title: Melanocortin-4 Receptor Deficiency Phenotype with an Interstitial 18q Deletion: A Case Report of Severe Childhood Obesity and Tall Stature.
abstract: Childhood obesity is a growing health concern, associated with significant physical and psychological morbidity. Childhood obesity is known to have a strong genetic component, with mutations in themelanocortin-4 receptor(MC4R) gene being the most common monogenetic cause of obesity. Over 166 differentMC4Rmutations have been identified in persons with hyperphagia, severe childhood obesity, and increased linear growth. However, it is unclear whether the MC4-R deficiency phenotype is due to haploinsufficiency or dominant-negative effects by the mutant receptor. We report the case of a four-and-a-half-year-old boy with an interstitial deletion involving the long arm of chromosome 18 (46,XY,del(18)(q21.32q22.1)) encompassing theMC4Rgene. This patient presented with tall stature and hyperphagia within his first 18 months of life leading to significant obesity. This case supports haploinsufficiency of MC4-R as it describes a MC4-R deficiency phenotype in a patient heterozygous for a fullMC4Rgene deletion. The intact functional allele with MC4-R haploinsufficiency has the potential to favor a therapeutic response to gastric surgery. Currently, small molecule MC4-R agonists are under development for pharmacologic therapy.
authors.affiliation: School of Medicine, Queen's University, Kingston, ON, Canada.
authors.forename: Sarah
authors.identifier: 0000-0002-9721-3250
authors.initials: S
authors.lastname: Abdullah
authors.affiliation: Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.
authors.forename: William
authors.identifier: 0000-0001-5325-7561
authors.initials: W
authors.lastname: Reginold
authors.affiliation: Department of Pediatrics, Kingston General Hospital, Kingston, ON, Canada.
authors.forename: Courtney
authors.identifier: 0000-0002-7561-8556
authors.initials: C
authors.lastname: Kiss
authors.affiliation: Department of Pathology and Laboratory Medicine, IWK Health Centre, Halifax, NS, Canada; Department of Pathology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Harrison
authors.affiliation: School of Medicine, Queen's University, Kingston, ON, Canada; Department of Pediatrics, Kingston General Hospital, Kingston, ON, Canada.
authors.forename: Jennifer J
authors.identifier: 0000-0002-3374-8619
authors.initials: JJ
authors.lastname: MacKenzie