Genitourinary Tract Anomalies Research Articles

Novel minimally invasive abdominoplasty for selected cases of prune belly syndrome: Step-by-step technique description and clinical indications

BackgroundPrune belly syndrome (PBS) is characterized by the triad of abdominal flaccidity, bilateral undescended testicles and genitourinary tract anomalies. A variable spectrum of abdominal wall laxity is observed in PBS. We present the first case of a novel technique using a minimally invasive abdominoplasty to specifically address patients with localized abdominal wall weakness in PBS. Case presentationA two-years-old child with PBS presented with recurrent febrile urinary tract infections. Ultrasonography demonstrated a dysplastic right kidney associated with significant ipsilateral ureterohydronephrosis. Voiding urethrocystogram did not show vesicoureteral reflux and DMSA scan depicted a non-functioning right kidney. During laparoscopic right nephroureterectomy and first stage Fowler-Stephens bilateral orchiopexies, a significant right-sided lateral abdominal wall bulging was observed. A minimally invasive laparoscopic abdominoplasty was performed with a one-way running suture using an unabsorbable 2.0 prolene approximating the edges of the musculofascial defect. While undergoing the second-stage Fowler-Stephens orchiopexy, no bulging was observed. ConclusionA minimally invasive abdominoplasty to improve abdominal wall lateral bulging in PBS was feasible and presented good cosmetic result. We anticipate that this technique can be applied for children with PBS with primary lateral abdominal wall bulging, employing one or more suture lines depending on the fascial defect size.

Streamlined identification of clinically and functionally relevant genetic regulators of lower-tract urogenital development

Congenital anomalies of the lower genitourinary (LGU) tract are frequently comorbid due to genetically linked developmental pathways, and are among the most common yet most socially stigmatized congenital phenotypes. Genes involved in sexual differentiation are prime candidates for developmental anomalies of multiple LGU organs, but insufficient prospective screening tools have prevented the rapid identification of causative genes. Androgen signaling is among the most influential modulators of LGU development. The present study uses SpDamID technology in vivo to generate a comprehensive map of the pathways actively regulated by the androgen receptor (AR) in the genitalia in the presence of the p300 coactivator, identifying wingless/integrated (WNT) signaling as a highly enriched AR-regulated pathway in the genitalia. Transcription factor (TF) hits were then assayed for sexually dimorphic expression at two critical time points and also cross-referenced to a database of clinically relevant copy number variations to identify 252 TFs exhibiting copy variation in patients with LGU phenotypes. A subset of 54 TFs was identified for which LGU phenotypes are statistically overrepresented as a proportion of total observed phenotypes. The 252 TF hitlist was then subjected to a functional screen to identify hits whose silencing affects genital mesenchymal growth rates. Overlap of these datasets results in a refined list of 133 TFs of both functional and clinical relevance to LGU development, 31 of which are top priority candidates, including the well-documented renal progenitor regulator, Sall1. Loss of Sall1 was examined in vivo and confirmed to be a powerful regulator of LGU development.

Gene dosage changes in KCTD13 result in penile and testicular anomalies via diminished androgen receptor function.

Despite the high prevalence of hypospadias and cryptorchidism, the genetic basis for these conditions is only beginning to be understood. Using array-comparative-genomic-hybridization (aCGH), potassium-channel-tetramerization-domain-containing-13 (KCTD13) encoded at 16p11.2 was identified as a candidate gene involved in hypospadias, cryptorchidism and other genitourinary (GU) tract anomalies. Copy number variants (CNVs) at 16p11.2 are among the most common syndromic genomic variants identified to date. Many patients with CNVs at this locus exhibit GU and/or neurodevelopmental phenotypes. KCTD13 encodes a substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3-ubiquitin-protein-ligase complex (BCR (BTB-CUL3-RBX1) E3-ubiquitin-protein-ligase complex (B-cell receptor (BCR) [BTB (the BTB domain is a conserved motif involved in protein-protein interactions) Cullin3 complex RING protein Rbx1] E3-ubiqutin-protein-ligase complex), which has essential roles in the regulation of cellular cytoskeleton, migration, proliferation, and neurodevelopment; yet its role in GU development is unknown. The prevalence of KCTD13 CNVs in patients with GU anomalies (2.58%) is significantly elevated when compared with patients without GU anomalies or in the general population (0.10%). KCTD13 is robustly expressed in the developing GU tract. Loss of KCTD13 in cell lines results in significantly decreased levels of nuclear androgen receptor (AR), suggesting that loss of KCTD13 affects AR sub-cellular localization. Kctd13 haploinsufficiency and homozygous deletion in mice cause a significant increase in the incidence of cryptorchidism and micropenis. KCTD13-deficient mice exhibit testicular and penile abnormalities together with significantly reduced levels of nuclear AR and SOX9. In conclusion, gene-dosage changes of murine Kctd13 diminish nuclear AR sub-cellular localization, as well as decrease SOX9 expression levels which likely contribute in part to the abnormal GU tract development in Kctd13 mouse models and in patients with CNVs in KCTD13.

