Development of upper tract stones in patients with congenital neurogenic bladder

ObjectivePatients with neurogenic bladder are at increased risk of developing upper tract stones. We hypothesized that patients with lower urinary tract stone disease are at greater risk of developing upper tract stones.MethodsWe performed a 10-year retrospective case–control study of patients with neurogenic bladder to determine the association between bladder and upper tract stones. Independent risk factors for upper tract stones were assessed. Cases and controls were matched 1:1. Univariable analysis was performed by Fisher's exact test and the Mann–Whitney U test. Multivariable logistic regression was performed.Results52 cases and controls were identified. Cases were significantly more likely to be non-ambulatory, have bowel–urinary tract interposition, thoracic level dysraphism, and history of bladder stones. On multivariable analysis, independent predictors of stone formation were male sex (OR 2.82; p = 0.02), dysraphism involving the thoracic spine (OR 3.37; p = 0.014) bowel–urinary tract interposition (OR 2.611; p = 0.038), and a history of bladder stones (OR 3.57; p = 0.015).ConclusionPatients with neurogenic bladder are at increased risk for upper tract stones. The presence of bladder stones may herald the development of upper tract stones. The predictors of stone disease identified should guide prospective studies to better understand the natural history of upper tract stone development in this population.     

Scrotal pop off in a congenital anterior urethral diverticulum

Introduction and objectiveCongenital anterior urethral diverticulum is a rare entity. This teaching video shows the scrotal pop-off mechanism for an anterior urethral diverticulum and the unique voiding pattern of a boy who empties his bladder by compression of his scrotum. The findings during urethroscopy and open reconstruction are also demonstrated.Patient and methodsA four-year-old boy presented to the clinic with a poor urinary stream and scrotal swelling during voiding. Physical examination during voiding revealed a dumbbell-shaped anterior urethral diverticulum with scrotal pop off and preserved renal function.ResultsOpen excision of the scrotal part of diverticulum was performed. Urethroplasty was conducted using a de-epithelialised diverticular wall flap from the penobulbar urethra. On follow up the boy voided with a good flow and resolution of symptoms.ConclusionScrotal pop off with completion of voiding by manual compression of the diverticulum may preserve bladder and renal function. The preferred treatment of anterior urethral diverticulum is open excision of the diverticulum and reconstruction. The wall of the diverticulum may be used to reinforce the repair ventrally, where the corpus spongiosum is deficient.     

Cumulative incidence of outcomes and urologic procedures after augmentation cystoplasty

ObjectiveAugmentation cystoplasty (AC) is a major surgery that can be associated with long-term morbidity. This study aimed to describe the cumulative incidence of outcomes and urologic procedures in a large cohort of children who underwent AC, identify significant sources of morbidity, and to evaluate baseline factors associated with outcomes of interest.MethodsChildren ≤18 years who underwent AC in the Pediatric Health Information System from 1999 to 2010 were included. All follow-up encounters up to June 2012 were included. Cumulative incidences for 15 outcomes and urologic procedures were calculated using non-informative censoring. Sensitivity analyses were performed to determine effect of censoring assumptions and including hospitals without complete datasets. As an exploratory analysis, baseline patient factors were evaluated for associations with outcomes and urologic procedures of interest using multivariable Cox proportional hazards models adjusted for clustering by hospital.Results2831 AC patients were identified. Based on cumulative incidence calculations and sensitivity analyses; the cumulative incidence ranges of outcomes and procedures at 1, 3, 5, and 10 years were calculated. Examples of 10-year cumulative incidence ranges are given for the following outcomes and procedures: bladder rupture (2.9–6.4%), small bowel obstruction (5.2–10.3%), bladder stones (13.3–36.0%), pyelonephritis (16.1–37.1%), cystolithopaxy (13.3–35.1%), and reaugmentation (5.2–13.4%). The development of chronic kidney disease was strongly associated with a diagnosis of lower urinary tract obstruction (HR 13.7; 95% CI 9.4–19.9). Bladder neck surgery and stoma creation at time of AC were associated with an increased hazard of bladder rupture (HR 1.9; 95% CI 1.1–3.3) and bladder stones (HR 1.4; 95% CI 1.1–1.8) respectively.ConclusionsOutcomes of interest and urologic procedures after AC are common. Results from this large cohort can be used to counsel patients and families about expectations after AC. Pyelonephritis, chronic kidney disease, further reconstructive surgery, and calculus disease appear to cause significant morbidity. Collaborative efforts are needed to further reduce morbidity in this patient population.     

