Early childhood height, weight, and BMI development in children with monogenic obesity: a European multicentre, retrospective, observational study

作者：Stefanie Zorn, C. Groot, Stephanie Brandt-Heunemann, Julia von Schnurbein, Ozair Abawi, Rebecca Bounds, Lisa Rück, Blanca Guijo, Gabriel Ángel Martos‐Moreno, Clarisse Nicaise, Sophie Courbage, Margit Klehr-Martinelli, Reiner Siebert, B. Dubern, Christine Poitou, Karine Clément, Jesús Argente, Peter Kühnen, I. Sadaf Farooqi, Martin Wabitsch, Erica L T van den Akker · 发表于：The Lancet Child & Adolescent Health · 年份：2025 · DOI：10.1016/s2352-4642(25)00065-3 · 被引用次数：17 · 研究领域：Regulation of Appetite and Obesity、Genetic Associations and Epidemiology、Pancreatic function and diabetes

Background Monogenic defects in the leptin-melanocortin pathway are associated with hyperphagia and severe, early-onset obesity. Early childhood growth patterns in height, weight, and BMI, might serve as phenotypic markers for specific genetic disorders; however, reliable data are scarce. This study aimed to evaluate the natural history of height, weight, and BMI in early childhood in a large European group of individuals with monogenic obesity. Methods This multicentre observational study analysed height, weight, and BMI from birth to age 5 years in individuals diagnosed with biallelic (likely) pathogenic LEP, LEPR, POMC, PCSK1, or MC4R variants or monoallelic (likely) pathogenic MC4R variants from six European centres (Berlin and Ulm, Germany; Cambridge, UK; Madrid, Spain; Paris, France; Rotterdam, Netherlands). All patient data up to May 31, 2022 were included in this analysis. All individuals had at least two height or weight measurements between birth and age 5 years. Early childhood growth trajectories were compared with those of control children with obesity without a known genetic cause, following a negative next-generation sequencing panel. Diagnostic performance of BMI as a predictor test for monogenic obesity was also evaluated. Findings We included 147 individuals with monogenic obesity. From the age of 6 months onwards, children with biallelic variants (n=88, 55% female vs 45% male) had substantially higher BMIs than those with monoallelic MC4R variants (n=59, 53...