Trends in the treatment of undescended testes: a pediatric tertiary care center experience from Croatia

ObjectiveUndescended testes (UDT) is the most common anomaly of the male genitourinary tract. The guidelines suggest that orchidopexy in congenitally UDT should be performed between 6 months and 18 months...

An incidental presentation of Herlyn–Werner-Wunderlich syndrome with secondary infertility

Rationale: Herlyn-Werner-Wunderlich syndrome, also known as obstructed hemi-vagina with ipsilateral renal agenesis (OHVIRA) syndrome, is a rare congenital anomaly of the Müllerian and Wolffian ducts. It is often asymptomatic until puberty and is usually misdiagnosed as infertility. Patient concerns: A 39-year-old woman desirous of pregnancy was referred to our radiodiagnosis unit for imaging evaluation on account of secondary infertility. Diagnosis: Incidental discovery of uterine bicornis bicollis and blind-ending hemivagina was noted at hysterosalpingography. Interventions: This necessitated the search for other genitourinary tract anomalies, and ipsilateral renal agenesis was also discovered. Outcomes: A diagnosis of Herlyn-Werner-Wunderlich syndrome was made. Lessons: Magnetic resonance imaging (MRI) is considered the gold standard imaging modality for the assessment of uterine malformations. However, in resource-poor centers where MRI is unavailable, a heightened clinical suspicion with the combination of available imaging modalities is important and reliable in making an accurate diagnosis, hence, successful management.

EP073: Interstitial deletion of 3q21 in a child with multiple congenital anomalies; Expanding the phenotype

Interstitial deletions in the long arm of chromosome 3 although relatively rare, have been reported to be associated with several congenital anomalies and developmental delays. Around eleven individuals with interstitial deletion spanning the region 3q21 have been reported with overlapping phenotype, including craniofacial dysmorphism, global developmental delay, skeletal manifestations, hypotonia, ophthalmological abnormalities, brain anomalies (mainly agenesis of corpus callosum), genitourinary tract anomalies, failure to thrive and microcephaly.

Prevalence of Congenital Anomalies in the Northwest of Iran

Prevalence of Congenital Anomalies in the Northwest of Iran

Hydroureter

Hydroureter

Association Between Obesity and Lower Urinary Tract Symptoms Among Children and Adolescents: A Community-Based Study.

Introduction: Obesity is associated with lower urinary tract symptoms (LUTSs) and dysfunction in adults while its impact on children and adolescents remains unknown. This study aimed to explore the impact of obesity on LUTSs among children and adolescents through a large-scale community-based study.Methods: From July 2004 to April 2017, children and adolescents aged 5–15 years-old in Xin-Dian District, New Taipei City were invited to participate in our study. The exclusion criteria were a history of congenital genitourinary tract anomalies, neurological anomalies, or a presence of urinary tract infection. After providing informed consent the participant completed a questionnaire, which included their baseline characteristics and dysfunctional voiding symptom score (DVSS); a parent completed the questionnaire with the younger children. Urgency and daytime incontinence were defined as having positive statement for DVSS questions 7 and 1, respectively. Multivariate regression analysis was used to evaluate the predictors of urgency, daytime incontinence and enuresis. A p-value of <0.05 was considered statistically significant.Results: A total of 2,371 participants were enrolled in the study, and 1,599 were ultimately eligible for analysis. The prevalence of urgency, daytime incontinence, constipation, and enuresis were 37.6, 6.4, 26.1, and 7.7%, respectively. Multivariate analysis revealed that younger age (p = 0.01) and obesity (p = 0.04) were independent predictors for urgency. Younger age (p < 0.01) and constipation (p = 0.04) were independent predictors for daytime incontinence but obesity was not. Younger children were more likely to have nocturnal enuresis (95% CI = 0.77–0.88) and obesity did not have a significant impact on enuresis.Conclusion: Obesity was significantly associated with urgency but it was not significantly associated with daytime incontinence and enuresis in community dwelling children and adolescents.

