Clinical heterogeneity in children with gonadal dysgenesis associated with non-mosaic 46,XY karyotype.

INTRODUCTION: Gonadal dysgenesis is unique in disorders of sex development (DSD), in that it can be associated with 46,XX, 46,XY or mosaic 45,X/46,XY karyotypes. Gonadal dysgenesis can be partial or complete. Gonadal dysgenesis associated with the Y-chromosome has increased risk of gonadal germ cell neoplasms. Most of the literature focus on 45,X/46,XY gonadal dysgenesis, while there are scanty data on the condition when the karyotype is non-mosaic 46,XY. OBJECTIVE: To investigate the diversity of clinical pictures of children presenting with 46,XY DSD due to gonadal dysgenesis. METHODS: A retrospective study on consecutive patients diagnosed with 46,XY gonadal dysgenesis at age ≤18 years in a tertiary center from 1985 to 2015. The clinical presentations, phenotypes, gonadal features and associated anomalies were investigated. RESULTS: Twenty-eight patients with Y-chromosome gonadal dysgenesis were identified during the study period and six (21.4%) had non-mosaic 46,XY karyotype. Three had complete gonadal dysgenesis (CGD) with normal female phenotype, while the other three had partial gonadal dysgenesis (PGD). Of the three patients with CGD, two presented with the classical Swyer syndrome at adolescence, while the third presented at birth with multiple congenital anomalies. The three PGD patients presented with ambiguous genitalia at birth (n = 2), and isolated hypospadias (n = 1), which was associated with Frasier syndrome. Three patients had germ cell neoplasms: bilateral gonadoblastoma (n = 1), bilateral intratubular germ cell neoplasia unclassified (n = 1), and dysgerminoma + gonadoblastoma (n = 1). Two patients had global developmental delay with other congenital anomalies, and another patient had learning difficulties with borderline intelligence (Table). DISCUSSION: The findings suggest that 46,XY gonadal dysgenesis is much rarer than 45,X/46,XY gonadal dysgenesis. Patients differed in their clinical presentations and well-established syndromes happened in half of them. Overall, the risk of germ cell neoplasms and the association with other somatic anomalies appeared to be high. The study was limited by: its small number, single-center experience, and the possibility of missing the diagnosis in some male patients with mild undervirilization. CONCLUSION: Heterogeneity was noted in the clinical, phenotypic and gonadal features among pediatric patients with 46,XY gonadal dysgenesis.

The clip and drop back technique in the management of multifocal necrotizing enterocolitis: a single centre experience.

AIM: The surgical management of multifocal necrotizing enterocolitis (NEC) remains a major challenge. The "clip-and-drop" strategy with a second-look laparotomy permits re-assessment of bowel viability after optimization, thus offering the potential of both improving survival and conserving bowel length. This study reviews the outcome of this strategy in a single regional center. METHODS: Since 2000, NEC patients undergoing emergency laparotomy selectively underwent a "clip-and-drop" operation if there was peri-operative instability and/or multifocal disease with uncertain bowel viability. Bowel with full thickness gangrene was resected and bowel-ends were temporarily tied-off; a second-look definitive procedure was performed when the patient had stabilized. For this review, in-hospital and follow-up records were studied retrospectively for demographics, 30-day mortality and long-term outcome. MAIN RESULTS: Between 2000 and 2010, 16 patients underwent a "clip-and-drop" operation. The mean post-conception age was 32.8 weeks (27.7-41.7 weeks) with a median body weight of 1.4 kg (0.76-4.4 kg) at first operation. Preoperative radiograph showed free gas in 43.8% and portal venous gas in 37.5% of patients. 2 patients did not survive to the second laparotomy. 14 patients received a second laparotomy, after a mean of 51 h (35-74 h). 2 patients were found to suffer from NEC totalis on the second laparotomy and died without further procedures. All other patients (n = 12) had stoma formation. 1 patient died 4 days after stoma formation. The 30-day mortality for NEC with the "clip-and-drop" strategy was 31.6% (5/16). Among the 11 survivors, 1 died from liver failure complicated by short bowel syndrome at 5 months post operation, 2 others died from respiratory complications of prematurity despite adequate gastrointestinal function. The median follow-up time for the 8 long-term survivors was 45 months (7-129 months). Their median time to achieving full feeds was 41 days (range 21-105 days) after the second operation. CONCLUSION: The "clip-and-drop" strategy, when used in selected patients with multifocal NEC, may help bowel conservation in survivors.