Validation of the French version of the Caregivers' Priorities and Child Health Index of Life with Disabilities questionnaire.

INTRODUCTION: The Caregivers' Priorities and Child Health Index of Life with Disabilities (CPCHILD) is a questionnaire that measures the health-related quality of life (HRQL) of children with cerebral palsy (CP). Though measuring HRQL is challenging in these children, it is a valuable help for medical decision-making. There is no questionnaire to assess HRQL in French-speaking children with severe CP. OBJECTIVE: To translate and adapt transculturally the CPCHILD questionnaire into French (CPCHILD-FV). MATERIAL AND METHODS: The CPCHILD was translated from English into French by forward and backward translation by independents translators. The questionnaire was then tested on 32 caregivers of patients with CP classified as GMFCS IV or V, remarks of caregivers were analyzed by an expert committee and, if necessary, modifications were performed. Internal consistency of the CPCHILD-FV was assessed using a sample of 32 parents or caregivers and test-retest reliability was assessed on a random sample of 10 patients. RESULTS: The translation and transcultural process resulted in a French version of the CPCHILD. Some items of the CPCHILD required careful discussion to ensure that items had the same meaning as in the original. Internal consistencies were over 0.70 for each domain except for health, and 0.97 for the total scores. The ICC for the test-retest reliability of the CHILD-FV total score was 0.98 (95% CI: 0.93-0.99) and ranged from 0.59 to 0.99 for the domains. CONCLUSION: The translation and cross-cultural adaptation of the CPCHILD questionnaire provides a French version than can measure the HRQL of children with severe CP. LEVEL OF EVIDENCE: IV; prospective study without control group.

Hypospadias preputial flap onlay technique - Step by step.

PURPOSE: To present one way of performing onlay preputial flap for hypospadias. PATIENTS AND METHODS: This procedure was performed following the methodology used in one hypospadias expert center to correct hypospadias in boys who are not elective for Koff procedure and in whom Koyanagi procedure is not needed. Operative details were described, and post-operative management were given as example. RESULTS: Long-term results of this technique showed a 10% complication rate (dehiscence, strictures or urethral fistulas) 2 years after surgery. CONCLUSIONS: This video is a step by step description of the onlay preputial flap technique giving the general methodology and also the details resulting from years of practice in one hypospadias expert center.

Changes in the clinical management of 5α-reductase type 2 and 17ß-hydroxysteroid dehydrogenase type 3 deficiencies in France.

Objectives: To examine the changes in diagnostic practices and clinical management of patients with 5α-reductase type 2 (SRD5A2) or 17ß-hydroxysteroid dehydrogenase type 3 (HSD17B3) deficiency since molecular diagnoses became available. Methods: Clinical, laboratory, and therapeutic data were retrieved from the medical records of 52 patients with a molecular diagnosis of SRD5A2 (n = 31) or HSD17B3 (n = 21) deficiency. Temporal trends regarding age at assessment and initial sex assignment over 1994-2020 were qualitatively analyzed. Age at molecular diagnosis was compared between two subgroups of patients according to their year of birth. Results: Fifty-eight percent (n = 30) patients were diagnosed during the perinatal period, 33% (n = 17) during infancy, and 9% (n = 5) during adolescence or adulthood. Over the studied period, the patients' age at initial assessment and diagnosis frankly decreased. The median (range) age at diagnostic confirmation was 10.5 (0-53.2) years for patients born before 2007 and 0.4 (0-9.3) years for those born in 2007 or later (P = 0.029). Genetic testing identified 27 different variants for the SRD5A2 gene (30% novel, n = 8) and 18 for the HSD17B3 gene (44% novel, n = 8). Before 2002, most patients were initially assigned as females (95%, n = 19), but this proportion dropped for those born later (44%, n = 14; P < 0.001). The influence of initial genital appearance on these decisions seemingly decreased in the most recent years. Therapeutic interventions differed according to the sex of rearing. Ten percent (n = 2) patients requested female-to-male reassignment during adulthood. Conclusion: This study showed, over the past two decades, a clear trend toward earlier diagnosis and assignment of affected newborns as males.

Steroid Profiling in the Amniotic Fluid: Reference Range for 12 Steroids and Interest in 21-Hydroxylase Deficiency.

