Peripheral Vascular Emboli in Patients with Infective Endocarditis are Common.

Objective: Infective endocarditis (IE) is associated with significant morbidity and mortality and places patients at risk for subsequent peripheral vascular emboli. Our goals were to analyze the incidence of peripheral emboli and their associated complications and outcomes.

Methods: A retrospective single-center review of all patients with IE from 2013-2021 was performed.

Extrauterine support of pre-term lambs achieves similar transcriptomic profiling to late pre-term lamb brains.

Our group has developed an extra-uterine environment for newborn development (EXTEND) using an ovine model, that aims to mimic the womb to improve short and long-term health outcomes associated with prematurity. This study's objective was to determine the histologic and transcriptomic consequences of EXTEND on the brain. Histology and RNA-sequencing was conducted on brain tissue from three cohorts of lambs: control pre-term (106-107 days), control late pre-term (127 days), and EXTEND lambs who were born pre-term and supported on EXTEND until late pre-term age (125-128 days).

Update on Surveillance Guidelines in Emerging Wilms Tumor Predisposition Syndromes.

Wilms tumors are commonly associated with predisposition syndromes. Many of these syndromes are associated with specific phenotypic features and are discussed in the related article from the AACR Pediatric Cancer Working Group. Guidelines for surveillance in this population were published in 2017, but since then several studies have identified new genes with recurrent pathogenic variants associated with increased risk for Wilms tumor development.

Morphometric measurements of intraoral anatomy in children with Beckwith-Wiedemann syndrome: a novel approach.

Background: An easy-to-use tool to objectively measure intraoral anatomy with meaningful clinical correlations may improve care for patients with Beckwith-Wiedemann syndrome (BWS), who commonly have symptomatic macroglossia.

Methods: Children aged 2-17 years with BWS were enrolled between 12/2021 and 01/2024. Digital intraoral photographs with a laser ruler were taken, and morphometric measurements were made using ImageJ software.

The Peripheral Reduction With Keyhole Tongue Reduction Technique for Macroglossia in Beckwith-Wiedemann Syndrome.

Objective: Patients with Beckwith-Wiedemann syndrome commonly have macroglossia, which can negatively affect dentoskeletal development, breathing, speaking, and eating. Tongue reduction surgery can improve symptoms, but there is no standardized surgical approach.

Methods: A video and observational commentary highlighting the effectiveness of a tongue reduction technique for BWS were presented.

Phenotypic spectrum and tumor risk in Simpson-Golabi-Behmel syndrome: Case series and comprehensive literature review.

Simpson-Golabi-Behmel syndrome (SGBS) is a rare congenital overgrowth condition characterized by macrosomia, macroglossia, coarse facial features, and development delays. It is caused by pathogenic variants in the GPC3 gene on chromosome Xq26.2.

Multi-locus imprinting disturbance (MLID): interim joint statement for clinical and molecular diagnosis.

Background: Imprinting disorders are rare diseases resulting from altered expression of imprinted genes, which exhibit parent-of-origin-specific expression patterns regulated through differential DNA methylation. A subgroup of patients with imprinting disorders have DNA methylation changes at multiple imprinted loci, a condition referred to as multi-locus imprinting disturbance (MLID). MLID is recognised in most but not all imprinting disorders and is also found in individuals with atypical clinical features; the presence of MLID often alters the management or prognosis of the affected person.

Single-nucleus multiomic analysis of Beckwith-Wiedemann syndrome liver reveals PPARA signaling enrichment and metabolic dysfunction.

Beckwith-Wiedemann Syndrome (BWS) is an epigenetic overgrowth syndrome caused by methylation changes in the human 11p15 chromosomal locus. Patients with BWS exhibit tissue overgrowth, as well as an increased risk of childhood neoplasms in the liver and kidney. To understand the impact of these 11p15 changes, specifically in the liver, we performed single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin with sequencing (snATAC-seq) to generate paired, cell-type-specific transcriptional and chromatin accessibility profiles of both BWS-liver and nonBWS-liver nontumorous tissue.

Clinical Updates and Surveillance Recommendations for DNA Replication Repair Deficiency Syndromes in Children and Young Adults.

