Post-trauma scoliosis after conservative treatment of thoracolumbar spinal fracture in children and adolescents: results in 48 patients.

PURPOSE: Authors examined a case series of patients younger than 18 years old who had sustained a traumatic thoracolumbar spine fracture to evaluate radiological and clinical findings of coronal spinal balance, after conservative treatment. METHODS: From 1996 to 2014, a tricentric cohort of 48 patients with an average age of 12 years was radiographically reviewed at 50 months. Cobb angle of fractured vertebra and regional Cobb angle were measured both at baseline and follow-up. Analyses were done according to initial Risser grade, number of fractures and level of injury. RESULTS: There was a total of 11 scoliosis. In group with Risser grade 3 or above, with a single vertebral fracture and lumbar fracture, final regional Cobb angle was statistically higher than initial regional Cobb angle. CONCLUSIONS: The prevalence of scoliosis in our population is higher than those of idiopathic scoliosis; Risser grade 3 or above, lumbar fracture and a single fracture seem to account for more severe coronal deformatio

Conservative treatment of pediatric thoracic and lumbar spinal fractures

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

Les urétérostomies cutanées inguinales temporaires (bénéfices et controverses)

OBJECTIFS : Evaluer les bénéfices de l'urétérostomie cutanée dans la prise en charge temporaire des uropathies malformatives chez le petit enfant. PATIENTS ET METHODES : Etude rétrospective unicentrique de 18 dossiers (12 reflux vésico-urétéraux, dont 1 sur valves de l'urètre postérieur, et 6 mégauretères obstructifs) d'enfants suivis entre 1989 et 2011, qui présentaient des pyélonéphrites récidivantes malgré l'antibioprophylaxie, une incertitude sur la valeur fonctionnelle du rein sous-jacent ou l'association des deux conditions. RESULTATS : L'analyse des dossiers s'est faite en 5 points. L'urétérostomie : - diminue l'incidence des pyélonéphrites récidivantes, - ne permet pas une meilleure évaluation de la valeur fonctionnelle du rein sous-jacent, - ne diminue pas significativement le nombre de remodelages, - allonge la durée opératoire d'une réimplantation, - est relativement supportable pour la famille. CONCLUSION : L'urétérostomie est une technique utile dans la prévention des pyélonéphrites récidivantes du nourrisson quand l'antibioprophylaxie est insuffisante. C'est une dérivation bien supportée par la famille.OBJECTIVES : To evaluate cutaneous ureterostomy advantages in temporary treatment of malformative uropathies in young children. PATIENTS AND METHODS : Retrospective, unicentric analysis of 18 cases (12 vesico-ureteric reflux, of which 1 on posterior uretral valves, and 6 megaureters) followed between 1989 and 2011. Children were presenting recurrent urinary tract infections under antibioprophylaxis, doubtful functional value of the overlying kidney or both of the conditions. RESULTS : Analysis was conducted under 5 points. It shows that ureterostomy : - decreases recurrent pyelonephritis incidence, - does not allow a better evaluation of the overlying kidney function, - does not significantly decrease tailoring rate during reimplantation, - lengthens operative time of reimplantation, - is socially acceptable for parents. CONCLUSION : Ureterostomy can be a useful technique in preventing recurrent pyelonephritis in infant when antibioprophylaxis is insufficient. This is a well-tolerated urinary diversion for parents.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

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

International audienceAbstract 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. 1 H 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

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

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

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

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