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Science-based information about the melanocortin-4 receptor pathway


Melanocortin-4 receptor pathway information

Scientific information

Find out more about the latest of our cutting-edge research available to the community


Congresses and meetings relevant to rare melanocortin-4 receptor pathway diseases throughout 2024


Access learning tools, educational resources and additional information about rare melanocortin-4 receptor pathway diseases

Stockholm: 11-14 May

European Congress of Endocrinology 2024

Rhythm-sponsored Hub session

Rhythm Pharmaceuticals

Don't miss the ECE 2024 Hub session of Dr. Fintini (Bambino Gesù Children's Hospital, Rome): Rare hypothalamic melanocortin-4 receptor pathway diseases: hyperphagia and early-onset, severe obesity

Recording available now! Click here.

© 2024. Rhythm Pharmaceuticals, Inc. All rights reserved. Rhythm and its logo are trademarks of Rhythm Pharmaceuticals, Inc. INT-DSE-2400059 - 05/2024

Welcome to path4HCPs

Here you can learn more about rare melanocortin-4 receptor (MC4R) pathway diseases, their diagnosis and management.

Rare MC4R pathway diseases can be caused by genetic variants within the pathway (part of the central melanocortin pathway). These changes can impair signalling in the pathway that controls hunger and can be a root cause of increased appetite and body weight.1

To accurately diagnose and care for those possibly living with a rare MC4R pathway disease, it is crucial to undertake a detailed observation of the patient and gain confirmation of any underlying genetic cause.

A proper understanding of a root cause of the disease allows for appropriate management and care of patients.1

Here you can find information about rare MC4R pathway diseases, including:

Bardet-Biedl syndrome

Bardet-Biedl syndrome (BBS) is a rare ciliopathy, resulting from genetic variants within the BBS family of genes. This heterogeneous genetic disease presents with a variety of symptoms that can evolve over time, including:2,3

  • Cognitive impairment
  • Early-onset, severe obesity
  • Genital anomalies
  • Hyperphagia
  • Polydactyly
  • Renal disease
  • Visual impairments

Diagnosis of BBS is based on clinical findings; diagnosis confirmed by genetic testing.3

Pro-opiomelanocortin deficiency and leptin receptor deficiency

Pro-opiomelanocortin (POMC) and leptin receptor (LEPR) deficiencies are genetically identifiable rare MC4R pathway diseases (known as monogenic obesity). They are autosomal recessive inherited diseases caused by variants in the POMC or LEPR gene. Diagnosis of POMC and LEPR deficiency may be suspected based on clinical manifestations, such as hyperphagia and early-onset obesity, and is confirmed by genetic testing.2

Learn more about the cardinal symptoms of rare melanocortin-4 receptor pathway diseases

Dr Ashley Shoemaker, Vanderbilt University Medical Center and Dr Ilene Fennoy, New York-Presbyterian Hospital/Columbia University Medical Center explain more about the clinical presentation of the cardinal symptoms of rare MC4R pathway diseases, hyperphagia and early-onset severe obesity. Including key signs, symptoms and cues to look for during a consultation.

Latest videos

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How to identify genetic causes of obesity and...
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Hyperphagia and early-onset, severe obesity:...


  1. 1. Yazdi F et al, Peerj, 2015;3;e856.
  2. 2. Huvenne H, et al. Obes Facts. 2016;9:158-73.
  3. 3. Forsythe et al., Orphanet Journal. 2023;18(12).