ESPE Abstracts

Introduction: Early onset of obesity has very severe consequences for the rest of the life which leads to morbid obesity as adults, dyslipidemia, hypertension, diabetes mellitus, sleep apnea and fatty liver disease. Recently, various genetic panels have been available and are quickly becoming a standard of care to screen children with genetic panel for obesity. However, most of these variations in ethnically diverse populations have not been extensively studied.

Methods: We collected buccal swab specimens from children with excessive weight gain in the first two years of life without history of hypotonia. The subjects were enrolled from the Endocrine clinics of Children’s Hospital of Orange County. Genetic panel of obesity was performed as a part of Uncovering Rare Obesity® Program by Prevention Genetics labs. The ethnic background of the subject for predominantly Hispanic with the BMI percentile of a greater than 99% or more than two standard deviations above the mean.

Results: 18 different children were found to have at least one variation in the genes linked to early onset obesity. Out of the 18 majority of these variation were classified under interpretation as "uncertain". Only one variation of PCSK1 gene was classified as "risk" and this subject was heterogenous (het) for c.661A>G, p.Asn221Asp change. The gene variation, which was likely pathogenic was het for c.3082+1G>T change leading to a GT donor in the VPS13B gene. 10 out of 18 subjects had mono-allelic variation in these gene. 2 subjects had biallelic variations, 4 subjects had variations in 3 different genes. 1 subject had variations in 4 genes and 1 in 5 genes. Some of the commonly seen gene variation in our cohort was as follows:- 2 subjects were het for the c.1996G>A, p.Val666Met in the PLXNA4 gene; 2 subjects were het for c.2050C>T, p.Pro684Ser in the RAI1 gene; 2 subjects were het for c.2105T in the PCNT gene, 2 subjects were also het for c.806T>A, p.Ile269Asn in the MC4R gene. Bardet-Biedl syndrome (BBS) or Alström syndrome related genes were found in 7 out of 18 subjects.

Conclusion: Majority of gene variations in these children with early onset severe obesity are reported as "uncertain". As more children will be identified with various gene mutations the phenotype-genotype link might be established. Another important thing to note is that in most children had single allelic variations. However 8/18 had polygenic variations. In ~ 40% had gene variations in the BBS or Alström syndrome related genes pathway.