Genetic or pharmacologic disruption of the calcineurin-nuclear factor of activated T-cells axis prevents social stress-induced voiding dysfunction in a murine model

ObjectiveSocial stress can suppress the voiding reflex, with resultant diminished voiding frequency and increased volumes. The calcineurin-NFAT (nuclear factor of activated T cells) pathway is important in memory development. It was hypothesized that interruption of the calcineurin-NFAT pathway might prevent social stress-induced voiding dysfunction.MethodsMice were subjected to social stress in an established resident-intruder model for 1 h, followed by 23 h of barrier separation. NFATc3, NFATc4 knockout (KO) and wild-type (WT) mice were studied. At two weeks, voiding patterns were collected; this was followed by sacrifice. Corticotropin-releasing factor (CRF) mRNA expression in Barrington's nucleus (BN) was determined by in-situ hybridization.ResultsSocial stress decreased voiding frequency and increased voided volumes in WT strains. At baseline, NFATc3 KO mice showed decreased voids and increased volumes, while the NFATc4 KO mice resisted social stress. However, CRF mRNA increased in WT mice following social stress and was increased at baseline in NFATc3 KO mice. It was found that CRF mRNA did not increase following social stress in NFATc4 KO mice. The administration of CsA to WT mice normalized voiding patterns following social stress, albeit with no effect on CRF mRNA in BN.ConclusionDisrupting the calcineurin-NFAT axis by either genetic or pharmacologic approaches confers resistance to the development of social stress-induced voiding and dysfunction.     

Continuous antibiotic prophylaxis reduces the risk of febrile UTI in children with asymptomatic antenatal hydronephrosis with either ureteral dilation,high-grade vesicoureteral reflux,or ureterovesical junction obstruction

BackgroundThe efficacy and utility of continuous antibiotic prophylaxis (CAP) in children with congenital antenatal hydronephrosis (ANH) is uncertain. The literature has both supportive and contradictory evidence. The growing trend not to place children with ANH on CAP has created varied clinical practice based on anecdotal individual case characteristics. Our goal was to compare individual infant characteristics between those children who were maintained on CAP to those that were not to try to determine predisposing risk factors to febrile.MethodsAll electronic medical records (EMRs) of children referred to our institution for congenital ANH over a period from 2001 to 2011 were examined. We excluded those referred for urinary tract infection (UTI) who had a history of congenital ANH. We also excluded those with incomplete records, or follow-up less than 2 years. Children were divided into two groups: those maintained on CAP (YCAP) and those not maintained on CAP (NCAP). Our primary endpoint was febrile UTI. Follow-up was at least 24 months. Demographic, perinatal and postnatal clinical data were recorded. Statistical analysis was performed using STATA Version 11.1.ResultsOf the 405 children fitting inclusion criteria, 278 (68.6%) children were maintained on CAP and 127 (31.4%) were not on CAP. The incidence of prematurity, oligohydramnios, perinatal respiratory complications, use of perinatal antibiotics, circumcision status, renal anomalies, associated medical diagnoses, and low birth weight did not differ between the two groups. Overall the incidence of febrile UTI during the follow-up period was 22.2%. The incidence of febrile UTI between the YCAP and NCAP groups was significant (YCAP = 7.9% and NCAP 18.7%, p = 0.021). Multivariate logistic regression using CAP as the dichotomous dependent variable revealed that ureteral dilation, high-grade vesicoureteral reflux (VUR), and ureterovesical junction (UVJ) obstruction were independent risk factors for febrile UTI. More specifically, children with ureteral dilation >11 mm NOT maintained on CAP had a 5.54 (OR = 5.54; CI = 3.15–7.42, p = 0.001) fold increased risk of febrile UTI compared to those maintained on CAP.ConclusionsThe presence of ureteral dilation, high grade VUR, and UVJ obstruction were independent risk factors for development of UTI in children with congenital ANH. Therefore CAP may have a significant role in reducing the risk of febrile UTI in children with ANH with those identifiable risk factors, but otherwise seems unnecessary.     

