387 - Advantages of genetic testing in the evaluation of pediatric obesity

Child obesity rates continue to rise, with 19.3% of children ages 2 to 19 affected by obesity.  Genetics contribute to 40 to 70% of obesity, yet treatment is often limited to lifestyle modification and rarely involves genetic testing.

Objective: The following cases demonstrate advantages to genetic testing for obesity.

Design/Methods:

Retrospective chart review

Results:

A: 9 yo F with obesity, hypothyroidism and increasing BMI despite lifestyle modification.  Genetic testing revealed heterozygosity for two MC4R gene variants.  The hypothalamic melanocortin 4 receptor (MC4R) pathway regulates weight by influencing hunger, satiety, metabolic rate and energy balance.  This result provided validation for the parents and eligibility for a new medication, an MC4R agonist, setmelanotide, approved to treat patients with gene variants affecting this pathway.

B: 2 yo M with developmental delay and obesity.  Genetic testing revealed homozygosity for a pathogenic variant in BBS12, associated with Bardet-Biedl syndrome (BBS).  BBS is a non-motile ciliopathy with visual impairment, obesity, postaxial polydactyly, cognitive impairment, hypogonadotropic hypogonadism, and renal disease.  Early identification of BBS facilitated prompt interventions with ophthalmology and nephrology.  Additionally, addressing developmental delay is imperative as many patients with BBS develop visual impairment or blindness by adolescence.  Patients with BBS are also eligible for setmelanotide.

C: 2 yo M with epilepsy and obesity.  His BMI increased significantly after developing seizures.  Genetic testing revealed heterozygous variants in genes LZTFL1 and MKKS of unknown significance.  Essentially negative genetic testing redirected treatment efforts to identifying other potential contributors like medications (Trileptal) or excess calories (large portions, grazing, calorie dense foods, sugary drinks).  His neurologist discussed alternate options, like topiramate, if BMI increases despite lifestyle modification.

Conclusion(s):

Rising rates of childhood obesity and comorbidities like type 2 diabetes, hypertension, and depression highlight the need to expand obesity treatment options.  There are many contributors to obesity like social determinants of health, adverse childhood events, toxic stress, and genetics.  Genetic testing can validate efforts of patients who are unable to reduce their BMI; identify genetic etiologies for obesity; identify genetic syndromes that require multidisciplinary teams and interventions; and connect patients with existing and future medications to treat obesity.  Even negative tests narrow the differential of obesity etiologies.