{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:17:34Z","timestamp":1787919454312,"version":"build-2784847793"},"reference-count":82,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Investigation"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Obesity is increasingly being recognized as a heterogeneous condition with strong genetic underpinnings. Monogenic obesity, caused by single\u2010gene mutations, primarily affects the leptin\u2013melanocortin pathway, which regulates hunger and satiety. Mutations in genes, such as\n                    <jats:italic>LEP<\/jats:italic>\n                    ,\n                    <jats:italic>LEPR<\/jats:italic>\n                    ,\n                    <jats:italic>POMC<\/jats:italic>\n                    ,\n                    <jats:italic>PCSK1<\/jats:italic>\n                    , and\n                    <jats:italic>MC4R<\/jats:italic>\n                    , lead to hyperphagia, early onset severe obesity, and metabolic dysregulation.\n                    <jats:italic>LEP<\/jats:italic>\n                    and\n                    <jats:italic>LEPR<\/jats:italic>\n                    mutations impair leptin signaling, resulting in defective appetite suppression, whereas\n                    <jats:italic>POMC<\/jats:italic>\n                    and\n                    <jats:italic>PCSK1<\/jats:italic>\n                    deficiencies disrupt prohormone processing.\n                    <jats:italic>MC4R<\/jats:italic>\n                    mutations, the most common cause of monogenic obesity, impair satiety signaling and are linked to rapid weight gain. Syndromic obesity, including the Bardet\u2010Biedl and Alstr\u00f6m syndromes, involves ciliary dysfunction, leading to developmental abnormalities alongside obesity. Other genes such as\n                    <jats:italic>SH2B1<\/jats:italic>\n                    ,\n                    <jats:italic>SIM1<\/jats:italic>\n                    , and\n                    <jats:italic>BDNF<\/jats:italic>\n                    play crucial roles in hypothalamic development and energy regulation. Advances in genomic sequencing have improved the recognition of genetic etiologies; however, many patients remain undiagnosed due to limited testing availability and a lack of clinician awareness. Precision therapies, including set\u2010melanotide for specific melanocortin pathway defects, demonstrate the promise of targeted treatments. However, management must extend beyond pharmacology; lifestyle interventions, psychosocial support, and family\u2010centered care remain essential, especially when intellectual disability or behavioral challenges complicate adherence. Ethical considerations surrounding access and equity are critical, as high\u2010cost therapies and the limited availability of genetic testing risk widening disparities between health systems. Polygenic risk scores and multi\u2010omics approaches may expand precision medicine beyond rare genetic syndromes to common obesity, highlighting the importance of integrating genetics, psychosocial care, and policy advocacy in the management of pediatric obesity.\n                  <\/jats:p>","DOI":"10.1002\/ped4.70040","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T07:31:59Z","timestamp":1770708719000},"page":"333-344","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Monogenic and syndromic obesity in children: Clinical recognition, genetics, and precision management"],"prefix":"10.1002","volume":"10","author":[{"given":"Hadel","family":"Khalil","sequence":"first","affiliation":[{"name":"Maccabi Healthcare Services  Tel Aviv\u2010Yafo Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Feigin","sequence":"additional","affiliation":[{"name":"Department of internal medicine Diabetes Division University of Texas Health Science Center at San Antonio and Texas Diabetes Institute  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4979-3799","authenticated-orcid":false,"given":"Hussein","family":"Zaitoon","sequence":"additional","affiliation":[{"name":"Department of internal medicine Diabetes Division University of Texas Health Science Center at San Antonio and Texas Diabetes Institute  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003198"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1025635913927"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2012.00029"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16040539"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41366\u2010022\u201001139\u20107"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101206"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE\u201018\u20100596"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.10.021"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI142064"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2020.05.006"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/43185"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad099"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.722441"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02741"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00147"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40348\u2010021\u201000119\u20107"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa063988"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(20)30364\u20108"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1043\u20102760(99)00213\u20101"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.689387"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1512693"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.04.005"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.03.048"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165835"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI165418"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2011140118"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI142064"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010\u20101369"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154\u2010023\u201009804\u20106"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.24287"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.155900"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.2337\/db19\u20100608"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2022.01.018"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576\u2010021\u201000414\u2010z"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010017\u20100023\u20106"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0803390"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010\u20101733"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.0b013e31822bead0"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.1003\u20109406.2013.05.013"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1159\/000357054"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0b013e32835a255c"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.2147\/TACG.S56612"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920\u2010021\u201000929\u20108"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0801119"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13020335"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2024.1431400"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006957"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.09.011"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1086\/518047"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.13810"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.028"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010025\u201003827\u2010z"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.051"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE\u201020\u20100363"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1159\/000445061"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010022\u201002059\u20108"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2008.422"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00592\u2010023\u201002109\u20109"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2032183"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1916038"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac549"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/children12111427"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2207442"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(22)00277\u20107"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14133"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892\u2010020\u201001327\u20107"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2022\u2010060640"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016\u20102573"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.11809"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1542\/PEDS.2019\u20103224"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2021.08.678"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11695\u2010023\u201006593\u20104"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2404054"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnab034"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.25.14804"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.01387"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1080\/15374416.2023.2251164"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887\u2010020\u201002145\u20102"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13679\u2010015\u20100166\u20107"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11695\u2010018\u20103301\u20101"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.91a.24068"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2022\u2010060641"}],"container-title":["Pediatric Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ped4.70040","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ped4.70040","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ped4.70040","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T11:52:08Z","timestamp":1787917928000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ped4.70040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":82,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/ped4.70040"],"URL":"https:\/\/doi.org\/10.1002\/ped4.70040","archive":["Portico"],"relation":{},"ISSN":["2096-3726","2574-2272"],"issn-type":[{"value":"2096-3726","type":"print"},{"value":"2574-2272","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]},"assertion":[{"value":"2025-09-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}