Pediatric laparo-endoscopic single site partial nephrectomy: Feasibility in infants and small children for upper urinary tract duplication anomalies

ObjectiveTo assess the feasibility and outcomes of laparo-endoscopic single site (LESS) partial nephrectomy (PN) in infants and small children for upper urinary tract duplication anomalies.Materials and methodsThe medical records of all patients undergoing LESS PN at a single pediatric institution were retrospectively reviewed for patient demographics, perioperative details, and outcomes. A cystoscopy was initially performed to place an externalized catheter into the ureter of the ipsilateral normal renal moiety. An Olympus TriPort, an Olympus Endoeye flexible tip laparoscope, standard 3- or 5-mm instrumentation, and a LigaSure Blunt were utilized.ResultsFour children (two boys, two girls) underwent LESS PN. Three patients underwent upper pole PN and one underwent lower pole PN. All procedures were performed for poorly functioning obstructed renal moieties (one ureterocele, one ureteropelvic junction obstruction and vesicoureteral reflux, and two ectopic ureters). Median age was 6.2 months (range 2.5–16.4 months). Median weight was 7.7 kg (range 6.1–12.6 kg). Median operative time was 126 min (range 97–180 min). No patient received inpatient postoperative narcotics. Median follow-up was 9.9 months (range 6.2–19.1 months). No postoperative complications were noted. Postoperative renal ultrasound demonstrated successful resection in all patients.ConclusionsLESS PN is technically feasible, safe, and effective for upper urinary tract duplication anomalies in infants and small children.     

Management of obstructive calcular anuria with acute renal failure in children less than 4 years in age: A protocol for initial urinary drainage in relation to planned definitive stone management

ObjectivesTo describe and evaluate our protocol for management of children ≤4years old with obstructive calcular anuria (OCA) and acute renal failure (ARF) to improve selection of initial urinary drainage (ID) method and to facilitate subsequent definitive stone management (DSM) as studies discussing this special group of patients are still few.Patients and methodsPatients with a contraindication to any method of ID were excluded. Decision (percutaneous nephrostomy (PCN) or double J (JJ) stent) was based on degree of hydronephrosis and planned DSM. We used 4.8–5Fr JJ or 6–8Fr PCN under general anesthesia and fluoroscopic guidance. According to our protocol, JJ is inserted for hydronephrosis ≤ grade 1. When the hydronephrosis is >grade 1, patients with radiolucent stones were treated by JJ whatever the site of the stone. When the stones were radiopaque, PCN was reserved for stones in a solitary functioning kidney and bilateral ureteric stones prepared for subsequent bilateral ureterolithotomy (or stone prepared for ureterolithotomy in a solitary kidney). After normalization of renal functions, DSM was staged attacking only one side before discharge. Both sides were cleared at the same session in cases with bilateral ureterolithotomy. Renal or ureteric stones suitable for SWL in a solitary kidney were treated with percutaneous nephrolithotripsy (PNL) or ureteroscopy. This was followed also in patients with bilateral stones suitable for SWL by clearing one side using ureteroscopy or PNL before discharge. Open surgery (OS) was reserved for cases with failed ureteroscopy or PNL, for ureteric stones >2.5 cm in size or very large volume complex renal stones. Stone free rate (SFR) was evaluated by CT. Our protocol was evaluated as regard recovery of renal functions, complications, and number of interventions to clear stones.ResultsThis study included 62 boys and 22 girls presented with anuria for 1–4 days. JJ and PCN were inserted in 105 and 30 ureterorenal units (URU), respectively. Creatinine returns normal within 72 h. JJ insertion formed a part of DSM in 78/159 (49%) URU (stones prepared for extracorporeal shockwave lithotripsy or oral chemolytic dissolution therapy). PCN was the ideal tract for subsequent PNL in 11/159 (6.9%) URU. Accordingly, ID participated by 55.97% in DSM. Both operative and imaging times were slightly longer with PCN than JJ. There was no statistically significant difference in the insertion success or mean period to return to normal chemistry. Complications of both methods were mild and without any significant difference. Endourologic procedures constituted the majority of our interventions. Open surgical and endoscopic interventions for clearance of stones (including ID, treatment conversion and 2ry procedures) were done once for 25 patients, twice for 43 patients while it was needed three times for 16 patients. Total number of interventions was 149 procedures. SFR was 94%.ConclusionOur protocol ensures adequate ID with minimal complications when using our selection criteria in children ≤4 years in age with OCA and ARF. It also minimizes number of subsequent procedures to clear stones. Complications and success in insertion and drainage were equivalent in PCN and JJ groups.     