CONTEXT: Determination of steroid levels in the amniotic fluid gives some insight on fetal adrenal and gonadal functions. OBJECTIVE: Our objectives were to establish reference ranges of 12 steroid levels throughout pregnancy and to compare them with steroid levels from pregnancies with fetuses presenting with 21-hydroxylase deficiency (21OHD). METHODS: Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was applied to 145 "control" amniotic fluid samples from gynecology activity (12 + 6 to 32 + 4 gestational weeks, GW). The following steroids were analyzed according to gestational age and compared to 23 amniotic fluid samples from fetuses with classic 21OHD confirmed by molecular studies: delta-4-androstenedione (D4), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), 11-deoxycortisol (11OH), 21-deoxycortisol (21OH), corticosterone, deoxycorticosterone (DOC), testosterone, pregnenolone, 17-hydroxypregnenolone (17Pregn), cortisol, and cortisone. Chromosomal sex was determined by karyotype and gestational age by biometric measurements. RESULTS: Analysis of control samples showed a statistically significant difference for D4 and testosterone levels according to fetal sex. Cortisol, corticosterone, and DOC had lower concentrations before 20 GW than after 20 GW, whereas 17Pregn and pregnenolone had higher concentrations before 20 GW. This allowed us to establish age- and sex-dependent reference values. We observed higher 21OH, 17Pregn, D4, and testosterone levels in females with 21OHD than female controls. The ratios 17OHP/17Pregn, D4/DHEA, and 11OH/17OHP appeared discriminant for the diagnosis of 21OHD. CONCLUSION: Our study provides information on fetal steroidogenesis and suggests reference values for 12 steroids during pregnancy. This allows a prenatal diagnosis of 21OHD within 24 hours and might be useful in the diagnosis of other variations of sex development.

Early detection of ureteropelvic junction obstruction in neonates with prenatal diagnosis of renal pelvis dilatation using 1H NMR urinary metabolomics.

Renal pelvis dilatation (RPD) is diagnosed in utero on prenatal ultrasonography (US) and can resolve spontaneously. However, isolated RPD can also reflect ureteropelvic junction obstruction (UPJO), which requires surgical treatment to prevent progressive renal deterioration. The diagnosis of UPJO can only be confirmed after birth with repeat US and renal isotope studies. 1H Nuclear Magnetic Resonance spectroscopy (NMR) was performed on urine of newborns with prenatally diagnosed unilateral RPD and healthy controls to identify specific urinary biomarkers for UPJO. The original combination of EigenMS normalization and sparse partial-least-squares discriminant analysis improved selectivity and sensitivity. In total, 140 urine samples from newborns were processed and 100 metabolites were identified. Correlation network identified discriminant metabolites in lower concentrations in UPJO patients. Two main metabolic pathways appeared to be impaired in patients with UPJO i.e. amino acid and betaine metabolism. In this prospective study, metabolic profiling of urine samples by NMR clearly distinguishes patients who required surgery for UPJO from patients with transient dilatations and controls. This study will pave the way for the use of metabolomics for the diagnosis of prenatal hydronephrosis in clinical routine.

Complication profile of augmentation cystoplasty in contemporary paediatric urology: a 20-year review.

BACKGROUND: The aim of this study was to describe the complication profile of augmentation cystoplasty in contemporary paediatric urology as well as its effect on bladder metrics. METHODS: Consecutive operative cases were retrospectively reviewed at a single institution over 20 years (1999-2019). Short- and long-term outcomes and complications following augmentation cystoplasty were defined. RESULTS: Of the 71 operative cases; the most common underlying diagnoses were neurogenic bladder (34%), exstrophy-epispadias complex (30%) and posterior urethral valves (23%). The most common tissue-type utilized was ileal (58%) and ureteric (30%). Peri-operative urine leak affected nine (13%) children but reservoir perforations were less common (4%). Mean end-of-study detrusor pressure improved significantly following bladder augmentation (38-17 cmH2 O, P < 0.001). Bladder capacity improved significantly (67-89%, P = 0.041). The median follow-up was 4.5 years (interquartile range: 1.9-10 years). Bladder urolithiasis affected 13 (18%) patients, and symptomatic urinary tract infections 36 (51%) patients. Formation of a continent catheterisable channel contributed a number of complications relating predominantly to stenosis (50%). Repeat augmentation cystoplasty was necessary in three (4%) cases. CONCLUSION: Augmentation cystoplasty is a surgical intervention that improves bladder metrics. Given the potential complications, careful patient selection and appropriate pre-operative counselling are essential. Furthermore, pro-active post-operative management and transitional care are vital in the surgical care of children following augmentation cystoplasty.

