Full article

Background: The bladder exstrophy-epispadias complex (BEEC) is a spectrum of congenital abnormalities that involves the abdominal wall, the bony pelvis, the urinary tract, the external genitalia, and, in severe cases, the gastrointestinal tract as well. Methods: Herein, we performed an exome analysis of case-parent trios with cloacal exstrophy (CE), the most severe form of the BEEC. Furthermore, we surveyed the exome of a sib-pair presenting with classic bladder exstrophy (CBE) and epispadias (E) only. Moreover, we performed large-scale re-sequencing of CBE individuals for novel candidate genes that were derived from the current exome analysis, as well as for previously reported candidate genes within the CBE phenocritical region, 22q11.2. Results: The exome survey in the CE case-parent trios identified two candidate genes harboring de novo variants (NR1H2, GKAP1), four candidate genes with autosomal-recessive biallelic variants (AKR1B10, CLSTN3, NDST4, PLEKHB1) and one candidate gene with suggestive uniparental disomy (SVEP1). However, re-sequencing did not identify any additional variant carriers in these candidate genes. Analysis of the affected sib-pair revealed no candidate gene. Re-sequencing of the genes within the 22q11.2 CBE phenocritical region identified two highly conserved frameshift variants that led to early termination in two independent CBE males, in LZTR1 (c.978_985del, p.Ser327fster6) and in SLC7A4 (c.1087delC, p.Arg363fster68). Conclusions: According to previous studies, our study further implicates LZTR1 in CBE formation. Exome analysis-derived candidate genes from CE individuals may not represent a frequent indicator for other BEEC phenotypes and warrant molecular analysis before their involvement in disease formation can be assumed. Full article

Introduction. Recent reports linking prenatal and community cannabis exposure to elevated uronephrological congenital anomaly (UCA) rates (UCAR’s) raise the question of its European epidemiology given recent increases in community cannabinoid penetration there. Methods. UCAR data from Eurocat. Drug use data from European Monitoring Centre for Drugs and Drug Addiction. Income from World bank. Results. UCAR increased across Spain, Netherlands, Poland and France. UCAR’s and cannabis resin THC increased simultaneously in France, Spain, Netherlands and Bulgaria. At bivariate analysis all UCA’s were related to cannabis herb and resin THC concentrations. All UCAR’s were bivariately related to cannabis metrics ordered by median minimum E-value (mEV) as hypospadias > multicystic renal disease > bilateral renal agenesis > UCA’s > hydronephrosis > posterior urethral valve > bladder exstrophy/epispadias. At inverse probability weighted multivariable analysis terms including cannabis were significant for the following series of anomalies: UCA’s, multicystic renal disease, bilateral renal agenesis, hydronephrosis, congenital posterior urethral valves from P = 1.91 × 10⁻⁵, 2.61 × 10⁻⁸, 4.60 × 10⁻¹⁵, 4.60 × 10⁻¹⁵ and 2.66 × 10⁻¹⁰. At geospatial analysis the same series of UCA’s were significantly related to cannabis from P = 7.84 × 10⁻¹⁵, 7.72 × 10⁻⁵, 0.0023, 6.95 × 10⁻⁵, and 8.82 × 10⁻⁵. 45/51 (88.2%) of E-value estimates and 31/51 (60.8%) of mEV’s >9. Conclusion. Analysis confirms a close relationship between cannabis metrics and all seven UCA’s and fulfill formal criteria for quantitative causal inference. Given the exponential cannabinoid genotoxicity dose–response relationship results provide a powerful stimulus to constrain community cannabinoid exposure including protection of the food chain to preserve the genome and epigenome of coming generations. Full article

In the case of pediatric urology there are several congenital conditions, such as hypospadias and neurogenic bladder, which affect, respectively, the urethra and the urinary bladder. In fact, the gold standard consists of a urethroplasty procedure in the case of urethral malformations and enterocystoplasty in the case of urinary bladder disorders. However, both surgical procedures are associated with severe complications, such as fistulas, urethral strictures, and dehiscence of the repair or recurrence of chordee in the case of urethroplasty, and metabolic disturbances, stone formation, urine leakage, and chronic infections in the case of enterocystoplasty. With the aim of overcoming the issue related to the lack of sufficient and appropriate autologous tissue, increasing attention has been focused on tissue engineering. In this review, both the urethral and the urinary bladder reconstruction strategies were summarized, focusing on pediatric applications and evaluating all the biomaterials tested in both animal models and patients. Particular attention was paid to the capability for tissue regeneration in dependence on the eventual presence of seeded cell and growth factor combinations in several types of scaffolds. Moreover, the main critical features needed for urinary tissue engineering have been highlighted and specifically focused on for pediatric application. Full article

