Disentangling the heterogeneity of autism spectrum disorder through genetic findings

Autism spectrum disorder (ASD) represents a heterogeneous group of disorders, which presents a substantial challenge to diagnosis and treatment. Over the past decade, considerable progress has been made in the identification of genetic risk factors for ASD that define specific mechanisms and pathways underlying the associated behavioural deficits. In this Review, we discuss how some of the latest advances in the genetics of ASD have facilitated parsing of the phenotypic heterogeneity of this disorder. We argue that only through such advances will we begin to define endophenotypes that can benefit from targeted, hypothesis-driven treatments. We review the latest technologies used to identify and characterize the genetics underlying ASD and then consider three themes—single-gene disorders, the gender bias in ASD, and the genetics of neurological comorbidities—that highlight ways in which we can use genetics to define the many phenotypes within the autism spectrum. We also present current clinical guidelines for genetic testing in ASD and their implications for prognosis and treatment

Prognostic Factors for Survival in Patients with High-Grade Meningioma and Recurrence-Risk Stratification for Application of Radiotherapy

Background: Radiotherapy for high-grade meningioma (HGM) is one of the essential treatment options for disease control. However, appropriate irradiation timing remains under debate. The object of this study is to discern which prognostic factors impact recurrence in HGM patients and to propose a risk-stratification system for the application of postoperative radiotherapy. Methods: We retrospectively reviewed 55 adult patients who were diagnosed with Grade II and III intracranial meningioma. Cox regression models were applied to the analysis for impact on early recurrence in HGM patients without postoperative radiotherapy. Results: Grade III malignancy (P = 0.0073) and transformed histology (P = 0.047) proved to be significantly poor prognostic factors of early recurrence by multivariate analysis. The other candidates for recurrence factors were Simpson Grade 3-5 resection, preoperative Karnofsky Performance status, = 15%. According to these prognostic factors, postoperative HGM patients could be stratified into three recurrence-risk groups. The prognoses were significantly different between each group, as the 3-year actual recurrence-free rates were 90% in low-risk group, 31% in intermediate-risk group, and 15% in high-risk group. Conclusion: We propose recurrence-risk stratification for postoperative HGM patients using clinically available factors. Our results suggest that the prognosis for patients with high-risk HGMs is dismal, whereas HGM patients belonging to the low-risk group could have favorable prognoses. This stratification provides us with the criteria necessary to determine whether to apply adjuvant radiotherapy to postoperative HGM patients, and to also help identify potentially curable HGMs without adjuvant radiotherapy