Genetic Analysis Reveals Complete Androgen Insensitivity Syndrome in Female Children Surgically Treated for Inguinal Hernia.

Background: Complete androgen insensitivity syndrome (CAIS) is a congenital condition caused by genetic defects in the androgen receptor (AR) gene located on the X chromosome, which lead to a phenotypical female individual with a 46, XY karyotype. Early diagnosis of CAIS is essential for proper clinical management, allows assessment of familial risk and contributes to healthcare decisions. However, diagnosis of CAIS can be overlooked in girls with inguinal hernia, resulting in inappropriate management. Methods: Five female patients from three unrelated families presented to our genetic clinic with primary amenorrhea. Each patient had been diagnosed with inguinal hernia in childhood and had undergone hernia repair without further investigation into what was contained in the hernial sac. We carried out physical examination, cytogenetic studies, hormonal evaluation, and molecular analysis to establish a comprehensive diagnosis. Family history and pedigree were collated to identify at-risk family members. Results: All patients presented with female external genitalia. Cytogenetic studies revealed a 46, XY karyotype and hormonal analysis suggested a diagnosis of CAIS. Sequencing of the AR gene in all patients and suspected family members revealed pathogenic variants in the AR gene and confirmed the molecular diagnosis of CAIS. Conclusions: We report the delayed diagnosis of CAIS in female Indonesian patients with a history of inguinal hernia in childhood. An early diagnosis of CAIS is essential for appropriate clinical management, as well as assessing familial risk. Increasing awareness among clinicians is paramount, and we encourage a CAIS diagnosis to be considered in any patient presenting with female appearance and inguinal hernia.

Minimally invasive surgery for unilateral Wilms tumors: Multicenter retrospective analysis of 50 transperitoneal laparoscopic total nephrectomies.

PURPOSE: To evaluate feasibility and outcomes of minimally invasive surgery (MIS) in Wilms tumor (WT). METHODS: International multicenter review of MIS total nephrectomies for WT between 2006 and 2018. Medical records of confirmed WT were retrospectively assessed for demographic, imaging, treatment, pathology, and oncological outcome data. RESULTS: Fifty patients, with a median age of 38 months (6-181), were included in 10 centers. All patients received neoadjuvant chemotherapy, as per SIOP protocol. Median tumor volume post-chemotherapy was 673 mL (18-3331), 16 tumors crossed the lateral border of the spine, and three crossed the midline. Six patients with tumors that crossed the lateral border of the spine (tumor volumes 1560 mL [299-2480]) were converted to an open approach. There was no intraoperative tumor rupture. Overall, MIS was completed in 19% of the 195 nephrectomies for WT presenting during the study period. Tumor was stage I in 29, II in 16, and III in 5, and histology was reported as low in three, intermediate in 42, and high risk in five. Three patients had positive tumor margins. After a median follow-up of 34 months (2-138), there were two local recurrences (both stage I, intermediate risk, 7 and 9 months after surgery) and one metastatic relapse (stage III, high risk, four months after surgery). The three-year event-free survival was 94%. CONCLUSION: MIS is feasible in 20% of WT, with oncological outcomes comparable with open surgery, no intraoperative rupture, and a low rate of local relapse. Ongoing surveillance is, however, needed to evaluate this technique as it becomes widespread.

Functional Characterization of Two New Variants in the Bone Morphogenetic Protein 7 Prodomain in Two Pairs of Monozygotic Twins With Hypospadias.