Lipid profile and some cardiac functions in children with obesity

BackgroundRisk factors of childhood obesity include; energy intake, positive family history and lifestyle. Obesity is associated with numerous co-morbidities such as cardiovascular diseases and type 2 diabetes.ObjectiveTo study serum lipid profile and evaluate the left ventricular systolic and global functions in obese children, and define the preclinical effects of obesity, per se, on myocardial function and cardiovascular system.Patients and methodsThis is a 9-Month prospective controlled study, done in Pediatrics Department Tanta University Hospital. 30 patients were included (24 males, six females); aged 6–15 years with BMI > age and sex specific cut off points. Exclusion criteria included organic causes of obesity, hormonal medications, corticosteroids, hypertension and diabetes mellitus. Twenty healthy children age and sex matched were set as the control group. Studied children were subjected to: anthropometric measurements: weight, height and BMI. Echocardiographic evaluation: LVEF, LVFS, LVEDD, predicted LVEDD, % LVEDD, LVM, LVMI and LMPI. Lipid profile assessment: included serum TCh, LDL, TCh/HDL ratio and TG.ResultsThere was highly significant increase in body weight, serum TCh, LVEDD, LVM and LVMI; significant increase in BMI, LDL, HDL, serum TG, TCh/HDL-cholesterol ratio, % LVEDD, predicted LVEDD and LMPI of obese as compared to controls. There was no significant difference between the two studied groups as regards height, LVEF and LVFS. There was significant decrease in HDL in obese patients as compared to the control group.ConclusionsComplete evaluation of cardiac function in obese children should include echocardiography along with LMPI (useful marker for early detection of LV global dysfunction), in combination with measurement of lipid profile.     

Endocrine effects of valproic acid therapy in girls with epilepsy: A prospective study

Background/aimIt is controversial whether the endocrine dysfunction in epilepsy patients is caused by the epilepsy itself, the antiepileptic therapy, or both. We prospectively evaluated the long-term impact of valproic acid monotherapy compared to other anti-epileptic drugs on anthropometric, metabolic, hormonal, and ultrasonographic parameters in girls with epilepsy.MethodsFifty-seven female patients with epilepsy who had started therapy at mean age of 11.5 ± 3.3 years, 42 with valproic acid (mean dose 13.1 ± 7.0 mg/kg/day and 15 with other anti-epileptic agents were followed for a mean of 3.2 years (range 1.0–8.5 years) in our center. Clinical, hormonal and transabdominal pelvic ultrasound data were collected at 3 time points: before and 6–12 months after onset of anti-epileptic drug treatment; and at the last visit while patients were still taking anti-epileptic drugs.ResultsThere were no significant between-group differences regarding changes in height, body mass index standard deviation score, levels of glucose and insulin, or lipid and endocrine profile from first to last visits. Mean thyroid-stimulating hormone level increased significantly between first and last visit only in the valproic acid group (p < 0.001), with no significant difference in free T4 level over time or between groups. The rate of clinical polycystic ovary syndrome for the valproic acid group (11%) was comparable to that reported in healthy controls (5–10%).ConclusionsAdministration of valproic acid had no adverse effect on body weight, metabolic status or endocrine function over an average follow-up of 3.2 years. Valproic acid appears to be safe for use in girls with epilepsy.     

