Obesity is a multifactorial and complex disease that often manifests in early childhood with a lifelong burden. Polygenic and monogenic obesity are driven by the interaction between genetic predisposition and environmental factors. Polygenic variants are frequent and confer small effect sizes. Rare monogenic obesity syndromes are caused by defined pathogenic variants in single genes with large effect sizes. Most of these genes are involved in the central nervous regulation of body weight; for example, genes of the leptin–melanocortin pathway. Clinically, patients with monogenic obesity present with impaired satiety, hyperphagia and pronounced food-seeking behaviour in early childhood, which leads to severe early-onset obesity. With the advent of novel pharmacological treatment options emerging for monogenic obesity syndromes that target the central melanocortin pathway, genetic testing is recommended for patients with rapid weight gain in infancy and additional clinical suggestive features. Likewise, patients with obesity associated with hypothalamic damage or other forms of syndromic obesity involving energy regulatory circuits could benefit from these novel pharmacological treatment options. Early identification of patients affected by syndromic obesity will lead to appropriate treatment, thereby preventing the development of obesity sequelae, avoiding failure of conservative treatment approaches and alleviating stigmatization of patients and their families.

肥胖是一种多因素和复杂的疾病，通常在儿童早期表现出来，并带来终生负担。多基因和单基因肥胖是由遗传易感性和环境因素之间的相互作用驱动的。多基因变体很常见并且具有较小的效应量。罕见的单基因肥胖综合征是由具有大效应量的单个基因中明确的致病变异引起的。这些基因中的大多数都参与了体重的中枢神经调节。例如，瘦素-黑皮质素通路的基因。临床上，单基因肥胖患者在儿童早期表现为饱腹感受损、食欲过盛和明显的寻食行为，导致严重的早发性肥胖。随着针对中枢黑皮质素途径的单基因肥胖综合征出现新的药物治疗选择，建议对婴儿期体重快速增加和其他临床提示特征的患者进行基因检测。同样，与下丘脑损伤或其他形式的涉及能量调节回路的综合性肥胖相关的肥胖患者可以从这些新的药物治疗选择中受益。早期识别受综合征性肥胖影响的患者将导致适当的治疗，从而防止肥胖后遗症的发展，避免保守治疗方法的失败并减轻患者及其家属的污名化。建议对婴儿期体重快速增加和其他临床提示特征的患者进行基因检测。同样，与下丘脑损伤或其他形式的涉及能量调节回路的综合性肥胖相关的肥胖患者可以从这些新的药物治疗选择中受益。早期识别受综合征性肥胖影响的患者将导致适当的治疗，从而防止肥胖后遗症的发展，避免保守治疗方法的失败并减轻患者及其家属的污名化。建议对婴儿期体重快速增加和其他临床提示特征的患者进行基因检测。同样，与下丘脑损伤或其他形式的涉及能量调节回路的综合性肥胖相关的肥胖患者可以从这些新的药物治疗选择中受益。早期识别受综合征性肥胖影响的患者将导致适当的治疗，从而防止肥胖后遗症的发展，避免保守治疗方法的失败并减轻患者及其家属的污名化。