Description

Seattle Children’s Hospital is retiring clinical ordering of the Uncovering Rare Obesity Gene Panel. Our Laboratory Stewardship Committee determined that the panel is of low clinical utility and patients should be referred to Clinical Genetics for genetic test coordination (see details below).  

Historically, patients that were ≤18 years of age (BMI ≥97th percentile) or ≥19 years of age (BMI ≥40) with a history of childhood obesity were eligible to receive PreventionGenetics’ Uncovering Rare Obesity Gene Panel. 

In 2024, representatives from Endocrinology, Nutrition, Clinical Genetics, and the Laboratory Stewardship Committee collaborated to review the clinical utility of the sponsored genetic panel and current clinical practice guidelines.  According to the 2023 American Academy of Pediatrics clinical practice guidelines, patients with severe obesity (defined as a BMI ≥ 120% of the 95th percentile) with onset before age 5 and/or hyperphagia may be evaluated for a genetic cause. For patients with intellectual disability, developmental delay, and/or congenital anomalies, the 2021 American College of Medical Genetics and Genomics clinical practice guidelines strongly recommend exome or genome sequencing.  

To align with current clinical practice guidelines, the improved genetic testing algorithm for pediatric obesity is as follows:  

1. Patient is evaluated in Endocrinology/Nutrition/Another clinic. Genetic testing is recommended.  
2. Patient is referred to Clinical Genetics. 
   • Patients with severe obesity with onset before age 5 and/or hyperphagia will be evaluated for a targeted panel* to inform pharmacotherapy.
   • Patients with concerns beyond obesity (such as intellectual disability, developmental delay, congenital anomalies, etc.) will be evaluated for broader testing such as exome or genome sequencing.  

*The targeted panel will consist of MC4R, POMC, PCSK1, LEPR, and BBS genes to inform eligibility for setmelanotide. In December 2024, the FDA approved setmelanotide use in patients as young as 2 years old with melanocortin-4 receptor (MC4R) pathway deficiencies caused by variants in MC4R, POMC, PCSK1, LEPR, and BBS genes.  

If a provider wishes to discuss Uncovering Rare Obesity Gene Panel ordering further, a Laboratory Genetic Counselor may be reached at LabGC@seattlechildrens.org. 

References 

1. Rhythm Pharmaceuticals, Inc. “Rhythm Pharmaceuticals announces FDA approval of IMCIVREE® (setmelanotide) for patients as young as 2 years old.” GlobeNewswire News Room (2024). https://www.globenewswire.com/news-release/2024/12/20/3000811/0/en/Rhythm-Pharmaceuticals-Announces-FDA-Approval-of-IMCIVREE-setmelanotide-for-Patients-as-Young-as-2-Years-Old.html. (Accessed: 15th May 2025) 
2. Hampl, Sarah E et al. “Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity.” Pediatrics vol. 151,2 (2023): e2022060640. doi:10.1542/peds.2022-060640 
3. Manickam, Kandamurugu et al. “Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG).” Genetics in medicine : official journal of the American College of Medical Genetics vol. 23,11 (2021): 2029-2037. doi:10.1038/s41436-021-01242-6