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Pediatric Obesity: Endocrinologic and Genetic Etiologies and Management

  • Obesity and Diet (G. Rao, Section Editor)
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Abstract

Purpose of Review

The prevalence of pediatric obesity has increased significantly over the past couple of generations. While monogenic obesity, syndromic obesity, and endocrinopathies associated with obesity have been increasingly recognized, they do not account for the increase in prevalence. We describe these rare conditions and the dysregulation of neuropathways in obesity and review successes and failures in treatments in both syndromic and nonsyndromic obesity.

Recent Findings

The best-described form of syndromic obesity is Prader–Willi Syndrome (PWS). While recent pharmacotherapies (specifically beloranib) demonstrated improvements in weight in PWS, the unfortunate adverse effect of deep vein thrombosis and pulmonary embolism necessitated the halting of its further development. Additional treatments are in development which target the signaling of ghrelin and other hypothalamic targets known to be dysregulated in PWS. For nonsyndromic obesity, lifestyle modifications remain the mainstay of treatment. However, recent large-scale interventions have had disappointing results. Bariatric surgery in children holds some promise, though complications and reoperations are common. Pharmacotherapies have been developed that treat rare monogenic forms of obesity, including MC4R agonists, which hold promise for these uncommon explanations for early childhood weight gain. There is evidence that methylation patterns in key genes in the neuroregulation of appetite are altered in individuals with obesity. Interestingly, this altered methylation is evident in sperm, which may have an impact on the heritability of gene expression across generations.

Summary

Pediatric obesity is complex and multifactorial. Efforts in rare monogenic and syndromic obesity may give rise to potential treatment opportunities in circumstances where lifestyle interventions are unsuccessful.

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Authors and Affiliations

  1. Division of Pediatric Endocrinology, Rainbow Babies and Children’s Hospital, University Hospitals Cleveland Medical Center, Cleveland, OH, USA

    Shashikala Gowda, Tasa Seibert, Naveen Uli & Ryan Farrell

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  1. Shashikala Gowda
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Correspondence to Ryan Farrell.

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Conflict of Interest

Shashikala Gowda and Tasa Seibert declare that they have no conflict of interest.

Ryan Farrell has been principal investigator and/or coinvestigator for three different industry-sponsored pharmaceutical trials for Prader–Willi Syndrome (GLWL, Soleno, and Levo Therapeutics).

Naveen Uli has been principal investigator and/or coinvestigator for three different industry-sponsored pharmaceutical trials for Prader–Willi Syndrome (GLWL, Soleno, and Levo Therapeutics). He also was a coinvestigator for the Childhood Obesity Prevention and Treatment Research Consortium (COPTR).

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Gowda, S., Seibert, T., Uli, N. et al. Pediatric Obesity: Endocrinologic and Genetic Etiologies and Management. Curr Cardiovasc Risk Rep 13, 39 (2019). https://doi.org/10.1007/s12170-019-0632-y

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