Validity of US norms for the Bayley Scales of Infant Development-III in Malawian children

ObjectiveMost psychometric tests originate from Europe and North America and have not been validated in other populations. We assessed the validity of United States (US)-based norms for the Bayley Scales of Infant and Toddler Development-III (BSID-III), a neurodevelopmental tool developed for and commonly used in the US, in Malawian children.MethodsWe constructed BSID-III norms for cognitive, fine motor (FM), gross motor (GM), expressive communication (EC) and receptive communication (RC) subtests using 5173 tests scores in 167 healthy Malawian children. Norms were generated using Generalized Additive Models for location, scale and shape, with age modeled continuously. Standard z-scores were used to classify neurodevelopmental delay. Weighted kappa statistics were used to compare the classification of neurological development using US-based and Malawian norms.ResultsFor all subtests, the mean raw scores in Malawian children were higher than the US normative scores at younger ages (approximately <6 months) after which the mean curves crossed and the US normative mean exceeded that of the Malawian sample and the age at which the curves crossed differed by subtest. Weighted kappa statistics for agreement between US and Malawian norms were 0.45 for cognitive, 0.48 for FM, 0.57 for GM, 0.50 for EC, and 0.44 for RC.ConclusionWe demonstrate that population reference curves for the BSID-III differ depending on the origin of the population. Reliance on US norm-based standardized scores resulted in misclassification of the neurological development of Malawian children, with the greatest potential for bias in the measurement of cognitive and language skills.     

Single incisional approach for reconstruction of hypospadias and concomitant inguinal hernia

ObjectiveTo demonstrate the feasibility, cosmetic outcome and therapeutic values of our single incisional approach in patients with both hypospadias and inguinal hernia (IH) in comparison with standard multiple incisional techniques.Materials and methodsSixty hypospadias-IH repairs were performed from February 2005 to February 2012. These patients were divided into two groups according to their age and hypospadias location. They were then separated randomly into multiple incision (MIG) and single incision (SIG) groups. Early and late complications were taken into consideration. Postoperative pain, need for analgesics, operative time, hospital stay and cosmetic results were recorded for further evaluation.ResultsPatients were followed up at 6-month intervals for up to 2 years postoperatively. Early and late complication rates were approximately the same in the two groups. 73.3% of patients in MIG and 96.6% in SIG attained an excellent cosmetic result according to two external surgeons. There was no case with poor cosmetic outcome in either group. More analgesic consumption was demanded in MIG patients.ConclusionThis method of surgery is reproducible with better cosmetic outcome and a slightly shorter hospital stay. It could be a viable option in the management of children with hypospadias and concomitant IH. Negligible postoperative pain and short operative time are the other advantages.     

Fetal renal anomaly: Factors that predict survival

ObjectiveTo find out the relative prevalence of renal anomalies detected in the antenatal period, and to look at factors that predict the postnatal outcome.MethodsIn this prospective study, all antenatal-detected renal anomalies booked at the tertiary health centre were evaluated and counselled. Aspects such as type of renal anomaly, oligohydramnios and presence of additional anomalies were noted. Stillborn babies underwent autopsy; all live born babies were followed for one year. Appropriate statistical analyses were performed to compare the antenatal factors with outcomes.ResultsRenal anomalies were detected in 136 out of 587 cases with major fetal anomalies. Most of the women were primiparous (65.4%). The mean gestation at presentation was 30 weeks; in 12 cases, diagnosis was possible before 20 weeks (8.8%). Antenatal hydronephrosis was the most commonly seen anomaly, with 61 cases; this was followed by bilateral cystic kidney in 50 cases. Out of the 136 cases, 12 (8.8%) underwent termination of pregnancy and 60 (44.1%) babies were stillborn. Autopsy was performed in 58 out of 72 (80.6%) cases after consent. Karyotyping was performed in 49 cases and abnormalities were detected in two (4.1%) of them. A total of 64 (47.1%) babies were live born; after one year, 49 (36.0%) of them were alive. Postnatal survival was highest in unilateral disease (85.7%). In cases with oligohydramnios, there was only 3.4% survival after one year; none of the cases with cystic kidney and oligohydramnios survived. The period of gestation at presentation of non-survivors was 25.9 weeks compared to 32.5 weeks with survivors. Among the cases with extra renal anomaly, 7.0% survived; none of the cases with associated cranio-vertebral defect or polydactyly survived after a year.ConclusionOut of the different renal pathologies that were diagnosed, survival was highest in the unilateral group. The factors associated with poor prognosis included bilateral disease, absence of amniotic fluid and presence of associated malformation.     