CONTEXT: Variants in bone morphogenetic protein 7 (BMP7) have been reported in patients with hypospadias. Here we report and analyze two variants in the BMP7 prodomain in monozygotic twins with hypospadias. MATERIALS AND METHODS: Patients with hypospadias were prospectively recruited. After informed consent was obtained, DNA was extracted from blood. The coding regions of 1034 genes [including 64 known diagnostic genes and candidate genes for disorder/difference of sex development (DSD)] were sequenced using a targeted capture approach (HaloPlex, Agilent, Santa Clara, CA), combined with massively parallel sequencing. The resulting variants were filtered for rarity in the general population (<1%) and in our screen. Quality, depth of the reads, and predicted pathogenicity were also considered. The consequences of the identified mutations on BMP7 expression was determined by Western blot analysis on culture media from transfected cells, and activity measured using a SMAD 1/5-responsiveness luciferase assay. RESULTS: We analyzed DNA from 46 patients with hypospadias. Two variants in BMP7 were identified in two pairs of monozygotic concordant twins exhibiting proximal hypospadias. Both variants are heterozygous, nonsynonymous, and affect highly conserved amino acids in the prodomain of BMP7 in regions predicted to be important for BMP7 assembly/folding. Functional analyses demonstrated that both variants disrupt BMP7 synthesis or secretion. CONCLUSION: Through our targeted DSD panel we have identified two variants in the prodomain of BMP7 in hypospadias. By decreasing BMP7 synthesis, these variants are likely to limit BMP7 bioavailability during closure of the urethral plate.Further analysis of patients with hypospadias may uncover additional variants that cause this DSD.

What is the risk of local recurrence after laparoscopic transperitoneal radical nephrectomy in children with Wilms tumours? Analysis of a local series and review of the literature.

BACKGROUND: To reduce long-term morbidity (adhesions-related complications and impaired quality of life due to scars), laparoscopy has been used as an alternative to open surgery in Wilms tumours (WTs). However, concerns have been raised on the risk of local recurrence after this type of resection. OBJECTIVE: The aim was to determine the incidence of local recurrence after laparoscopic transperitoneal radical nephrectomy (LTRN). STUDY DESIGN: We analysed 18 local cases and conducted a review of the English literature in Pubmed from 2004 to 2017 with the following keywords: (Wilms OR nephroblastoma) AND (laparoscopy OR minimally invasive surgery) AND 2004:3000. The review was conducted according to PRISMA guidelines. Data were collected independently in duplicate in a preformed Excel database. Review articles and duplicated case reports were excluded. Patients with retroperitoneoscopic or nephron-sparing surgery were also excluded. RESULTS: One hundred and four LTRNs have been performed for WT with neoadjuvant chemotherapy in 93 cases. Tumour was ruptured preoperatively in three cases but never intraoperatively. The median volume of the tumour was 229.4 mL (3.8-776 mL). Local stage was specified in 86 cases: 49 stage I, 28 stage II, and nine stage III. Lymph nodes were sampled in 48 patients (median 2.3 [0-14] nodes). Histology was reported in 90 cases: 27 favourable and two unfavourable histology (COG); and six low, 50 intermediate, and five high-risk tumours (International Society of Paediatric Oncology). With a median follow-up of 20.5 months (1-114 months), there were four local recurrences (3.8%) at a median of 8.5 (7-9) months after surgery. Three tumours were initial local stage I (2 intermediate and 1 high risk) and one stage III. The results are presented in the Figure. DISCUSSION: The incidence of local recurrence after LTRN is 3.8%. This is lower than previously reported after open resection. However, tumours amenable to minimally invasive surgery are smaller, with higher numbers of low stage and standard histology. Additionally, the quality of the reports is suboptimal and follow-up is relatively short. CONCLUSION: LTRN does not seem to increase the incidence of local recurrence in WT but inclusion of patients in international protocols with prolonged and systematic follow-up is of utmost importance to carefully evaluate this risk.

Bladder Dysfunction in Children with Neurofibromatosis Type I: Report of Four Cases and Review of the Literature.

AIM: Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disorder. Malignant transformation into malignant peripheral nerve sheath tumors (MPNST) can occur. However, urinary tract involvement is rare. We report 4 cases of NF1 with bladder dysfunction. METHODS: A retrospective single center analysis of 4 patients was conducted over a 17-year period, focusing on urinary tract involvement. RESULTS: NF1 was diagnosed at a median of 16.5 months (4-36) and urinary involvement occurred at a median of 5.25 years (4-9) after diagnosis. Bladder dysfunction was due to spinal cord compression in 2 cases, bladder invasion in 1 case, and cerebral lesions in 1 case. Malignant transformation of neurofibromas into MPNST occurred in 2 patients. Mechanisms of urinary involvement in NF1 are diverse and no pre-established protocol of management and follow-up exists. CONCLUSION: Although rare, dysfunction of the bladder can arise in NF1 and innovative strategies then need to be considered. This is best achieved with the help of a multidisciplinary team and a national reference center when available.

Laparoscopic nephrectomy for Wilms' tumor: Can we expand on the current SIOP criteria?

