TY - JOUR
T1 - Genetic Obesity Disorders
T2 - Body Mass Index Trajectories and Age of Onset of Obesity Compared with Children with Obesity from the General Population
AU - Abawi, Ozair
AU - Wahab, Rama J.
AU - Kleinendorst, Lotte
AU - Blankers, Lizette A.
AU - Brandsma, Ammelies E.
AU - van Rossum, Elisabeth F. C.
AU - van der Voorn, Bibian
AU - van Haelst, Mieke M.
AU - Gaillard, Romy
AU - van den Akker, Erica L. T.
N1 - Funding Information: Supported by the Elisabeth Foundation (project name ObesEcare), a nonprofit foundation supporting academic research. Publisher Copyright: © 2023 The Author(s)
PY - 2023/11/1
Y1 - 2023/11/1
N2 - Objective: 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. Study design: 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. Results: We describe the body mass index trajectories of 62 children with genetic obesity (29 nonsyndromic, 33 syndromic) and 298 controls. Median AoO was 1.2 years in nonsyndromic genetic obesity (0.4 and 0.6 years in biallelic LEPR and MC4R; 1.7 in heterozygous MC4R); 2.0 years in syndromic genetic obesity (0.9, 2.3, 4.3, and 6.8 years in pseudohypoparathyroidism, Bardet-Biedl syndrome, 16p11.2del syndrome, and Temple syndrome, respectively); and 3.8 years in controls. The optimal AoO cut-off was ≤3.9 years (sensitivity, 0.83; specificity, 0.49; area under the curve, 0.79; P < .001) for nonsyndromic and ≤4.7 years (sensitivity, 0.82; specificity, 0.37; area under the curve, 0.68; P = .001) for syndromic genetic obesity. Conclusions: Optimal AoO cut-off as single parameter to determine which children should undergo genetic testing was ≤3.9 years. In case of older AoO, additional features indicative of genetic obesity should be present to warrant genetic testing. Optimal cut-offs might differ across different races and ethnicities.
AB - Objective: 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. Study design: 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. Results: We describe the body mass index trajectories of 62 children with genetic obesity (29 nonsyndromic, 33 syndromic) and 298 controls. Median AoO was 1.2 years in nonsyndromic genetic obesity (0.4 and 0.6 years in biallelic LEPR and MC4R; 1.7 in heterozygous MC4R); 2.0 years in syndromic genetic obesity (0.9, 2.3, 4.3, and 6.8 years in pseudohypoparathyroidism, Bardet-Biedl syndrome, 16p11.2del syndrome, and Temple syndrome, respectively); and 3.8 years in controls. The optimal AoO cut-off was ≤3.9 years (sensitivity, 0.83; specificity, 0.49; area under the curve, 0.79; P < .001) for nonsyndromic and ≤4.7 years (sensitivity, 0.82; specificity, 0.37; area under the curve, 0.68; P = .001) for syndromic genetic obesity. Conclusions: Optimal AoO cut-off as single parameter to determine which children should undergo genetic testing was ≤3.9 years. In case of older AoO, additional features indicative of genetic obesity should be present to warrant genetic testing. Optimal cut-offs might differ across different races and ethnicities.
KW - MC4R
KW - adiposity
KW - genetic test
KW - leptin-melanocortin pathway
KW - monogenic obesity
KW - syndromic obesity
UR - http://www.scopus.com/inward/record.url?scp=85168372684&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jpeds.2023.113619
DO - https://doi.org/10.1016/j.jpeds.2023.113619
M3 - Article
C2 - 37473986
SN - 0022-3476
VL - 262
JO - Journal of pediatrics
JF - Journal of pediatrics
M1 - 113619
ER -