Epispadias in boys with an intact prepuce

ObjectiveTo present an overview of the clinical presentation and pathological anatomy, and the results of surgical correction of 7 cases of epispadias with intact prepuce; a rare condition that has only occasionally been reported in literature.Patients and methodsA retrospective search was performed in the surgical and diagnoses database between 1991 and 2011. Seven cases of epispadias with intact prepuce were identified. Five presented as a webbed and buried penis, 1 as phimosis and 1 with suspicion for congenital anomaly of the genitalia.ResultsIn 3 of 7 cases, epispadias was suspected or diagnosed at first presentation and could be surgically corrected in the first intervention. In the other 4 cases, epispadias was discovered during surgery, requiring an additional intervention to perform epispadias repair in 3 cases. One boy was diagnosed with glandular, 3 with coronal, 1 with shaft and 2 with penopubic epispadias. Epispadias repair was successful with regard to cosmesis and erectile function. Five patients developed normal continence after surgery, 1 after intensive urotherapy. An under average penile length was the main reported problem during follow-up.ConclusionIn the diagnostic process for a concealed penis, the possibility of epispadias should be considered. If epispadias is suspected or confirmed, epispadias repair can occur in the first intervention, reducing the number of additional interventions. Epispadias with intact prepuce appears to have a better prognosis concerning urinary continence compared to classical epispadias.     

A novel mutation of anti-Mullerian hormone gene in Persistent Mullerian Duct Syndrome presented with bilateral cryptorchidism: A case report

BackgroundWe report a novel mutation in a case of Persistent Mullerian Duct Syndrome (PMDS). PMDS is characterized by the persistence of female reproductive organs derivatives in a 46,XY subject due to the failure of the Mullerian duct to regress in utero. To date, 53 different mutations of the anti-Mullerian hormone (AMH) gene, including the present one, have been identified.Clinical caseA 2-week-old male presented with bilateral cryptorchidism and normal male external genitalia. His karyotype was 46,XY. hCG stimulation test was normal. At age 1 year and 4 months, he underwent laparoscopic surgery which revealed a uterus and fallopian tubes. The anti-Mullerian hormone (AMH) level was undetectable (<0.01 ng/mL). Diagnosis of Persistent Mullerian Duct Syndrome, probably due to an AMH mutation, was made.Genetic studiesA unique homozygous T to G base substitution was found at position 2219, near the middle of the exon 5, changing codon CTG to CGG in anti-Mullerian hormone (AMH) gene. This mutation causes leucine to be converted to arginine at position 426 belonging to a (L)RA(L)LLLKALQ highly conserved sequence in the AMH gene. Both parents are heterozygous for the mutation.ConclusionPersistent Mullerian Duct Syndrome (PMDS) is a rare cause of bilateral cryptorchidism, when in doubt the existence of Mullerian derivatives should be explored by laparoscopy. Assay of serum AMH helps to distinguish between mutations of AMH and AMH receptor. If serum AMH is very low or undetectable, sequencing of the AMH gene usually confirms the presence of a mutation.     