INTRODUCTION: Wilms' tumor now has a good overall prognosis with open radical nephrectomy having been the mainstay of surgical treatment. Recently laparoscopic nephrectomy (LN) has been growing in popularity. The aim of our study was to review our indications and outcomes for laparoscopic resections for Wilms' tumor and compare indications with International Society of Paediatric Oncology (SIOP) criteria for LN. MATERIAL AND METHODS: Patient demographics, preoperative management, surgical data, respect of SIOP criteria, complications, disease outcome, and follow-up were recorded on consecutive children who underwent nephrectomy for Wilms' tumor. RESULTS AND DISCUSSION: Fifty-four consecutive children with Wilms' tumor underwent a nephrectomy; 20 had a LN (Table). Nine of 20 (45%) patients who had LN did not meet SIOP criteria for LN. No patients had an intraoperative tumor rupture and one patient had positive margins because of preoperative rupture. There were two conversions: one caused by difficulty accessing the renal hilum and the other caused by difficulty maintaining oxygen saturations. There was one local recurrence. CONCLUSION: SIOP criteria are conservative and safe. Indications can be extended for teams experienced in surgical oncology and laparoscopy after agreement at a multidisciplinary meeting (MDM).

Variants in congenital hypogonadotrophic hypogonadism genes identified in an Indonesian cohort of 46,XY under-virilised boys.

BACKGROUND: Congenital hypogonadotrophic hypogonadism (CHH) and Kallmann syndrome (KS) are caused by disruption to the hypothalamic-pituitary-gonadal (H-P-G) axis. In particular, reduced production, secretion or action of gonadotrophin-releasing hormone (GnRH) is often responsible. Various genes, many of which play a role in the development and function of the GnRH neurons, have been implicated in these disorders. Clinically, CHH and KS are heterogeneous; however, in 46,XY patients, they can be characterised by under-virilisation phenotypes such as cryptorchidism and micropenis or delayed puberty. In rare cases, hypospadias may also be present. RESULTS: Here, we describe genetic mutational analysis of CHH genes in Indonesian 46,XY disorder of sex development patients with under-virilisation. We present 11 male patients with varying degrees of under-virilisation who have rare variants in known CHH genes. Interestingly, many of these patients had hypospadias. CONCLUSIONS: We postulate that variants in CHH genes, in particular PROKR2, PROK2, WDR11 and FGFR1 with CHD7, may contribute to under-virilisation phenotypes including hypospadias in Indonesia.

Critical Analysis of a Series of Early Inguinal Ureterostomies: Are They Useful and How Well Are They Tolerated?

INTRODUCTION: The study aimed to evaluate the advantages of temporary inguinal ureterostomy in the management of neonates with uropathies and early or recurrent pyelonephritis. PATIENTS AND METHODS: We performed a retrospective analysis of all patients who underwent ureterostomies between 1989 and 2012, with specific regards to indications and outcomes. We also performed a survey of parents to evaluate their acceptance of diversion. RESULTS: We included 18 patients (12 primary high-grade vesicoureteral reflux [VUR] and 6 primary obstructive megaureters [MUs]). Indications were recurrent febrile urinary tract infections (UTIs) despite antibiotic prophylaxis, doubtful function of the overlying kidney for the oldest cases, when renal function was only assessed by intravenous urography, or both. Cutaneous diversion was performed between the ages of 2 weeks to 5 months (median: 1.8 months). Renal function was assessed prior to undiversion to choose between reimplantation and nephrectomy. The incidence of febrile UTIs significantly decreased during the period of diversion. Urinary diversion was judged socially acceptable by parents. Ureterostomy did not modify the overlying kidney function. CONCLUSION: Temporary inguinal ureterostomy does not enable better evaluation of renal function by suppressing the pressure of an obstacle or refluxing urines. Its remaining indication seems to be the prevention of recurrent UTIs in neonates and infants with VUR or MU, pending reimplantation.

Bladder continent catheterizable conduit (the Mitrofanoff procedure): Long-term issues that should not be underestimated.

