​​​Keeping Genetic Obesity in Your Differential

Genetic obesity syndromes are rare — less than 10% of children diagnosed with severe obesity will have a genetic cause — but making the distinction between genetic and acquired obesity may impact treatment options. Diagnosis can be difficult, however, because many syndromes are related to genetic obesity. Symptoms such as early-onset obesity, hyperphagia from a very early age or weight gain exceeding what is expected for a child’s diet and exercise profile can be helpful clues that lead to genetic testing.  

Stephanie Sisley, MD, medical director of the Genetic Disorders of Obesity Program and associate research director of the pediatric endocrine division at Texas Children’s Hospital, is part of a small but dedicated community of physicians who are helping bring genetic causes of obesity to light. 

“Our clinic is designed to be a diagnostic clinic. Because genetic forms of obesity are so varied, you would not typically expect a general pediatrician to know all the different syndromes that can cause obesity. Additionally, performing genetic testing and knowing what to do with the results are specialized skills,” said Dr. Sisley.  

Diagnosing a genetic cause for obesity 

Children who have had severe obesity starting before age 5 are eligible for genetic testing in the clinic. At the initial visit, Dr. Sisley is primarily interested in diet and lifestyle at home, but also screens for hyperphagia and familial obesity. Patients and their families also see a genetics counselor and pediatric geneticist who focus on developmental milestones, exam findings and a more thorough family history in addition to providing guidance about the genetic testing process.  

“We can’t officially diagnose genetic obesity without either a positive genetic test or meeting clinical criteria for some syndromes like Bardet-Biedl syndrome,” said Dr. Sisley.  

Of the very rare syndromes that Dr. Sisley sees in her clinic, Bardet-Biedl syndrome, characterized by abdominal obesity and intellectual impairment as well as other symptoms, is a common finding. Some patients, however, will have the signs of hyperphagia and early-onset obesity but negative results through genetic testing.  

“We refer patients to dietitians who can spend time discussing specific diet changes for each patient. I try to focus on supporting the parent,” said Dr. Sisley. “They are the ones who have to tell the child ‘no’ and enforce a healthy lifestyle. It’s really easy for me to tell patients ‘please eat healthy’ but it can be especially difficult for parents to enforce it.” 

Medical management of obesity in children 

Liraglutide and semaglutide, both GLP-1 inhibitors used in adult diabetes management, are approved for use in treating obesity in children over age 12. Setmelanotide, a different appetite-suppressing medication, can be prescribed for children as young as six years old who are diagnosed with certain obesity-related syndromes. Another approved appetite-suppressing medication for children is a phentermine/topiramate combination, which was approved in 2022 for children age 12 and older.  

For children younger than 12, treatment focuses on lifestyle modification and off label use of medications approved for young children that have a side effect of appetite suppression, such as stimulants used for attention deficit/hyperactivity disorder.  

“If someone has genetic obesity that’s impacting their ability to feel full and their ability to burn energy, it can be difficult for them to lose weight without medications or a very restrictive environment,” said Dr. Sisley. “When I prescribe medications to treat hyperphagia, this is to give patients a fighting chance. I don’t think that patients will be able to implement a healthy diet without some appetite suppression.” 

Medications are not, of course, a magic bullet, and only work to assist with diet modifications.  

“All of the medications have guidelines. If you don’t meet certain criteria, you shouldn’t continue it after 3 or 4 months,” said Dr. Sisley. Most of her patients who are unable to maintain a healthy diet and exercise habits are also unable to meet the necessary criteria to continue the medication.  

Many providers are watching the weight of their patients due to societal and medical concerns about rising rates of obesity in children. Dr. Sisley encourages primary care providers to refer children who have shown signs of weight gain and hyperphagia from a young age for genetic testing. She also recommends considering the use of weight management medications even for children who do not have a genetic cause for their obesity.  

Refer a patient to the Genetic Disorders of Obesity Clinic through the online portal.