Replication repair deficiency (RRD) is a pan-cancer mechanism characterized by abnormalities in the DNA mismatch repair (MMR) system due to pathogenic variants in the PMS2, MSH6, MSH2, or MLH1 genes, and/or in the polymerase-proofreading genes POLE and POLD1. RRD predisposition syndromes (constitutional MMR deficiency, Lynch, and polymerase proofreading-associated polyposis) share overlapping phenotypic and biological characteristics. Moreover, cancers stemming from germline defects of one mechanism can acquire somatic defects in another, leading to complete RRD.

Expanded phenotype and cancer risk in patients with Beckwith-Wiedemann spectrum caused by CDKN1C variants.

Beckwith-Wiedemann spectrum (BWSp) is caused by genetic and epigenetic alterations on chromosome 11 that regulate cell growth and division. Considering the diverse phenotypic landscape in BWSp, the characterization of the CDKN1C molecular subtype remains relatively limited. Here, we investigate the role of CDKN1C in the broader BWSp phenotype.

Retrieval of Embolized WATCHMAN Flex Atrial Appendage Occlusion Device.

This case report documents the management of a 66-year old man with atrial fibrillation with recent placement of a WATCHMAN Flex atrial appendage occlusion device. The patient presented with renal failure, abdominal pain, and difficulty walking 2 months after placement. The WATCHMAN Flex device was found to have embolized to his abdominal aorta at the level of the renal arteries with associated thrombus.

GestaltMML: Enhancing Rare Genetic Disease Diagnosis through Multimodal Machine Learning Combining Facial Images and Clinical Texts.

Individuals with suspected rare genetic disorders often undergo multiple clinical evaluations, imaging studies, laboratory tests and genetic tests, to find a possible answer over a prolonged period of time. Addressing this "diagnostic odyssey" thus has substantial clinical, psychosocial, and economic benefits. Many rare genetic diseases have distinctive facial features, which can be used by artificial intelligence algorithms to facilitate clinical diagnosis, in prioritizing candidate diseases to be further examined by lab tests or genetic assays, or in helping the phenotype-driven reinterpretation of genome/exome sequencing data.

A Novel Macroglossia Severity Index for Beckwith-Wiedemann Syndrome.

Objective/ Summary Background Data: We propose the first classification scheme for macroglossia in patients with Beckwith-Wiedemann Syndrome (BWS), the BWS Index of macroGlossia (BIG).

Methods: Patients with molecularly confirmed BWS seen from 2004-2023 were included to develop this system. Relationships among BIG scores, tongue reduction surgery, BWS clinical score, percent mosaicism, and polysomnography findings were examined.

Cancer predisposition signaling in Beckwith-Wiedemann Syndrome drives Wilms tumor development.

Background: Wilms tumor (WT) exhibits structural and epigenetic changes at chromosome 11p15, which also cause Beckwith-Wiedemann Syndrome (BWS). Children diagnosed with BWS have increased risk for WT. The aim of this study is to identify the molecular signaling signatures in BWS driving these tumors.

Introduction to the Beckwith-Wiedemann Syndrome and Cancer Special Issue.

Beckwith-Wiedemann syndrome (BWS) is a genetic imprinting disorder that most commonly presents as overgrowth, macroglossia, abdominal wall defects, lateralized overgrowth, and embryonal tumors [...

(Epi)genotype and Timing of Tongue Reduction Predict Safety and Long-Term Outcomes in Beckwith-Wiedemann Syndrome.

Background: Macroglossia is a cardinal feature of Beckwith-Wiedemann syndrome (BWS) with a clinical spectrum where the indication and timing for surgery remain to be validated. This study leverages a cohort of molecularly characterized patients with BWS to correlate epigenetic diagnosis with phenotype and treatment outcome.

Methods: Patients with BWS seen in consultation for macroglossia from 2009 to 2022 were reviewed for phenotype, molecular diagnosis, tongue reduction status, timing of surgery (early, less than 12 months), and perioperative complications.

Overgrowth syndromes, diagnosis and management.

Purpose Of Review: This review will focus on the current knowledge of the diagnosis and management of overgrowth syndromes with specific focus on mosaic conditions and treatment strategies.

Recent Findings: With the implementation of massively parallel sequencing, the genetic etiology of many classically described overgrowth syndromes have been identified. More recently, the role of mosaic genetic changes has been well described in numerous syndromes.