Congenital Urogenital Abnormalities Research Articles

Relationship Between Vesicoureteric Reflux and Nephrocalcinosis in Children: A Case-Control Study at a Tertiary Medical Center in Saudi Arabia.

Vesicoureteral reflux (VUR), one of the most common pediatric congenital urogenital abnormalities, refers to the abnormal backflow of urine from the urinary bladder back into the ureter or to the kidney. This causes urinary tract infections. Nephrocalcinosis (NC) refers to abnormal deposits of calcium within the renal parenchyma and/or in the renal cortex.Patients with NC are mostly asymptomatic and severe disease may progress to renal failure. Early diagnosis through examinationssuchas radiography, computed tomography, and ultrasonography, is crucial for therapeutic treatment. Ultrasonography is the preferred method for scanning and grading nephrocalcinosis in children, primarily because it emits no radiation. This study aimed to increase the body of knowledge regarding VUR and nephrocalcinosis by determining its prevalence and assessingthe relationship between VUR and nephrocalcinosis in children presenting at our institution. ​​​​Methods:A case-control study was conducted using data from the medical records of 632 children younger than 14 years in a tertiary medical center in Riyadh, Saudi Arabia. Eligible participants were assigned to two groups: Group 1 consisted of 316 patients with VUR, while Group 2 consisted of 316 sex- and age-matched patients without VUR. The difference in the prevalence of nephrocalcinosis between the two groups was assessed. Frequency and percentage were used to present the categorical variables; Pearson product-moment correlation was utilized to establish the association between VUR and nephrocalcinosis. Statistical significance was established at p<0.05. ​​​​​Result:Only two cases in Group 1 were positive for nephrocalcinosis (0.63%, one male and one female), while four cases in Group 2 were positive for the condition (1.26%, two males and two females). There was no significant difference in the incidence of nephrocalcinosis between the two groups (p=0.873), indicating no relationship between VUR and nephrocalcinosis in children. There is no relationship between VUR and nephrocalcinosis in children under the age of 14 years.

Congenital Urethrovaginal Fistula with Blind-Ending Vagina in a Female Pseudohermaphrodite Dog with Urinary Incontinence

An 8 mo old male Doberman pinscher was referred for investigation of persistent urinary incontinence. Physical examination revealed urine leakage and abnormal external genitalia. A computed tomography scan identified a large fluid-filled cavity extending from the caudoventral abdomen displacing the colon and urinary bladder. No retained testicles were identified. A retrograde urethrogram study found a linear communication, cranial to the pubic brim between the urethra to the fluid-filled cavity (fistula). Exploratory celiotomy was performed, and an entire female reproductive tract with a blind-ending vagina and a urethrovaginal fistula was found. En bloc gonad hysterectomy was performed, the fistula was transected, and a careful urethral reconstruction was performed. The urinary incontinence resolved immediately after surgery, and no complications were reported. Mild urinary incontinence recurred 4 days following patient discharge, and a urine bacterial culture was positive for Klebsiella spp. An antibiotic course was prescribed, and the incontinence fully resolved. Congenital urogenital abnormalities should always be considered in young animals presenting with urinary incontinence. Here, a young female pseudohermaphrodite dog with a naturally occurring congenital urethrovaginal fistula is described. Exploratory surgery was required for definitive diagnosis and surgical intervention yielded a good medium-term outcome with resolution of clinical signs.

The Clinical Severity of Alpha-2 Globin Gene Variants: Homozygosity for Hb Agrinio (HBA2: c.89T>C) Leads to Severe Antenatal Anemia, about 8 Cases in 3 Families

