2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Diagnostic Yield of Genetic Testing for Non-Syndromic Early-Onset Obesity in a Multidisciplinary Pediatric Obesity Clinic

Diagnostic Yield of Genetic Testing for Non-Syndromic Early-Onset Obesity in a Multidisciplinary Pediatric Obesity Clinic

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Pdf Summary

This study aimed to determine the utility and diagnostic yield of clinical genetic testing for non-syndromic early-onset obesity (NSO) in a pediatric obesity clinic. The clinic evaluated patients with a BMI > 99% before the age of 5, using a multidisciplinary approach involving an endocrinologist, medical geneticist, and genetic counselor.<br /><br />A total of 84 patients with NSO were included in the study. The genetic cause of obesity was suspected if patients had hyperphagia or discordant weight gain with lifestyle interventions. Genetic testing recommendations included an obesity gene panel, chromosomal microarray analysis (CMA), and whole exome sequencing (WES).<br /><br />Among the patients, 5 had positive genetic testing results. The most common gene implicated was MC4R, with pathogenic variants identified in 4 patients. One patient had a pathogenic variant in the KSR2 gene. All patients with positive genetic testing results had features of hyperphagia and had an affected parent with autosomal dominant inheritance.<br /><br />The diagnostic rate of genetic testing through the obesity gene panel was 10.6% in this cohort. The authors concluded that diagnostic genetic testing for early-onset NSO can yield positive results in at least 10% of cases, and confirmation of a molecular diagnosis can impact medical management and have implications for family members.<br /><br />However, the study acknowledged limitations, including the selective population of children with early-onset obesity and barriers to completing recommended genetic testing due to insurance pre-authorization.<br /><br />Further studies are needed to determine additional factors that can help identify cases of NSO that are more likely due to an underlying genetic etiology.

Asset Subtitle

Co-Author - Farah A. Ladha, MS, CGC; Co-Author - Stephanie Sisley, MD; Presenting Author - Claudia R. Soler-Alfonso, MD, FACMG;

Meta Tag

Etiology

Genetic Testing

Phenotype

Co-Author Farah A. Ladha, MS, CGC

Co-Author Stephanie Sisley, MD

Presenting Author Claudia R. Soler-Alfonso, MD, FACMG

Keywords

clinical genetic testing

non-syndromic early-onset obesity

pediatric obesity clinic

multidisciplinary approach

obesity gene panel

chromosomal microarray analysis

whole exome sequencing

hyperphagia

diagnostic rate

genetic etiology