A systematic review of genetic syndromes with obesity

Abstract

Syndromic monogenic obesity typically follows Mendelian patterns of inheritance and involves the co-presentation of other characteristics, such as mental retardation, dysmorphic features and organ-specific abnormalities. Previous reviews on obesity have reported 20 to 30 syndromes but no systematic review has yet been conducted on syndromic obesity. We searched seven databases using terms such as 'obesity', 'syndrome' and 'gene' to conduct a systematic review of literature on syndromic obesity. Our literature search identified 13,719 references. After abstract and full-text review, 119 relevant papers were eligible, and 42 papers were identified through additional searches. Our analysis of these 161 papers found that 79 obesity syndromes have been reported in literature. Of the 79 syndromes, 19 have been fully genetically elucidated, 11 have been partially elucidated, 27 have been mapped to a chromosomal region and for the remaining 22, neither the gene(s) nor the chromosomal location(s) have yet been identified. Interestingly, 54.4% of the syndromes have not been assigned a name, whereas 13.9% have more than one name. We report on organizational inconsistencies (e.g. naming discrepancies and syndrome classification) and provide suggestions for improvements. Overall, this review illustrates the need for increased clinical and genetic research on syndromes with obesity.

On the origin of obesity: identifying the biological, environmental and cultural drivers of genetic risk among human populations

“…Heritability estimates of obesity from twin and family studies range from 0.25 to 0.90 , suggesting a large portion of obesity risk may be because of inherited factors. To date, genetic association studies have identified 63, 12 and 157 loci involved in monogenic syndromic, monogenic non‐syndromic and polygenic forms of obesity, respectively .…”

Gain‐of‐function variants in the melanocortin 4 receptor gene confer susceptibility to binge eating disorder in subjects with obesity: a systematic review and meta‐analysis

“…Heritability estimates for BED and obesity range from 41% to 57% and from 25% to 90% . Multiple genes responsible for monogenic syndromic and non‐syndromic, oligogenic and polygenic forms of obesity have been identified . However, it is unclear as to which genes may predispose individuals to BED .…”

Obesity genetics and cardiometabolic health: Potential for risk prediction

“…These all have variable effects on body fat mass. Of the 79 forms of identified obesity syndromes, 19 have been fully elucidated, 11 have been partially elucidated, while 27 have been mapped to a chromosomal region but not characterized . Monogenic obesity presents as a rare condition, with severe obesity being attributable to recessive mutations coding for key metabolites in pathways for the hypothalamic control of appetite.…”

“…Of the 79 forms of identified obesity syndromes, 19 have been fully elucidated, 11 have been partially elucidated, while 27 have been mapped to a chromosomal region but not characterized. 14…”