Introduction: Hemoglobin (Hb) Agrinio (HBA2: c.89T&amp;gt;C (Leu29Pro) mutation) is a rare highly unstable Hb variant resulting from a leucine to proline substitution at codon29 of the alpha2-globin gene. Eleven homozygous cases of this non-deletional alpha thalassemia were described in literature. Clinical course ranged from moderate (non-transfusion dependent anemia) to severe (transfusion dependent thalassemia). In addition, one probable case of Hb barts hydrops fetalis was also reported in a Greek series. Hb Agrinio was first described in individuals of Greek or Cypriot origins. Subsequently, some cases were reported among patients living in Spain and Macedonia, most often of Gypsy origin. We report here the clinical presentation of the 8 homozygous cases diagnosed by molecular biology analysis in France and underline the severity of the antenatal phenotype of the disease. Methods: Cases were identified by contacting all the French laboratories involved in the molecular diagnosis of hereditary red blood cell (RBC) disorders. Three different families were retrieved, including 8 pediatric homozygous cases diagnosed by alpha globin gene sequencing between 2006 and 2020. Standardized clinical and laboratory data were obtained from treatment centers. All parents gave their written consent for molecular analysis and their authorization for participating in this study. Results: Consanguinity was present in all 3 families, however no obvious link was found between the 3. Two originated from Spain (1 of gypsy origin) and 1 from Bulgaria. All patients were homozygous for the HBA2: c.89T&amp;gt;C mutation, without any additional beta or alpha anomalies using gene sequencing and MLPA. Main clinical presentation findings of homozygous patients are reported in the table. Among the 8 cases, there was one in utero death at 22 weeks GA and 7 living births. Three patients, the more anemic at birth, died during the first hours of life with a clinical picture of hydrops fetalis for 2 of them. Despite a normal cerebral doppler at 32 weeks of GA, the third newborn (II2), presented at birth with a blueberry syndrome with cutaneous and hepatic extramedullary hematopoiesis, severe pulmonary arterial hypertension and Hb value of 6 g/dl, leading to neonatal death. Among the 4 survivor patients, one (III3), diagnosed in the antenatal period, benefited from in utero transfusions (TF) administered at 23 and 27 weeks because an accelerated middle cerebral artery peak systolic velocity of 52cm/s was measured. Hypospadias with ambiguous genitalia requiring surgical treatment was present in one patient and micropenis treated medically and undescended testis in a second one. All survivors (n=4/8) are currently under regular TF and chelation therapy. TF were generally (3/4) occasional in the first years of life and then became regular (&amp;gt;8 TF/year) later in childhood (at 6, 6, 7 years of age respectively). Conclusions: our national experience of homozygous Hb Agrinio cases revealed a more severe clinical course than reported in literature, with clinical presentation ranging from alpha-thalassemia major (Hb Barts hydrops fetalis) to severe non deletional HbH disease. Antenatal anemia was profound. In utero or neonatal deaths concerned half of the patients and additional ones were, even not biologically confirmed, also found in the family histories. Of note, congenital urogenital abnormalities similar to those found in the classical Hb Bart's Hydrops FetalisSyndrome were found in 2 patients. This up to now unreported severity could be explained by a closer monitoring and a more comprehensive clinical study of the cases/siblings allowing the antenatal period to be better described. The existence of aggravating genetic factor is another hypothesis and NGS analysis of genes involved in RBC disorders is planned. In couples at risk for homozygous Hb Agrinio, early genetic counseling and prenatal diagnosis should be offered. If the pregnancy is continued, a very close fetal ultrasound monitoring is mandatory and intrauterine TFs can be administered when severe fetal anemia is detected. Table Disclosures Thuret: Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Investigator in clinical trials; Novartis pharma: Membership on an entity's Board of Directors or advisory committees, Other: Investigator in clinical trials; bluebird bio, Inc.: Membership on an entity's Board of Directors or advisory committees, Other: Investigator in clinical trials; Apopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Congenital urogenital abnormalities in children with congenital hypothyroidism.

Background: Congenital hypothyroidism (CH), as one of the most common congenital endocrine disorders, may be significantly associated with congenital malformations. This study investigates urogenital abnormalities in children with primary CH (PCH). Methods: This case-control study was conducted on 200 children aged three months to 1 year, referred to Amir-Kabir Hospital, Arak, Iran. One hundred children with PCH, as the case group, and 100 healthy children, as the control group, were selected using convenient sampling. For all children, demographic data checklists were filled, and physical examination, abdomen and pelvic ultrasound and other diagnostic measures (if necessary) were performed to evaluate the congenital urogenital abnormalities including anomalies of the penis and urethra, and disorders and anomalies of the scrotal contents. Results: Among 92 (100%) urogenital anomalies diagnosed, highest frequencies with 37 (40.2%), 26(28.2%) and 9 (9.7%) cases including hypospadias, Cryptorchidism, and hydrocele, respectively. The frequency of urogenital abnormalities among 32 children with PCH, with 52 cases (56.5%) was significantly higher than the frequency of abnormalities among the 21 children in the control group, with 40 cases (43.4%). (OR=2.04; 95%CI: 1.1-3.6; p=0.014). Conclusion: Our study demonstrated that PCH is significantly associated with the congenital urogenital abnormalities. However, due to the lack of evidence in this area, further studies are recommended to determine the necessity of conducting screening programs for abnormalities of the urogenital system in children with CH at birth.

Emerging Concepts in Transitional Care of Congenital Genitourinary Reconstructions

Patients with congenital urogenital abnormalities represent a unique population with health care needs that often exceed the average urologic patient. Congenital uropathic patients, especially those with prior genitourinary reconstructions, display a range of bladder management strategies which must be meticulously managed by their urologist. The time encompassing the transition of care from the pediatric to the adult setting is a critical milestone that if left uncoordinated may result in the interruption of care and missed opportunities for disease prevention. During transition, the adult urologist should carefully assess the patient’s voiding habits, renal function and bladder function as well as new or worsening complaints. These complex patients require careful lifelong surveillance for evidence of almost inevitable changes in urinary function.

