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MC4R Deficiency — Adult Monogenic Obesity
A 34-year-old man with lifelong hyperphagia and early-onset obesity (BMI 44 kg/m²) reports strong family history of severe obesity across generations. Height is tall for family, lean mass preserved; no syndromic features. Outline evaluation and management.
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Lifestyle + anti-obesity meds; consider clinical trial access; setmelanotide generally not indicated for isolated MC4R variants (unless specific upstream defects)
Order targeted genetic panel/exome including MC4R and leptin–melanocortin pathway genes
Exclude secondary endocrine causes (TSH, cortisol if indicated) and medication-induced weight gain
Suspect MC4R pathway defect with childhood-onset hyperphagia, severe obesity, autosomal dominant pattern
Longitudinal cardiometabolic surveillance (BP, lipids, A1c), sleep apnea screening; family counseling
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