IMPORTANCE Whole-exome sequencing (WES) has the potential to reveal tumor and germline mutations of clinical relevance, but the diagnostic yield for pediatric patients with solid tumors is unknown. OBJECTIVE To characterize the diagnostic yield of combined tumor and germline WES for children with solid tumors. DESIGN Unselected children with newly diagnosed and previously untreated central nervous system (CNS) and non-CNS solid tumors were prospectively enrolled in the BASIC3 study at a large academic children’s hospital during a 23-month period from August 2012 through June 2014. Blood and tumor samples underwent WES in a certified clinical laboratory with genetic results categorized on the basis of perceived clinical relevance and entered in the electronic health record. MAIN OUTCOMES AND MEASURES Clinical categorization of somatic mutations; frequencies of deleterious germline mutations related to patient phenotype and incidental medically-actionable mutations. RESULTS Of the first 150 participants (80 boys and 70 girls, mean age, 7.4 years), tumor samples adequate for WES were available from 121 patients (81%). Somatic mutations of established clinical utility (category I) were reported in 4 (3%) of 121 patients, with mutations of potential utility (category II) detected in an additional 29 (24%) of 121 patients. CTNNB1 was the gene most frequently mutated, with recurrent mutations in KIT, TSC2, and MAPK pathway genes (BRAF, KRAS, and NRAS) also identified. Mutations in consensus cancer genes (category III) were found in an additional 24 (20%) of 121 tumors. Fewer than half of somatic mutations identified were in genes known to be recurrently mutated in the tumor type tested. Diagnostic germline findings related to patient phenotype were discovered in 15 (10%) of 150 cases: 13 pathogenic or likely pathogenic dominant mutations in adult and pediatric cancer susceptibility genes (including 2 each in TP53, VHL, and BRCA1), 1 recessive liver disorder with hepatocellular carcinoma (TJP2), and 1 renal diagnosis (CLCN5). Incidental findings were reported in 8 (5%) of 150 patients. Most patients harbored germline uncertain variants in cancer genes (98%), pharmacogenetic variants (89%), and recessive carrier mutations (85%). CONCLUSIONS AND RELEVANCE Tumor and germline WES revealed mutations in a broad spectrum of genes previously implicated in both adult and pediatric cancers. Combined reporting of tumor and germline WES identified diagnostic and/or potentially actionable findings in nearly 40% of newly diagnosed pediatric patients with solid tumors.

BackgroundSacrectomy remains a technically complex procedure for resection of malignant pelvic neoplasia. Commonly, postoperative complications include permanent neurological deficits. Only a few studies have reported the long-term functional outcomes of patients who had undergone sacrectomy.Case presentationWe previously reported on the utilization of complete sacrectomy and lumbopelvic reconstruction for the management of primary myofibroblastic sarcoma of the sacrum and ilium in a 15-year-old female patient. In this report, we update her postoperative course with an additional 5 years of follow-up and Health-Related Quality of Life (HRQoL) outcomes. During this time period, she gave birth to two healthy full-term babies.ConclusionTo the best of our knowledge, this is the first report of pregnancy after total sacrectomy and lumbopelvic reconstruction. We outline some of the challenges in the obstetrical management of this patient.

Object Cephaloceles represent primary axial mesodermal defects, occurring in 0.8–4 per 10,000 live births. Prior studies have reported posterior location, hydrocephalus, microcephaly, seizure, and presence of brain tissue as poor prognostic markers for neurological outcome. However, these studies were small and the results were analyzed using univariate tests. The purpose of this study was to investigate the potential risk factors for the occurrence of developmental delay in patients with cephaloceles, using both univariate and multivariable regression techniques. Methods This is a retrospective cohort study of cephalocele cases treated at the Hospital for Sick Children between 1990 and 2006. Two independent investigators collected the data from the Hospital for Sick Children Encephalocele Database and hospital charts. Developmental assessments were made by general pediatricians and neuropsychologists. Both univariate analysis (α = 0.10) and multivariable logistic regression analysis (α = 0.05) were performed. Results Eighty-five cases of cephaloceles were identified. The patient group consisted of 48 boys and 37 girls. Sixty-eight lesions were encephaloceles and 17 were meningoceles. The distribution was as follows: frontal (40 lesions), occipital (33), and parietal (12). Associated conditions included hydrocephalus (23), seizure disorder (17), microcephaly (6), corpus callosal abnormalities (15), heterotopias (9), cerebral dysgenesis (11), and myelomeningocele (1). Evaluation of long-term development revealed that 41 patients (48%) had normal development, 9 (11%) had mild delay, 14 (16%) had moderate delay, and 21 (25%) had severe delay. Hydrocephalus, seizure disorder, microcephaly, presence of associated intracranial abnormalities, and presence of brain tissue were significantly associated with poor outcome on univariate analysis. Multivariable analysis revealed hydrocephalus and presence of intracranial abnormalities to be statistically significant predictors of developmental delay. Conclusions To the authors' knowledge, this is one of the largest North American cephalocele series documented. Unlike prior studies, location of the cephaloceles is not a significant predictor of outcome. The multivariable regression analysis demonstrates hydrocephalus and the presence of associated intracranial abnormalities as variables with cumulative predictive effects for developmental delay.