Genetic Obesity Disorders: Body Mass Index Trajectories and Age of Onset of Obesity Compared with Children with Obesity from the General Population

Abstract

We sought to assess body mass index trajectories of children with genetic obesity to identify optimal early age of onset of obesity (AoO) cut-offs for genetic screening. This longitudinal, observational study included growth measurements from birth onward of children with nonsyndromic and syndromic genetic obesity and control children with obesity from a population-based cohort. Diagnostic performance of AoO was evaluated. We describe the body mass index trajectories of 62 children with genetic obesity (29 nonsyndromic, 33 syndromic) and 298 controls. Median AoO was 1.2years in nonsyndromic genetic obesity (0.4 and 0.6years in biallelic LEPR and MC4R; 1.7 in heterozygous MC4R); 2.0years in syndromic genetic obesity (0.9, 2.3, 4.3, and 6.8years in pseudohypoparathyroidism, Bardet-Biedl syndrome, 16p11.2del syndrome, and Temple syndrome, respectively); and 3.8years in controls. The optimal AoO cut-off was ≤3.9years (sensitivity, 0.83; specificity, 0.49; area under the curve, 0.79; P<.001) for nonsyndromic and ≤4.7years (sensitivity, 0.82; specificity, 0.37; area under the curve, 0.68; P=.001) for syndromic genetic obesity. Optimal AoO cut-off as single parameter to determine which children should undergo genetic testing was ≤3.9years. In case of older AoO, additional features indicative of genetic obesity should be presentto warrant genetic testing. Optimal cut-offs might differ across different races and ethnicities.