Observational studyThe Lancet. Child & adolescent health2025
Early childhood height, weight, and BMI development in children with monogenic obesity: a European multicentre, retrospective, observational study.
Observational study in The Lancet. Child & adolescent health, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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The trial behind it
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Who cites it
12 citing papers in PubMed.
- IMPROVE 2025: The 3rd International Meeting on Pathway-Related Obesity: Vision & Evidence.Clinical obesity · 2026Article
- Variants in the leptin-MC4R pathway and ciliopathy-related genes in youths with obesity beyond hyperphagia and early onset.Journal of endocrinological investigation · 2026Article
- Shared and distinct genetic architectures of eating disorders and obesity: From monogenic causes to polygenic risk.Reviews in endocrine & metabolic disorders · 2026Review
- Protein-truncating variants in APBA1 in minors with severe, early-onset obesity: implications for genetic testing.Molecular and cellular pediatrics · 2026Article
- Management of Childhood Obesity.International journal of molecular sciences · 2026Review
- The genetics of obesity: aetiology, prevention and therapy.Nature metabolism · 2026Review
- Exploring Autosomal Dominant Non-Syndromic Monogenic Obesity: From Genes to Therapy.Current issues in molecular biology · 2026Review
- Targeted Next-Generation Sequencing of the Leptin-Melanocortin Pathway in Severe Obesity.Obesity (Silver Spring, Md.) · 2026Article
- Monogenic obesity due to MC4R deficiency: lessons from a multigenerational case.Molecular and cellular pediatrics · 2026Article
- Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan.Journal of endocrinological investigation · 2025Review
- BMI profiling for monogenic obesity testing.The Lancet. Child & adolescent health · 2025Article
- Evaluating the role of insulin resistance in chronic intestinal health issues: NHANES study findings.Frontiers in nutrition · 2025Article
Corrections and comments
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Authors and funding
21 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMonogenic 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.
methodsThis 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.
findingsWe 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% female vs 47% male) and control children (n=113, 59% female vs 41% male). Children with biallelic LEP, LEPR, and MC4R variants showed a steep BMI increase during the first year of life, followed by a plateau until age 5 years, whereas those with biallelic POMC variants did not plateau. Accelerated linear growth was only observed in children with biallelic MC4R variants starting from age 1 year. The optimal BMI cut-off for distinguishing individuals with biallelic variants from control individuals was identified at age 2 years, with a test positivity cutoff of 24·0 kg/m
interpretationThis study identified characteristic early childhood BMI trajectories for different forms of monogenic obesity. From age 6 months onwards, individuals with biallelic variants can be distinguished from those with monoallelic variants and common obesity. A BMI ≥24 kg/m
fundingFederal Ministry of Education and Research as part of the German Center for Child and Adolescent Health, German Research Foundation, Spanish Ministry of Health, The Wellcome Trust, Botnar Fondation, Leducq Foundation, National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, and NIHR Senior Investigator Award.
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