Endocrine Abstracts

Background: Obtaining a genetic diagnosis for obesity offers various benefits; it enables screening of associated pathology, reduces stigma by demonstrating an organic cause, and guides potential access to emerging novel medications. The number of genes recognised as causative of severe obesity has significantly increased in recent years. With obesity prevalence rising, stratifying patients for genetic testing becomes challenging. Our obesity service genetic testing pathway comprises offering the R149 NHS genomic panel (or pre-2020 the Cambridge Genetics of Obesity Study (GOOS) from which the R149 panel evolved) for children presenting with severe obesity <5 years old and/or hyperphagia, and additional array CGH for those with co-existing autism spectrum disorder (ASD), learning difficulties (LD) or developmental delay (DD).

Aims/Methods: Through electronic case-note review, we assessed the diagnostic yield of this testing pathway and patient characteristics for the first 80 patients in our service with known obesity genetic results from 2014-2023.

Results: 80 patients underwent GOOS/R149 testing. 24/80 also had array CGH. 64/80 had documented obesity onset <5 years and 58/80 had hyperphagia. 21/80 had congenital abnormalities/syndromic features. 38/80 had ASD. 43/80 had LD/DD. 10/80 patients had a positive R149 result (9 MC4R mutation, 1 leptin receptor deficiency). All (10/10) had obesity onset <5 years and hyperphagia. 9/10 had family history (FH) of obesity. 4/10 had ASD and a further 3/10 had mild LD/DD. Of the 24/80 patients who had array CGH, 21/24 had documented obesity onset <5 years. 19/24 had hyperphagia. 4/24 had congenital abnormalities/syndromic features. 16/24 had FH of obesity. 15/24 had ASD. 15/24 had LD/DD. 5/24 patients had a positive array CGH result, of whom 3 had incidental findings of no/unknown/unrelated significance to obesity, while 2 had an abnormality associated with severe early-onset obesity (19p13.3 duplication, 1q21.1-21.2 duplication). Both had obesity onset <5 years and hyperphagia. Neither had congenital abnormalities/syndromic features. One had FH of obesity. Both had ASD with LD/DD.

Conclusions: Genetic testing for children with severe obesity with onset <5 years old and/or hyperphagia appears to have high diagnostic yield. Additional array CGH for those with co-existing ASD or LD/DD may yield obesity-associated genetic diagnoses.