Relationship of congenital urogenital abnormalities and chromosomal abnormalities: a report of 200 cases

A total of 200 outpatients with congenital urogenital abnormalities were recruited. Peripheral blood from each patient had mixed lymphocyte culture and chromosome karyotype was analyzed. Among them, 22 (11%) cases showed abnormal chromosomal karyotypes. The aberrations included abnormal chromosome number (n=13), abnormal chromosome structure (n=8) and sex reversal syndrome (n=1). Chromosomal aberrations are important causative factors of congenital urogenital abnormalities. Key words: Chromosome aberrations; Sex reversal syndrome

A novel WT1 mutation in a 46,XY boy with congenital bilateral cryptorchidism, nystagmus and Wilms tumor

The WT1 gene plays a crucial role in urogenital and gonadal development. Germline WT1 alterations have been described in a wide spectrum of pathological conditions, including kidney diseases, genital abnormalities and Wilms tumor (WT), frequently occurring in combination. We report on a novel WT1 nonsense mutation (c.1105C>T), introducing a premature stop codon in exon 8 (p.Q369X), in a young XY male patient who presented with bilateral cryptorchidism, nystagmus, mild proteinuria and WT, but no sign of severe nephropathy. Although the majority of congenital urogenital abnormalities are not due to constitutional defects of the WT1 gene, our findings provide a rational for considering WT1 mutational analysis as one of the screening options in newborns with congenital defects of the urogenital tract due to the associated high risk of WT.

Multiple congenital urogenital abnormalities in a Tennessee Walking Horse colt

SummaryA 9‐month‐old, Tennessee Walking Horse colt was examined for urinary incontinence. Cystoscopy revealed a single identifiable ureter that appeared abnormal, and sabulous urolithiasis. Only the left kidney, which appeared lobulated and hydronephrotic, could be located using ultrasound. Results of serum chemistries were consistent with renal failure. Necropsy revealed unilateral agenesis of the right kidney and ureter with severe left ureterolithiasis, bilateral cryptorchidism and segmental aplasia of the ductus deferens. Histopathological examination revealed cystitis and diffuse interstitial fibrosis of the left kidney. Congenital malformations should be included as differential diagnoses for urinary incontinence and urogenital disease. Ultrasonography and cystoscopy can be useful to diagnose suspected agenesis of the urinary system in adult horses.

Gene expression analyses on embryonic external genitalia: identification of regulatory genes possibly involved in masculinization processes

Androgen plays a crucial role in initiating and maintaining the expression of male sexual characteristics in mammals. In humans and mice, any defects along the pathway of androgen functions result in congenital urogenital abnormalities. The genital tubercle (GT), an anlage of the external genitalia, differentiates into a penis in males and a clitoris in females. Although masculinization of the external genitalia is androgen-dependent, the molecular pathway of its potential downstream genes is largely unclear. To identify the genes involved in mouse GT masculinization, we performed gene expression analyses, such as real-time quantitative polymerase chain reaction and section in situ hybridization analysis. From our studies we have identified candidate genes, Cyp1b1, Fkbp51 and MafB as potential androgen targets during mouse GT masculinization.

Activin A: Autocrine Regulator of Kidney Development and Repair

The research described in this review suggests a novel and important role for activin A in the developmental and repair processes of the kidney (Table 1). The results obtained in these studies indicate that activin A is a negative regulator of kidney development and plays an essential part in kidney diseases, such as acute renal failure or renal fibrosis. It is also possible that activin A is a key player in the pathophysiological processes of other kidney diseases, such as congenital urogenital abnormalities, renal cystic disease and renal cell carcinoma. Activin A is thus a potential target for therapeutic interventions in kidney diseases. To address this issue, more detailed analysis on the regulation of activin production, modulation of activin activity and activin target genes is required.

The role of computed tomography in modern paediatric uroradiology

Computed tomography (CT) has developed a well-recognised role within paediatric uroradiology, especially in imaging of trauma, malignancy (in particular Wilms’ tumour), atypical infection, and congenital urogenital abnormalities. CT can also be used for problem solving in nephrolithiasis and renal transplant assessment. These applications are illustrated and discussed, with an emphasis on particular information that can be gained from the CT study.

