Development of Dysplastic Nevi in a Child with LEPR Deficiency Treated with Setmelanotide

Area of Science:

• Endocrinology
• Genetics
• Dermatology

Background:

• Setmelanotide is approved for rare monogenic obesity linked to POMC, LEPR, PCSK1 mutations, or Bardet-Biedl syndrome.
• It targets melanocortin-4 receptors (MC4R) but also weakly stimulates melanocortin-1 receptors (MC1R), potentially affecting pigmentation.

Purpose of the Study:

• To report the first pediatric case of dysplastic nevi development during setmelanotide treatment in a patient with LEPR-related monogenic obesity.

Main Methods:

• Case report of a 12-year-old boy with homozygous LEPR mutation treated with setmelanotide.
• Monitoring of skin pigmentation changes, including nevi.
• Excision and histopathological examination of two nevi with observed pigmentation changes.

Main Results:

• The patient developed skin hyperpigmentation and darkening of nevi after initiating setmelanotide.
• Histopathology of excised nevi revealed dysplastic features.
• This suggests potential MC1R-mediated melanocytic activity.

Conclusions:

• Setmelanotide treatment may be associated with the development of dysplastic nevi in pediatric patients with LEPR mutations.
• Further investigation into MC1R-mediated side effects is warranted.
• Temporary discontinuation of therapy was implemented due to these findings.