Objective: The aim of this study was to evaluate the outcomes of single-stage trans-vestibular and Foley’s assisted epispadias repair (STAFER) technique in girls with incontinent epispadias. Methods: The records of all girls who had undergone epispadias repair and bladder neck plication via the STAFER technique over a four-year study period (January 2016 to December 2019) were retrospectively reviewed from the archives. A comparison of preoperative and postoperative functional outcomes was performed. Incontinence status was divided into four grades on the basis of severity: grade 0 (completely dry during day and night), grade 1 (occasional episodes of urine leakage leading to damp undergarments or requiring pads occasionally but not daily), grade 2 (frequent episodes of urine leakage with a dry period of <3 h), and grade 3 (completely incontinent). Renal bladder ultrasound (RBUS), micturating cystourethrogram (MCUG) scan, technetium-99m diethylenetriamine pentaacetate (DTPA) scan, and technetium-99m dimercaptosuccinic acid (DMSA) scan were performed to assess the upper tract function. Results: Nine girls with average (SD) age at surgery of 7.9 (3.8) years were operated on utilizing the STAFER technique during the study period. All cases had grade 3 incontinence and normal upper tracts prior to the surgery. Postoperatively, 8/9 girls had a dry period of more than 3 h. Six of them were completely dry and had no wetting episodes (grade 0 incontinence). DMSA and DTPA scans showed preserved upper tracts while MCUG scans revealed grade II VUR in only one case. Conclusions: In a limited cohort of girls with incontinent epispadias, the STAFER technique provides favorable functional outcomes in terms of continence and upper tract function. Further studies comprising a larger cohort of patients with a younger average age at surgery need to be conducted before definite conclusions regarding the efficacy of this technique are drawn. Full article

The bladder exstrophy–epispadias complex (BEEC) is an abdominal midline malformation comprising a spectrum of congenital genitourinary abnormalities of the abdominal wall, pelvis, urinary tract, genitalia, anus, and spine. The vast majority of BEEC cases are classified as non-syndromic and the etiology of this malformation is still unknown. This review presents the current knowledge on this multifactorial disorder, including phenotypic and anatomical characterization, epidemiology, proposed developmental mechanisms, existing animal models, and implicated genetic and environmental components. Full article

The term exstrophy-epispadias complex refers to a group of midline defects ranging from epispadias to cloacal exstrophy. Bladder exstrophy is the most frequent malformation of this spectrum and it can present as a classical or a variant form. We report a case of a hybrid bladder exstrophy variant having some characteristics of both a duplicate bladder exstrophy and a superior vesical fistula. Full article

Introduction: To report our experience in continent urinary diversions, we describe two cases we treated performing detubularized ureterosigmoidostomy. In children, in the case of malformations or neoplastic diseases affecting the bladder, the need for a cystectomy is not so frequent. When cystectomy becomes mandatory, there is a need to create a continent bladder diversion. Mainz pouch II and Cologne pouch are procedures that utilize a detubularized sigma as a reservoir in order to build up a continent neo-bladder. Materials and methods: This is a retrospective study performed at the Pediatric Surgical Unit of the Salesi Children’s Hospital. In this work, we reviewed data about two patients who underwent surgery for the creation of a sigmoid neo-bladder by the Mainz pouch II and Cologne pouch techniques. Results: In our experience, we treated a girl who was affected by a bladder’s rabdomiosarcoma and a girl born with a bladder exstrophy and treated at birth abroad. In both patients, a complete cystectomy was performed and a continent neo-bladder was created by a detubularized ureterosigmoidostomy. In the first case, we performed the Mainz pouch II technique and in the second, the Cologne pouch technique. Discussion: Different techniques have been developed with the main goal of the creation of an orthotopic neo-bladder, which has to be a low pressure reservoir with a continent sphincteric mechanism. Detubularized ureterosigmoidostomy is a good choice in pediatric patients. Our study, according to other works, shows that these procedure are safe with good long-term outcomes. Full article

Genetic factors play a critical role in the development of human diseases. Recently, several molecular genetic studies have provided multiple lines of evidence for a critical role of genetic factors in the expression of human bladder exstrophy-epispadias complex (BEEC). At this point, ISL1 (ISL LIM homeobox 1) has emerged as the major susceptibility gene for classic bladder exstrophy (CBE), in a multifactorial disease model. Here, GWAS (Genome wide association studies) discovery and replication studies, as well as the re-sequencing of ISL1, identified sequence variants (rs9291768, rs6874700, c.137C > G (p.Ala46Gly)) associated with CBE. Here, we aimed to determine the molecular and functional consequences of these sequence variants and estimate the dependence of ISL1 protein on other predicted candidates. We used: (i) computational analysis of conserved sequence motifs to perform an evolutionary conservation analysis, based on a Bayesian algorithm, and (ii) computational 3D structural modeling. Furthermore, we looked into long non-coding RNAs (lncRNAs) residing within the ISL1 region, aiming to predict their targets. Our analysis suggests that the ISL1 protein specific N-terminal LIM domain (which harbors the variant c.137C > G), limits its transcriptional ability, and might interfere with ISL1-estrogen receptor α interactions. In conclusion, our analysis provides further useful insights about the ISL1 gene, which is involved in the formation of the BEEC, and in the development of the urinary bladder. Full article