LONG-TERM FOLLOW-UP OF REFLUX NEPHROPATHY IN ADULTS WITH VESICOURETERAL REFLUX - RADIOLOGICAL AND PATHOANATOMICAL ANALYSIS

To study the long-term development of urographic renal morphology in adults with vesicoureteral reflux, to investigate the relationship between renal damage and reflux grade, and to analyse the association between the long-term urographic outcome and the occurrence of acute pyelonephritis and reflux during follow-up. The purpose was also to try to distinguish between acquired and developmental renal damage, based on analyses of renal histological specimens and urographic features, and to analyse associated congenital urogenital abnormalities and family history of reflux, reflux nephropathy, urological malformation or death from end-stage renal disease. Renal damage was identified in 100 (83 women) of 115 adults, selected because of documented reflux. Eighty-seven patients had two urographies done (median interval 14.3 years). The extent and progression of renal damage were assessed and features of developmental renal damage were determined. Histological renal specimens were available in 23 patients with renal damage. The extent of renal damage correlated positively with the severity of reflux. No renal damage developed during the follow-up in 45 previously undamaged kidneys and progression of renal damage was rare (4 of 120 previously damaged kidneys), despite persisting reflux in half of the cases and episodes of acute pyelonephritis during follow-up. Thus, repeated renal imaging is rarely justified in adults with reflux nephropathy. Histological examination showed "chronic pyelonephritis" in all 23 cases and co-existing renal dysplasia in 1 case. The detailed urographic analysis did not reveal support for developmental renal damage. High frequencies of associated congenital urogenital abnormalities and of a positive family history were found. Thus, congenital and/or hereditary factors cannot be discarded as background factors for the development of renal damage.

Long-term follow-up of reflux nephropathy in adults with vesicoureteral reflux--radiological and pathoanatomical analysis.

To study the long-term development of urographic renal morphology in adults with vesicoureteral reflux, to investigate the relationship between renal damage and reflux grade, and to analyse the association between the long-term urographic outcome and the occurrence of acute pyelonephritis and reflux during follow-up. The purpose was also to try to distinguish between acquired and developmental renal damage, based on analyses of renal histological specimens and urographic features, and to analyse associated congenital urogenital abnormalities and family history of reflux, reflux nephropathy, urological malformation or death from end-stage renal disease. Renal damage was identified in 100 (83 women) of 115 adults, selected because of documented reflux. Eighty-seven patients had two urographies done (median interval 14.3 years). The extent and progression of renal damage were assessed and features of developmental renal damage were determined. Histological renal specimens were available in 23 patients with renal damage. The extent of renal damage correlated positively with the severity of reflux. No renal damage developed during the follow-up in 45 previously undamaged kidneys and progression of renal damage was rare (4 of 120 previously damaged kidneys), despite persisting reflux in half of the cases and episodes of acute pyelonephritis during follow-up. Thus, repeated renal imaging is rarely justified in adults with reflux nephropathy. Histological examination showed "chronic pyelonephritis" in all 23 cases and co-existing renal dysplasia in 1 case. The detailed urographic analysis did not reveal support for developmental renal damage. High frequencies of associated congenital urogenital abnormalities and of a positive family history were found. Thus, congenital and/or hereditary factors cannot be discarded as background factors for the development of renal damage.

In vitro branching tubulogenesis: Implications for developmental and cystic disorders, nephron number, renal repair, and nephron engineering

Branching tubulogenesis of the ureteric bud is critically important for kidney development. Recent findings using three-dimensional cell culture systems for in vitro branching tubulogenesis are likely to shed light on the mechanisms of ureteric bud morphogenesis. Here, we try to unify these findings with those obtained using genetic approaches and organ culture of the embryonic kidney into a working model of ureteric bud branching tubulogenesis. It appears that the balance between branching tubulogenesis facilitating growth factors such as epidermal growth factor receptor ligands, hepatocyte growth factor, insulin-like growth factors, and inhibitory growth factors such as transforming growth factor beta family members may regulate branching morphogenesis. Growth factors induce epithelial cell proliferation, migration, and modulate the expression of a variety of proteins. Downstream in the growth factor-mediated tubulogenesis pathway, extracellular proteases, protease inhibitors, extracellular matrix proteins, and integrins are likely to act as effectors and regulators of branching tubulogenesis. Discussed in some detail are the relevance of insights gleaned from in vitro models of branching tubulogenesis to congenital urogenital abnormalities, cystic kidney diseases, oligonephropathies and hypertension, tubular cell regeneration after injury, and tubular engineering.

Anaphylaxis to Natural Rubber Latex in a Girl with Food Allergy

Over the past few years, an increase in intraoperative and obstetric anaphylactic episodes has been related to rubber exposure. Individuals at high-risk for sensitization to latex include health care workers,1,2 rubber industry professionals,3 and children with spina bifida or congenital urogenital abnormalities who undergo frequent medical procedures.4,5 However, severe reactions have been observed in other subjects.6,7 Therefore, identifying patients at risk for anaphylaxis is essential before performing medical procedures involving rubber exposure. Recently,8 similarities in the protein content between natural rubber and several fruits have been found. Those proteins are cross-reactive and may cause severe allergic reactions if the patient comes in contact with rubber products and eats fruit.