A Practical Approach to Congenital Urogenital Anomalies in Female Pediatric Patients.

Congenital anomalies of the female reproductive tract are relatively common and can be both confusing to understand as well as challenging to diagnose and manage in a busy pediatric clinical practice. Here, we lay out some of the most common genitourinary tract anomalies in female pediatric patients. We highlight the key embryologic development, present case examples, and discuss appropriate testing, treatment, and counseling for patients and their families regarding congenital disorders of the vulva, vagina, uterus, ovaries, and associated pathology. The goal of this review is to demystify these conditions and provide a practical guide for the general pediatrician who is often at the frontline making the initial diagnosis and caring for these patients. [Pediatr Ann. 2020;49(4):e188-e195.].

Fetal structural anomalies diagnosed during the first, second and third trimesters of pregnancy using ultrasonography: a retrospective cohort study.

The prevalence of congenital abnormalities in general populations is approximately 3-5%. One of the most important applications of obstetric ultrasound is in detection of fetal structural defects. To assess fetal structural anomalies diagnosed using ultrasound in the three trimesters of pregnancy. Retrospective cohort study at the Mário Palmério University Hospital of the University of Uberaba (Universidade de Uberaba, UNIUBE), from March 2014 to December 2016. Ultrasound data at gestational weeks 11-13 + 6, 20-24 and 32-36 were recorded to identify fetal anomalies in each trimester and in the postnatal period. The primary outcome measurements were sensitivity, specificity, positive predictive value and negative predictive value for detection of fetal anomalies and their prevalence. The prevalence of anomalies detected using ultrasound was 2.95% in the prenatal period and 7.24% in the postnatal period. The fetal anomalies most frequently diagnosed using ultrasound in the three trimesters were genitourinary tract anomalies, with a prevalence of 27.8%. Cardiac anomalies were diagnosed more often in the postnatal period, accounting for 51.0% of all cases. High specificity, negative predictive value and accuracy of ultrasound were observed in all three trimesters of pregnancy. Ultrasound is safe and has utility for detecting fetal anomalies that are associated with high rates of morbidity and mortality. However, the low sensitivity of ultrasound for detecting fetal anomalies in unselected populations limits its utility for providing reassurance to examiners and to pregnant women with normal results.

Challenging diagnosis of prune belly syndrome antenatally: a case report

BackgroundPrune belly syndrome is a rare congenital condition of uncertain etiology.It is characterized with a triad of abdominal distension due to deficient abdominal wall, genitourinary tract anomalies, and musculoskeletal anomalies. This condition varies in its severity which makes diagnosis challenging during early antenatal scanning.Case presentationWe reported a severe phenotype of prune belly syndrome which was not fully suspected in a 29-year-old Saudi woman was G4T2P0A1L2 at 21 weeks of gestation at the time of early antenatal presentation; however, it became apparent during diagnosis at a subsequent follow-up scan during advanced gestational age.ConclusionWe conclude that suspicion of such anomalies through an early antenatal scan require an urgent further follow-up scan in a tertiary center. The referral to the tertiary center must be to an experienced ultrasonographer and maternal–fetal medicine specialist for a decision to be made antenatally regarding the course of pregnancy and post-delivery management based on the severity of the condition.