Impact of laparoscopy for diagnosis and treatment in patients with disorders of sex development

ObjectiveTo review laparoscopy in patients with disorders of sex development (DSD) in order to clarify its usefulness in diagnosis, devising subsequent therapeutic strategies and managing patients with various conditions.Patients and methodsBetween April 1992 and December 2012, 29 laparoscopic surgeries were performed in 25 DSD patients. Among them, ten were diagnostic laparoscopy including gonadal biopsy, and 19 were therapeutic laparoscopy. Surgical procedures and complications were evaluated.ResultsFor diagnostic laparoscopy, laparoscopic gonadal biopsy was performed in three patients. Inspection, with or without open gonadal biopsy, was performed on four out of seven patients with 46XY DSD or mixed gonadal dysgenesis (MGD). Additional surgery was planned and performed based on diagnostic laparoscopic findings in six out of seven patients. In the three patients with ovotesticular DSD, the gonadal pathology was diagnosed as: testis/ovary in one, testis/ovotestis in one and ovary/ovotestis in one – this was from the laparoscopic inspection and/or gonadal biopsy. However, the final diagnoses were bilateral ovotestis in two patients and ovary/ovotestis in one patient.For therapeutic laparoscopy, surgical procedures were: gonadectomy in 17 patients (bilateral in 13, unilateral in three, partial in two); hysterectomy in two patients; orchiopexy in one; and sigmoid vaginoplasty in one patient (included multiple procedures). There were no severe perioperative complications. In the four patients with a history of diagnostic laparoscopy, no severe intra-abdominal adhesions that would disturb therapeutic laparoscopic surgery were observed.ConclusionWhile diagnostic laparoscopy was helpful in devising a therapeutic surgical strategy in most of the patients with DSD who were suspected as having complex gonadal status or Müllerian duct derivatives, attention must be paid to precisely diagnosing the gonadal status in ovotesticular DSD. On the other hand, therapeutic laparoscopic surgeries were valuable procedures in treating DSD patients, even with a history of previous diagnostic laparoscopy.     

New advances in the pathophysiologic and radiologic basis of the exstrophy spectrum

The exstrophy–epispadias complex is a rare spectrum of anomalies affecting the genitourinary system, anterior abdominal wall, and pelvis. Recent advances in the repair of classic bladder exstrophy (CBE) and cloacal exstrophy (CE) have resulted in significant changes in outcomes of surgical management (including higher continence rate, fewer surgical complications, and better cosmesis) and health-related quality of life in these patients. These noteworthy changes resulted from advances in the pathophysiological and genetic backgrounds of this disease and better radiologic assessment of the three-dimensional anatomy of the bony pelvis and its musculature. A PubMed search was performed with the keyword exstrophy. The resulting literature pertaining to genetics, stem cells, imaging, tissue engineering, epidemiology, and endocrinology was reviewed. The following represents an overview of the advances in basic science understanding and imaging of the exstrophy–epispadias spectrum and discusses their possible and future effects on the management of CBE and CE.     

Confirmation of chromosomal microarray as a first-tier clinical diagnostic test for individuals with developmental delay,intellectual disability,autism spectrum disorders and dysmorphic features

Background and objectivesSubmicroscopic chromosomal rearrangements are the most common identifiable causes of intellectual disability and autism spectrum disorders associated with dysmorphic features. Chromosomal microarray (CMA) can detect copy number variants <1 Mb and identifies size and presence of known genes. The aim of this study was to demonstrate the usefulness of CMA, as a first-tier tool in detecting the etiology of unexplained intellectual disability/autism spectrum disorders (ID/ASDs) associated with dysmorphic features in a large cohort of pediatric patients.Patients and methodsWe studied 349 individuals; 223 males, 126 females, aged 5 months-19 years. Blood samples were analyzed with CMA at a resolution ranging from 1 Mb to 40 Kb. The imbalance was confirmed by FISH or qPCR. We considered copy number variants (CNVs) causative if the variant was responsible for a known syndrome, encompassed gene/s of known function, occurred de novo or, if inherited, the parent was variably affected, and/or the involved gene/s had been reported in association with ID/ASDs in dedicated databases.Results91 CNVs were detected in 77 (22.06%) patients: 5 (6.49%) of those presenting with borderline cognitive impairment, 54 (70.13%) with a variable degree of DD/ID, and 18/77 (23.38%) with ID of variable degree and ASDs. 16/77 (20.8%) patients had two different rearrangements. Deletions exceeded duplications (58 versus 33); 45.05% (41/91) of the detected CNVs were de novo, 45.05% (41/91) inherited, and 9.9% (9/91) unknown. The CNVs caused the phenotype in 57/77 (74%) patients; 12/57 (21.05%) had ASDs/ID, and 45/57 (78.95%) had DD/ID.ConclusionsOur study provides further evidence of the high diagnostic yield of CMA for genetic testing in children with unexplained ID/ASDs who had dysmorphic features. We confirm the value of CMA as the first-tier tool in the assessment of those conditions in the pediatric setting.     