BACKGROUND: Effective bladder emptying by clean intermittent catheterization for children with severe bladder dysfunction is critical for renal preservation and social integration. Use of a continent catheterizable conduit (CCC) as urethral alternative procedure provides effective bladder drainage. However, it brings a substantive maintenance. METHODS: Retrospective review of the indications and long-term outcomes of 54 patients with a Mitrofanoff procedure in a single center over a 20-year period (1995-2015). RESULTS: Indications of CCC include 21 neurogenic bladders, 12 patients with epispadias/exstrophy, 13 bladder outlet obstruction, 6 malignancies and 2 cloaca. Median age at surgery was 8.3years (4months-20years). The appendix was used in 76% of cases. Most frequently encountered complication was stomal stenosis (n=17/34, 50%), occurring at median time of 9months (2months-13years). The other complications were: leakage in 9 (26.5%); conduit stricture in 5 (14.7%), angulation of the conduit in 2 (5.8%) and prolapse in one (3%). Operative revision was encountered by 33 (61%) patients, the majority in the first 2years. Median follow-up was 4.3years (3months-16years). CONCLUSIONS: CCC has a high incidence of complication. It has to be used only when the native urethra is not suitable for catheterization. Carers, patients and families must be prepared to deal with both the complexity of index conditions and the complications of this procedure.

Conservative treatment of pediatric thoracic and lumbar spinal fractures: outcomes in the sagittal plane.

To assess sagittal plane spinopelvic balance and functional outcomes in a pediatric cohort of patients with a thoracic and/or a lumbar fracture treated conservatively. A multicentric study retrospectively reviewed radiological and functional outcomes (mean follow-up 49 months) of 48 patients (mean age 12 years) with thoracic and/or lumbar spinal fractures that occurred between 1996 and 2014. Demographic data and radiological spinopelvic parameters were analyzed. Functional outcome was evaluated by a telephone interview. First, a comparison between the initial and the last follow-up full-spine radiographs was performed for the assessment of bone remodeling and sagittal plane balance. Then, patients were classified into two groups (group 1: Risser≤2 and group 2, Risser>2) to assess the influence of skeletal maturity on the restoration of a correct sagittal balance. A total of 62% of the patients were at skeletal maturity at the final follow-up (Risser 4 and 5). Patients with a Risser grade of 2 or less had a higher remodeling potential. The mean residual local kyphosis in thoracic and lumbar fractures was, respectively, 8.2° and 8.7°. The mean thoracic global kyphosis remains stable at the last follow-up, in contrast to lumbar lordosis, which increased significantly. Sagittal plane global measurements on the basis of the C7-plumbline remained unchanged at the last follow-up. There was no change in the pelvic parameters, except for the sacral slope in the group 1 for patients with a lumbar fracture. The current study confirms a greater correction in younger patients (Risser≤2) in spinal fractures and reported that thoracic fractures have a higher remodeling potential than lumbar fracture. A local kyphosis of almost 10° remained at the last follow-up. However, no deterioration in the sagittal plane balance was found. This suggests compensatory mechanisms in adjacent structures for children and adolescents and excludes the only hypothesis of bone remodeling.

Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort.

BACKGROUND: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. RESULTS: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46,XY DSD. In patients with 46,XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. CONCLUSIONS: Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes.

Two-stage graft urethroplasty for proximal and complicated hypospadias in children: A retrospective study.

INTRODUCTION: Although two-stage graft urethroplasty is widely used, the literature regarding the complication rates and functional characteristics of reconstructed neourethra is relatively modest. OBJECTIVES: The aim was to analyze the complication rates and uroflow data of boys who have previously undergone a two-stage graft urethroplasty procedure for proximal and complicated hypospadias. PATIENTS AND METHODS: We retrospectively reviewed the clinical outcomes of 52 boys with proximal (n = 44) and complicated (n = 8) hypospadias who underwent two-stage graft urethroplasty repair (median age of 15 months and 3 years respectively) between 2004 and 2015. Fifteen toilet-trained boys without fistulas underwent uroflowmetry. The uroflow data were plotted on age-volume-dependent normograms with normal controls. The median follow-up was 34 months (8 months-8 years). RESULTS AND COMPLICATIONS: Complications were identified in three patients (6%) after the first stage (i.e. contracture of the graft) and in 20 patients (38.4%) after the second stage, including meatal stenosis (n = 8, 15.3%), urethral stricture (n = 4, 7.6%), urethrocutaneous fistula (n = 8, 15.3%), glandular dehiscence (n = 1, 1.9%), and diverticulum (n = 1, 1.9%). The patients with failed hypospadias experienced fewer complications than those who underwent the two-stage procedure for primary repair (25% and 45%, respectively). The reoperation rate was 36.8%. Eleven of the 15 toilet-trained boys were asymptomatic but exhibited flow rates below the normal range (median Qmax = 7 mL/s, range 3.5-16.7). Only one of the boys with a low flow rate was confirmed to have urethral stenosis under general anesthesia. DISCUSSION: In our study, primary hypospadias repair requiring urethral plate transection elicited worse outcomes than those observed in the prior failed hypospadias cases. However, because of our study's retrospective design, we were unable to accurately assess the initial position of the meatus in the redo hypospadias cases. Our data also demonstrated that the majority of cases without any voiding symptoms exhibited flow rates that were below the normal range despite no urethral stricture under general anesthesia. These findings indicate that urethras reconstructed via two-stage graft urethroplasty repair are not functionally equivalent to normal urethras, at least prior to puberty. CONCLUSION: Two-stage graft urethroplasty repair was successful in 62% of cases after the second-stage procedure, but one-third of the boys required a reoperation after the two-stage planned repair. We demonstrated that although we used a urethral tissue substitute, the urine flow patterns of the patients without strictures were abnormal.