Tubo-Ovarian Abscesses in Nonsexually Active Adolescent Females: A Large Case Series

PurposeThe aim of the study was to review the incidence, presentation, and management of tubo-ovarian abscesses (TOA) in nonsexually active (NSA) adolescents. MethodsA retrospective chart review was performed at a single children's hospital. We evaluated self-reported NSA females aged < 21 years diagnosed with TOA. Demographics, presenting symptoms, medical history, laboratory studies, imaging, and treatment were reviewed. ResultsSixteen NSA females met inclusion criteria, with one patient presenting with two separate TOAs. Mean age at diagnosis was 14.6 ± 1.8 years; all were menarchal. Presenting symptoms included abdominal pain (88%), fever (76%), and vomiting (53%). Eleven patients (65%) received transabdominal pelvic ultrasound, 2 (12%) had magnetic resonance imaging of pelvis, and 11 (65%) had computed tomography of abdomen/pelvis. All patients had negative gonorrhea and chlamydia testing. Thirteen (76%) had comorbid disease including obstructed hemivagina ipsilateral renal agenesis, active or recent appendicitis, or genitourinary tract anomalies. Sixteen cases underwent drainage via interventional radiology or surgery. Twelve cases (71%) had TOA fluid cultured; five (29%) grew Escherichia coli species. All cases received intravenous antibiotics, and 88% of cases continued outpatient oral antibiotics. ConclusionsAlthough uncommon in NSA females, patients with underlying comorbidities may be at increased risk for TOA formation. Providers should consider the diagnosis of TOA even in NSA females.

Clinical Study of 31 Polydactyly Cases Admitted to Neonatal Intensive Care Unit

Objective: To investigate polydactyly in neonates who were admitted to neonatal intensive care unit (NICU) due to urgent medical needs. Methods: Retrospective chart review of polydactyly neonates admitted to NICU of Chungnam National University Hospital between September 1997 and September 2018 was carried out. Patient data, type of polydactyly accompanying anomalies, genetic testing and clinical follow-up after discharge were reviewed and analyzed. Results: Thirty-one neonates with polydactyly were admitted to NICU during the selected period. 61.3% were male. Most were admitted for the evaluation and treatment for other congenital anomalies. Ten neonates (32%) were small for gestational age. The most frequently observed forms of polydactyly were preaxial hand polydactyly and postaxial foot polydactyly. Cardiac anomalies (35%) were more frequent in the population than genitourinary tract anomalies (22%), central nervous system anomalies (22%), gastrointestinal tract anomalies (19%) and congenital hypothyroidism. Four neonates showed abnormal genetic finding. Three neonates were diagnosed syndromic disorder after discharge (CATCH22 syndrome, VACTERL association, Joubert syndrome). Pregnancy of these neonates was complicated by maternal diabetes (13%), hepatitis B virus (6%), exposure to herbal medicine or smoking (6%), pre-eclampsia and hypertension. Only one case in the study had positive family history for polydactyly. Conclusion: Polydactyly could serve as a clue to syndromes and genetic disorders if associated with multiple major organ anomalies.

Practice patterns in ordering a voiding cystourethrogram for pediatric patients among different specialties in a Middle Eastern tertiary care center.

Introduction:Voiding cystourethrogram (VCUG) is a very popular test performed to evaluate genitourinary tract anomalies. Nevertheless, this test can be overused and can lead to unnecessary patient discomfort, radiation exposure, and cost. We sought to study the practice patterns in ordering a VCUG in a Middle Eastern tertiary care center.Methods:Over a period of 3 years, a retrospective analysis of all VCUG images done for pediatric patients in a single center was made. Further clinical details were extracted from the electronic health records. The specialty of an ordering physician and the reported indication for the procedure were noted. Indications for VCUG were recorded based on the AAP 2011 guidelines, NICE guidelines 2007, and ACR 2011 guidelines. Based on these criteria, patients were analyzed.Results:A total of 92 VCUGs were evaluated. Of all VCUGs done, pediatricians ordered the most VCUGs (50/92), followed by pediatric infectious disease (16/92), pediatric nephrology (9/92), pediatric urology (7/92), adult urology (5/92), pediatric surgery (3/92), obstetrician-gynecologist (1/92), and emergency medicine (1/92). Properly indicated VCUGs were 50% by general pediatrics, 55% by pediatric infectious disease, 45% by pediatric nephrology, 40% by adult urology, 33% by pediatric surgery, and 100% by pediatric urology.Conclusion:VCUG is utilized differently by different specialties. In some centers, adult specialties may order a pediatric VCUG. General pediatricians order VCUG the most with a tendency for misuse in up to 50%. Pediatric urology is not the most ordering specialty of VCUG; however, it utilizes it most appropriately. The noted practice patterns may be improved with awareness of the indications and limitations of the study and with proper referral.

