Characterization of the Beckwith-Wiedemann spectrum: Diagnosis and management.

Beckwith-Wiedemann syndrome (BWS) is the most common epigenetic overgrowth and cancer predisposition disorder. Due to both varying molecular defects involving chromosome 11p15 and tissue mosaicism, patients can present with a variety of clinical features, leading to the newly defined Beckwith-Wiedemann spectrum (BWSp). The BWSp can be further divided into three subsets of patients: those presenting with classic features, those presenting with isolated lateralized overgrowth (ILO) and those not fitting into the previous two categories, termed atypical BWSp. Previous reports of patients with BWS have focused on those with the more recognizable, classic features, and limited information is available on those who fit into the atypical and ILO categories. Here, we present the first cohort of patients recruited across the entire BWSp, describe clinical features and molecular diagnostic characteristics, and provide insight into practical diagnosis and management recommendations that we have gained from this cohort.

Recent advancements in noninvasive brain modulation for individuals with autism spectrum disorder.

Autism spectrum disorder is classified as a spectrum of neurodevelopmental disorders with an unknown definitive etiology. Individuals with autism spectrum disorder show deficits in a variety of areas including cognition, memory, attention, emotion recognition, and social skills. With no definitive treatment or cure, the main interventions for individuals with autism spectrum disorder are based on behavioral modulations. Recently, noninvasive brain modulation techniques including repetitive transcranial magnetic stimulation, intermittent theta burst stimulation, continuous theta burst stimulation, and transcranial direct current stimulation have been studied for their therapeutic properties of modifying neuroplasticity, particularly in individuals with autism spectrum disorder. Preliminary evidence from small cohort studies, pilot studies, and clinical trials suggests that the various noninvasive brain stimulation techniques have therapeutic benefits for treating both behavioral and cognitive manifestations of autism spectrum disorder. However, little data is available for quantifying the clinical significance of these findings as well as the long-term outcomes of individuals with autism spectrum disorder who underwent transcranial stimulation. The objective of this review is to highlight the most recent advancements in the application of noninvasive brain modulation technology in individuals with autism spectrum disorder.

Characterization and Childhood Tumor Risk Assessment of Genetic and Epigenetic Syndromes Associated With Lateralized Overgrowth.

Lateralized overgrowth (LO), or segmental overgrowth, is defined as an increase in growth of tissue (bone, muscle, connective tissue, vasculature, etc.) in any region of the body. Some overgrowth syndromes, characterized by both generalized and lateralized overgrowth, have been associated with an increased risk of tumor development. This may be due to the underlying genetic and epigenetic defects that lead to disrupted cell growth and proliferation pathways resulting in the overgrowth and tumor phenotypes. This chapter focuses on the four most common syndromes characterized by LO: Beckwith-Wiedemann spectrum (BWSp), PIK3CA-related overgrowth spectrum (PROS), Proteus syndrome (PS), and PTEN hamartoma tumor syndrome (PHTS). These syndromes demonstrate variable risks for tumor development in patients affected by LO, and we provide a comprehensive literature review of all common tumors reported in patients diagnosed with an LO-related disorder. This review summarizes the current data on tumor risk among these disorders and their associated tumor screening guidelines. Furthermore, this chapter highlights the importance of an accurate diagnosis when a patient presents with LO as similar phenotypes are associated with different tumor risks, thereby altering preventative screening protocols.

The effectiveness of Wilms tumor screening in Beckwith-Wiedemann spectrum.

PURPOSE: It is well documented that patients with Beckwith-Wiedemann spectrum (BWS) have a significantly higher risk of developing Wilms tumor (WT) than the general population. There has been little research on the timing of WT diagnosis in BWS in regard to optimizing suggested screening protocols. METHODS: A literature search was performed to identify all reports of patients with BWS and WT. These data were combined with unpublished data from patients in the authors' cohorts. Age at WT diagnosis was compared against data collected through the NIH Surveillance, Epidemiology, and End Results Program (SEER) registry. RESULTS: Patients with BWS had a significantly higher incidence of WT diagnoses between age 12 and 84 months compared to patients in the SEER registry. Patients with BWS and WT diagnosed through screening had significantly lower stages at diagnosis compared to patients with BWS that were not screened. CONCLUSIONS: Screening until age 7 years is effective in detecting close to 95% of all WT in patients with BWS.