Testicular biopsy in prepubertal boys: a worthwhile minor surgical procedure?

No consensus exists regarding the precise role of testicular biopsy in prepubertal boys, although it is considered useful for assessing the potential consequences of undescended testes on fertility. Current scientific knowledge indicates that surgeons should broaden indications for this procedure. For example, the use of immunohistochemical markers such as OCT/3-4, TSPY, Kit ligand (SCF) and ALPP (PLAP) has considerably facilitated the detection of germ cell tumour precursors, such as carcinoma in situ and/or gonadoblastoma. These markers are very important for evaluating malignancy risk in undervirilized patients with 46,XY disorders of sexual development. Testicular histology is also of considerable value in the prediction of both fertility potential and risk of cancer in individuals with undescended testes, particularly those with intraabdominal undescended testes. New possibilities for the preservation of fertility after gonadotoxic chemotherapy - even for prepubertal boys - are emerging. Cryopreservation of testicular tissue samples for the preservation of fertility - although still an experimental method at present - is appealing in this context. In our opinion, testicular biopsy in prepubertal boys is a minor procedure that can provide valuable information for predicting the risk of malignancy and fertility, and might be useful in fertility preservation in the near future.

DICER1 pleuropulmonary blastoma familial tumour predisposition syndrome: What the paediatric urologist needs to know.

INTRODUCTION: Germline-inactivating DICER1 mutations are responsible of a familial tumour susceptibility syndrome with an increased risk of tumours, mainly pleuropulmonary blastoma (PPB). DICER1 mutations also cause a range of other tumours, some of them in urogenital organs (cystic nephroma [CN], ovarian sex cord-stromal tumours, bladder and cervix embryonal rhabdomyosarcoma [ERMS]). OBJECTIVE: The aim was to clarify the range of urogenital phenotypes associated with DICER1 mutations and to give practical course of action to paediatric urologist that are exposed to DICER1-related conditions. STUDY DESIGN: A literature review was performed. Pertinent papers focused on urogenital diseases associated with DICER1 mutations were reviewed. RESULTS: Seventy per cent of CN have a DICER1 germline mutation. The majority of them (80%) have PPB. Like PPB, CN could undergo a malignant progression to a primitive sarcoma. Some rare cases of Wilms tumours were reported. Regarding gonadal manifestations, sex-cord stromal neoplasia of the ovary, especially Sertoli-Leydig cell tumour (SLCT), is the most frequent tumour associated with DICER1 germline mutation. Germline DICER1 mutations also predispose to uterine cervix and bladder ERMS. DISCUSSION: The presence of unusual tumours suggesting DICER1 mutations may alert clinicians. The first step is to obtain a complete familial history. The variable clinical presentation and the modest penetrance raise concerns about the appropriateness of genetic testing to patients and their relatives. The education of DICER1 mutations carriers about tumour-related symptoms is consensual. In the first 5 years of life, a yearly chest X-ray and abdominal ultrasound are recommended. CONCLUSION: The presence of a CN, ovarian SLCT or urogenital ERMS in a child should alert the clinician to the possibility of DICER1 mutation and the associated risk of PPB. Individuals with one of the typical DICER1 conditions should be offered DICER1 analysis. Despite the low penetrance, a genetic counselling and testing should be offered to the family of the affected child.