{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:58:04Z","timestamp":1770141484101,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this study was to investigate head circumference (HC) in patients with melanocortin 4 receptor (MC4R) deficiency, the most common cause of monogenetic obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with (likely) pathogenic <jats:italic>MC4R<\/jats:italic> variants were included. HC, height, and weight were measured, and BMI and standard deviation score (SDS) were calculated. HC SDS was compared to the Dutch reference population. Children were matched 1:1 to a control group with common obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Children with MC4R deficiency (<jats:italic>n<\/jats:italic>\u2009=\u200963, mean age, 10.32\u2009years) had significantly larger HC (mean,\u2009+1.73 SDS) compared to the reference population (0 SDS; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and controls (+1.22 SDS; <jats:italic>p<\/jats:italic>\u2009=\u20090.009). In adults (<jats:italic>n<\/jats:italic>\u2009=\u200913), HC (median,\u2009+\u20090.86 SDS) did not differ from the reference population (0 SDS; <jats:italic>p<\/jats:italic>\u2009=\u20090.152). Macrocephaly (HC\u2009\u2265\u20092 SDS) was present in 43%, 25%, and 23% of pediatric patients with MC4R deficiency, controls, and adult patients, respectively. Children with MC4R deficiency were taller than controls (+1.00 SDS vs. +0.42 SDS; <jats:italic>p<\/jats:italic>\u2009=\u20090.016), with similar BMI (+3.99 SDS vs. +3.75 SDS; <jats:italic>p<\/jats:italic>\u2009=\u20090.157). HC SDS was associated with height SDS (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>, 0.22; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and homeostatic model assessment of insulin resistance (correlation coefficient, 0.542; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Macrocephaly is a common feature of patients with MC4R deficiency. We recommend measuring HC in patients suspected for genetic obesity, as it can be a clue for MC4R deficiency.<\/jats:p><\/jats:sec>","DOI":"10.1002\/oby.24263","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T09:40:46Z","timestamp":1744710046000},"page":"986-995","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unraveling the relationship between head circumference and <scp>MC4R<\/scp> deficiency from infancy to adulthood: a case\u2013control study"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7789-7627","authenticated-orcid":false,"given":"Eline E. P. L.","family":"van der Walle","sequence":"first","affiliation":[{"name":"Obesity Center Centrum Gezond Gewicht (CGG), Erasmus Medical Center University Medical Center Rotterdam  Rotterdam The Netherlands"},{"name":"Center of Expertise for Genetic Obesity Erasmus Medical Center and Amsterdam University Medical Center  Amsterdam The Netherlands"},{"name":"Department of Pediatrics, Division of Pediatric Endocrinology Erasmus University Medical Center\u2010Sophia Children's Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelis J.","family":"de Groot","sequence":"additional","affiliation":[{"name":"Obesity Center Centrum Gezond Gewicht (CGG), Erasmus Medical Center University Medical Center Rotterdam  Rotterdam The Netherlands"},{"name":"Center of Expertise for Genetic Obesity Erasmus Medical Center and Amsterdam University Medical Center  Amsterdam The Netherlands"},{"name":"Department of Pediatrics IJsselland Hospital  Capelle aan den Ijssel The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lotte","family":"Kleinendorst","sequence":"additional","affiliation":[{"name":"Center of Expertise for Genetic Obesity Erasmus Medical Center and Amsterdam University Medical Center  Amsterdam The Netherlands"},{"name":"Department of Human Genetics, Amsterdam Reproduction and Development Research Institute, Amsterdam University Medical Center University of Amsterdam  Amsterdam The Netherlands"},{"name":"Emma Center for Personalized Medicine Amsterdam University Medical Center  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hester","family":"de Klerk","sequence":"additional","affiliation":[{"name":"Obesity Center Centrum Gezond Gewicht (CGG), Erasmus Medical Center University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9261-5541","authenticated-orcid":false,"given":"Mila S.","family":"Welling","sequence":"additional","affiliation":[{"name":"Obesity Center Centrum Gezond Gewicht (CGG), Erasmus Medical Center University Medical Center Rotterdam  Rotterdam The Netherlands"},{"name":"Center of Expertise for Genetic Obesity Erasmus Medical Center and Amsterdam University Medical Center  Amsterdam The Netherlands"},{"name":"Department of Pediatrics, Division of Pediatric Endocrinology Erasmus University Medical Center\u2010Sophia Children's Hospital  Rotterdam The Netherlands"},{"name":"Department of Internal Medicine, Division of Endocrinology Erasmus Medical Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1343-6562","authenticated-orcid":false,"given":"Ozair","family":"Abawi","sequence":"additional","affiliation":[{"name":"Obesity Center Centrum Gezond Gewicht (CGG), Erasmus Medical Center University Medical Center Rotterdam  Rotterdam The Netherlands"},{"name":"Center of Expertise for Genetic Obesity Erasmus Medical Center and Amsterdam University Medical Center  Amsterdam The Netherlands"},{"name":"Department of Pediatrics, Division of Pediatric Endocrinology Erasmus University Medical Center\u2010Sophia Children's Hospital  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renate E. H.","family":"Meeusen","sequence":"additional","affiliation":[{"name":"Obesity Center Centrum Gezond Gewicht (CGG), Erasmus Medical Center University Medical Center Rotterdam  Rotterdam The Netherlands"},{"name":"Department of Internal Medicine, Division of Endocrinology Erasmus Medical Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari\u00ebtte R.","family":"Boon","sequence":"additional","affiliation":[{"name":"Obesity Center Centrum Gezond Gewicht (CGG), Erasmus Medical Center University Medical Center Rotterdam  Rotterdam The Netherlands"},{"name":"Center of Expertise for Genetic Obesity Erasmus Medical Center and Amsterdam University Medical Center  Amsterdam The Netherlands"},{"name":"Department of Pediatrics, Division of Pediatric Endocrinology Erasmus University Medical Center\u2010Sophia Children's Hospital  Rotterdam The Netherlands"},{"name":"Department of Internal Medicine, Division of Endocrinology Erasmus Medical Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0120-4913","authenticated-orcid":false,"given":"Elisabeth F. 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