Rare Genetic Diseases of Obesity

The symptoms are there. Can you recognize them? Learn about the underlying pathophysiology, key clinical characteristics, and the importance of diagnosis below.

What are rare genetic diseases of obesity?

General obesity is a subset of obesity that arises from the interactions between an at-risk genetic profile and environmental risk factors, such as physical inactivity, excessive caloric intake, the intrauterine environment, medications, and socioeconomic status.1

Rare genetic diseases of obesity represent a subset of obesity that arises predominantly from impactful variants in a gene, resulting in the loss of function of key systems that regulate energy balance.2 The melanocortin-4 receptor (MC4R) pathway is one such key system.2,3

The MC4R Pathway

The MC4R pathway in the hypothalamus is a key signaling pathway responsible for regulating hunger, food intake, and energy expenditure, which consequently affects body weight.2,5 Learn more about this pathway in the Rare MC4R Pathway Diseases - Mechanism of Disease Video.

The importance of the MC4R pathway's control of energy balance has made it a compelling target for potential weight-regulating treatments.

Disease Spotlight

Learn more about Bardet-Biedl syndrome (BBS).

Key Clinical Characteristics

Rare genetic diseases of obesity can present with a variety of clinical characteristics, but hyperphagia and early-onset, severe obesity are common features that separate them from other forms of obesity.2,5,6 Hyperphagia is an insatiable pathological hunger and preoccupation with food that has broad impacts on patients and their families.5,7,8

Importance of Diagnosis

A correct diagnosis may help patients, caregivers, and treaters overcome challenges surrounding the management of rare genetic diseases of obesity.

Genetic Testing

Genetic testing can aid in the diagnosis of rare genetic diseases of obesity. Guidelines and experts recommend genetic testing for patients with clinical features of rare genetic diseases of obesity, including hyperphagia and early-onset, severe obesity.2,9,12 Early diagnosis of rare genetic diseases of obesity may help inform treatment, including early obesity management.

aBefore 5 years of age.

Rhythm has developed several initiatives to identify patient populations who may have rare genetic diseases of obesity. Uncovering Rare Obesity® is a no-charge, US-based, comprehensive genetic testing program for rare genetic diseases of obesity. The program includes a gene panel of nearly 80 genes and offers online test ordering, digital report access, and support for results interpretation.

If you think your patient may have a rare genetic disease of obesity and would like more information on genetic testing, please visit


Genetic Obesity Learning Development (GOLD) Academy

Rhythm's GOLD Academy brings together health care providers to learn about rare genetic causes of obesity and the role of the MC4R pathway in regulating hunger, food intake, energy expenditure, and consequently body weight.

GOLD Academy programs, which are US-based non-CME programs sponsored by Rhythm Pharmaceuticals, are physician-led, interactive presentations.

Learn More


  1. Goodarzi MO. Lancet Diabetes Endocrinol. 2018;6(3):223-236.
  2. Huvenne H, et al. Obes Facts. 2016;9(3):158-173.
  3. da Fonseca ACP, et al. J Diabetes Complications. 2017;31(10):1549-1561.
  4. Lu Q, et al. J Mol Endocrinol. 2019;62(1):37-46.
  5. Heymsfield SB, et al. Obesity (Silver Spring). 2014;22(suppl 1):S1-S17.
  6. Kohlsdorf K, et al. Int J Obes (Lond). 2018;42(9):1602-1609.
  7. Phillips GA, et al. Poster presented at: 27th Annual Conference of the International Society for Quality of Life Research; October 21-24, 2020; Virtual.
  8. Hamlington B, et al. PLoS One. 2015;10(10):e0140705.
  9. Styne DM, et al. J Clin Endocrinol Metab. 2017;102(3):709-757.
  10. Pomeroy J, et al. Pediatr Obes. 2021;16(2):e12703.
  11. Sawyer SL, et al. Clin Genet. 2016;89(3):275-284.
  12. van der Valk ES, et al. Obes Rev. 2019;20(6):795-804.

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