Molecular Basis and Diagnostic Approach to Isolated and Syndromic Lateralized Overgrowth in Childhood.

Objective: To demonstrate a high-yield molecular diagnostic workflow for lateralized overgrowth (LO), a congenital condition with abnormal enlargement of body parts, and to classify it by molecular genetics.

Study Design: We categorized 186 retrospective cases of LO diagnosed between 2003 and 2023 into suspected Beckwith-Wiedemann spectrum, PIK3CA-related overgrowth spectrum (PROS), vascular overgrowth, or isolated LO, based on initial clinical assessments, to determine the appropriate first-tier molecular tests and tissue for analysis. Patients underwent testing for 11p15 epigenetic abnormalities or somatic variants in genes related to PI3K/AKT/mTOR, vascular proliferation, and RAS-MAPK cascades using blood or skin DNA.

Work-Up and Treatment Strategies for Individuals with -Related Disorders: A Consensus of Experts from the Scientific Committee of the Italian Macrodactyly and PROS Association.

-related disorders encompass many rare and ultra-rare conditions caused by somatic genetic variants that hyperactivate the PI3K-AKT-mTOR signaling pathway, which is essential for cell cycle control. -related disorders include -related overgrowth spectrum (PROS), -related vascular malformations and -related non-vascular lesions. Phenotypes are extremely heterogeneous and overlapping.

Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer.

Breast cancer (BC) is the most common cancer and the leading cause of cancer death in women worldwide. Since the discovery of the highly penetrant susceptibility genes and , many other predisposition genes that confer a moderate risk of BC have been identified. Advances in multigene panel testing have allowed the simultaneous sequencing of with these genes in a cost-effective way.

Total serum FGF-21 levels positively relate to visceral adiposity differently from its functional intact form.

Objective: Increased Fibroblast Growth Factor-21 (FGF-21) circulating levels have been described in obesity. In this observational study, we analysed a group of subjects with metabolic disorders to unravel the putative link between visceral adiposity and FGF-21 serum levels.

Methods: Total and intact serum FGF-21 concentration was measured with an ELISA assay respectively in 51 and 46 subjects, comparing FGF-21 levels in dysmetabolic conditions.

The somatic p.T81dup variant in AKT3 gene underlies a mild cerebral phenotype and expands the spectrum including capillary malformation and lateralized overgrowth.

Heterozygous germline or somatic variants in AKT3 gene can cause isolated malformations of cortical development (MCDs) such as focal cortical dysplasia, megalencephaly (MEG), Hemimegalencephaly (HME), dysplastic megalencephaly, and syndromic forms like megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome, and megalencephaly-capillary malformation syndrome. This report describes a new case of HME and capillary malformation caused by a somatic AKT3 variant that differs from the common p.E17K variant described in literature.