Alternating hemiplegia of childhood in Denmark: Clinical manifestations and ATP1A3 mutation status

Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disorder characterized by early-onset recurrent distinctive hemiplegic episodes commonly accompanied by other paroxysmal features and developmental impairment. De novo mutations in ATP1A3 were recently identified as a genetic cause of AHC. To describe the entire Danish cohort of paediatric AHC patients we approached neuropaediatricians nationwide. All currently acknowledged Danish patients ≤16 years with AHC were genetically tested and seen by the same child neurologist (PU). Ten patients; seven girls and three boys were identified. Mean present age was 10.0 years (range 1–16). Mean age at presentation was 7.4 months (range 1–18 months). Sequencing of ATP1A3 in all ten patients revealed a pathogenic mutation in seven. Two females with moderate psychomotor impairment were heterozygous for the known p.G947R mutation, whereas one severely retarded boy was heterozygous for the common p.E815K mutation. The prevalent p.D801N mutation was identified in two moderate to severely retarded children. Interestingly, in a set of monochorionic male twins a novel p.D801E mutation was identified, underscoring that the asparagine at position 801 is a mutation hotspot. Three girls aged 5–13 years did not reveal any ATP1A3 mutations. They were rather mildly clinically affected and displayed a normal or near-normal psychomotor development. This is the first study of AHC in the Danish paediatric population. The patients harboured a wide range of psychomotor difficulties. Patients with no mutation detected tended to be less severely affected. Prevalence was approximately 1 per 100,000 children.     

Lower urinary tract dysfunction in children after intravesical ureteric reimplantation surgery under one year of age

ObjectiveTo report the results of a study conducted on voiding function in children who have undergone intravesical trans-trigonal Cohen ureteric reimplantation surgery before the age of one year.SubjectsTwenty-eight children (18 males, 10 females) had surgery at a mean age of 4.9 months (range 8–352 days).MethodsBladder function was assessed at a mean age of 7.3 years using questionnaires, the dysfunctional voiding scoring system, PinQ quality of life tool, uroflowmetry and post-void residuals.ResultsOf the total children, 72% had normal lower urinary tract (LUT) function. Eight children (28%) had evidence of LUT dysfunction, two had urge incontinence, two had giggle incontinence, two had voiding postponement, one had dysfunctional elimination syndrome and one had evidence of dysfunctional voiding. Five of the eight children were managed with continence physiotherapy (urotherapy) and one required ongoing anticholinergic therapy.ConclusionWhen compared to the published rates of LUT dysfunction in the general paediatric community, no evidence was found to suggest an increased incidence of bladder dysfunction in children undergoing intravesical Cohen ureteric reimplantation surgery under one year of age.     

Comparison of testicular volume differential calculations in adolescents with varicoceles

PurposeWe aimed to develop a conversion formula between different calculations for testicular volume asymmetry.Materials and methodsMale adolescents with varicoceles who underwent scrotal ultrasound were studied. Two formulas were analyzed: (1) testicular volume differential, TVDiff = (RTV – LTV)/(TTV), and (2) atrophy index, AI = (RTV – LTV)/(RTV). RTV, LTV, and TTV represent the right, left, and total testicular volume. Through transformations and regression a conversion formula between the calculations was derived.ResultsBased on 248 ultrasounds, a clear relationship between the two formulas was demonstrated: AI = ln[(1.97 × TVDiff) + 1], (p < 0.0001).ConclusionsDifferential testicular volumes can easily be converted from one formula to another with near-perfect accuracy. The formulas are essentially identical and interchangeable.