Anomalies of the genitourinary tract in children with 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome (22q11.2DS) involves multiple organ systems with variable phenotypic expression. Genitourinary tract abnormalities have been noted to be present in up to 30-40% of patients. At our institution, an internationally recognized, comprehensive, and multidisciplinary 22q11.2DS care center has been providing care to these children. We sought to report on the incidence of genitourinary tract anomalies in this large cohort and, therefore, retrospectively reviewed all patients who underwent a complete evaluation from 1992 to March 2017. We identified all children with any genital or urinary tract anomaly. For all children with a diagnosis of hydronephrosis, the underlying etiology was determined, when possible. Overall, 1,073 of 1,267 children with 22q11.2DS underwent renal evaluations at our institution. Hundered Sixty-Two (15.1%) children had structural abnormalities of their kidneys/urinary tracts. The majority of children with hydronephrosis (63%) had isolated upper tract dilation without any additional diagnoses. Boys were significantly more likely to be diagnosed with a genital abnormality than girls (7.7 vs. 0.5%, p < 0.001). Of the 649 boys in the entire cohort, 24 (3.7%) had cryptorchidism and 24 (3.7%) had hypospadias, which was noted to be mild in all except one boy. Overall, findings of hydronephrosis, unilateral renal agenesis, and multicystic dysplastic kidney occur at higher rates than expected in the general population. Given these findings, in addition to routine physical examination, we believe that all patients with 22q11.2DS warrant screening RBUS at time of diagnosis.

Anatomical associations and radiological characteristics of Scimitar syndrome on CT and MR

PurposeTo report the anatomical associations and radiological characteristics of Scimitar syndrome on CT and MR. Materials and methodsRetrospective review of the medical records between February 2001 and February 2016 was performed. To identify patients, radiological reports were queried for “Scimitar” or “partial anomalous pulmonary venous return.” Patients with radiological findings of Scimitar syndrome were included. Patients without cross-sectional imaging were excluded. Patients' demographics, radiologic images, and medical notes were reviewed. Two radiologists re-read the available imaging studies. Images were reviewed for Scimitar syndrome confirmation, number and location of Scimitar vein drainage, number of lobes drained by the Scimitar vein, and right pulmonary artery and lung hypoplasia. In addition, the number of pulmonary veins draining into the left atrium, left sided anomalous pulmonary veins, congenital heart disease, aortic arch anomalies, cardiac dextroposition, right ventricular enlargement, pulmonary artery enlargement, and elevated QP:QS ratios were identified. Other associated anomalies including the presence of an anomalous feeding artery and pulmonary sequestration, abnormal lobar pattern, localized bronchiectasis, horseshoe lung, accessory diaphragm, diaphragmatic hernia, vertebral anomalies, and genitourinary tract anomalies were reviewed. ResultsSixteen patients (3 males, 13 females; mean age 39.5 years, range 14 days–72 years) with confirmed Scimitar syndrome on CT and MR imaging were identified. The Scimitar vein drained to the infra-diaphragmatic inferior vena cava (IVC) in ten patients and to the supra-diaphragmatic IVC in six patients. The most common associated anomalies were right ventricle enlargement (93.3%), variant lobar pattern of the right lung (92.9%), enlarged pulmonary arteries (60%), and cardiac dextroposition (50%). ConclusionRecognizing the radiologic characteristics and anatomical associations of Scimitar syndrome is important as features of the primary condition and associated anomalies may have implications in surgical management.

The efficacy of extracorporeal shockwave lithotripsy for symptomatic ureteral stones: Predictors of treatment failure without the assistance of computed tomography.

