Monogenic Obesity

MC4R Monogenic Obesity Genetic Test

Monogenic obesity is a group of rare genetic disorders characterized by severe, early-onset obesity as a primary feature. Pathogenic variants in the MC4R gene are among the most common causes of non-syndromic monogenic obesity, affecting appetite regulation and metabolism through hypothalamic pathways.

Detection of MC4R variants can be done individually or as part of the GENOSOPHY® Monogenic Obesity Panel, which also includes genes such as LEP, LEPR, POMC, and PCSK1 involved in energy balance and appetite regulation.

Conditions Covered by the GENOSOPHY® Genetic Test

The test detects pathogenic variants in the MC4R gene, associated with:

• Severe early-onset obesity (BMI > 3 SD in children, BMI > 40 in adults)
• Hyperphagia and impaired satiety
• Accelerated growth and increased lean body mass
• Higher risk of metabolic complications (e.g., type 2 diabetes, hypertension)

Who Should Consider This Test?

• Individuals with severe early-onset obesity
• Children with rapid weight gain and overeating
• Patients with a family history of early-onset obesity, especially with autosomal dominant inheritance patterns
• Individuals with low energy expenditure or resistance to weight loss
• People with impaired satiety or comorbid conditions like type 2 diabetes, hypertension, or dyslipidemia

Clinical Benefits

Diagnosis

• Confirmation of a genetic cause of severe obesity
• Differential diagnosis between monogenic and polygenic forms of obesity

Prognosis

• Assessment of future risk for metabolic complications
• Guidance for personalized prevention strategies

Management

• Targeted pharmacological interventions (e.g., GLP-1 receptor agonists)
• Precision nutritional interventions – see GENOSOPHY®’s personalized nutrition support services
• Family genetic counseling

Test Procedure

1. Saliva or blood sample collection
2. Analysis of the MC4R gene using Next-Generation Sequencing (NGS)
3. Results delivered within approximately 5 weeks

Optional: Expert genetic counseling and result interpretation by Professors of the National and Kapodistrian University of Athens (EKPA), available as a separate service.