ObjectivesNon-contrast computed tomography (NCCT) is not always performed clinically if the diagnosis of ureteral calculi has been confirmed using other radiographic imaging modalities. The aim of this study was to identify predictors of successful extracorporeal shockwave lithotripsy (ESWL) without assistance of NCCT.MethodsWe retrospectively reviewed the medical records of patients with symptomatic solitary ureteral stones who underwent ESWL between November 2015 and January 2016. Abdominal plain radiography or intravenous urography were performed before ESWL for localization. The exclusion criteria were repeated sessions of ESWL for the target stone and congenital genitourinary tract anomalies. The demographic characteristics, clinical history, medical charges, or imaging features of the stones were recorded. Successful treatment was defined as no fragments detected on radiography or ultrasonography in 4 weeks. For radiolucent calculi, successful treatment was regarded as cases without hydronephrosis, symptoms, or hematuria. Patients experiencing intractable pain and undergoing subsequent auxiliary surgeries were regarded as having ESWL treatment failure.ResultsAge (odds ratio [OR], 1.042; 95% confidence interval [CI], 1.007–1.078), history of ipsilateral renal or ureteral calculi episodes (OR, 2.669; 95% CI, 1.281–5.687), stone burden (OR, 3.499; 95% CI, 1.284–9.530), and radiopaque stone (OR, 2.351; 95% CI, 1.049–5.267) were significant predictors of ESWL failure in all patients.ConclusionsFor treating symptomatic ureteral stones, those with smaller size, radiolucency, and without a history of ipsilateral renal or ureteral calculi could be considered for first-line therapy with ESWL.

Association of structural and numerical anomalies of chromosome 22 in a patient with syndromic intellectual disability

Array comparative genomic hybridization (aCGH) is now widely adopted as a first-tier clinical diagnostic test for patients with developmental delay (DD)/intellectual disability (ID), autism spectrum disorders, and multiple congenital anomalies. Nevertheless, classic karyotyping still has its impact in diagnosing genetic diseases, particularly mosaic cases.We report on a 30 year old patient with syndromic intellectual disability, a 22q13.2 microdeletion and mosaic trisomy 22. The patient had the following clinical features: intrauterine growth retardation at birth, hypotonia, cryptorchidism, facial asymmetry, enophthalmus, mild prognathism, bifid uvula, hypoplastic upper limb phalanges, DD including speech delay, and ID. Whole genome aCGH showed a de novo 1 Mb interstitial heterozygous deletion in 22q13.2, confirmed by fluorescence in situ hybridization in all cells examined. Moreover, 18% cells had an extra chromosome 22 suggesting a trisomy 22 mosaicism.Almost all 22q13 deletions published so far have been terminal deletions with variable sizes (100 kb to over 9 Mb). Very few cases of interstitial 22q13.2 deletions were reported. In its mosaic form, trisomy 22 is compatible with life, and there are about 20 reports in the literature. It has a variable clinical presentation: growth restriction, dysmorphic features, cardiovascular abnormalities, hemihyperplasia, genitourinary tract anomalies and ID. Neurodevelopmental outcome ranges from normal to severe DD. The patient presents clinical features that are common to both the interstitial 22q13 deletion and the mosaic trisomy 22; characteristics related to the interstitial deletion alone and others explained solely by the mosaic trisomy.Our case points out the role of conventional cytogenetic tools in mosaic cases that could be missed by microarray technology. We therefore suggest the combination of both conventional and molecular karyotyping in the investigation of certain genetic diseases.

Exploring the genetic basis of 3MC syndrome: Findings in 12 further families.

The 3MC syndromes are a group of rare autosomal recessive disorders where the main clinical features are cleft lip and palate, hypertelorism, highly arched eyebrows, caudal appendage, postnatal growth deficiency, and genitourinary tract anomalies. Ophthalmological abnormalities, most notably anterior chamber defects may also be seen. We describe the clinical and molecular findings in 13 individuals with suspected 3MC syndrome from 12 previously unreported families. The exclusion of the MASP1 and COLEC11 Loci in two individuals from different consanguineous families and the absence of mutations in four further individuals sequenced for both genes raises the possibility that that there is further genetic heterogeneity of 3MC syndrome.