Obesity in children: inheritance and treatment – state of art 2024

Inheritance

For a couple of decades, we have faced the pandemic of obesity, both in children and adults. Recent statistics have revealed that 39 million of children younger than 5 years and 340 million older children are affected by excessive weight. Moreover, a disturbing trend in BMI is observed, with the index increasing by 0.32 kg/m2 per decade. Observational follow-up studies reveal that childhood obesity is associated with a 5.8-fold higher risk of obesity in adulthood compared to normal body weight in childhood [1]. Fifty-five per cent of children who have obesity in childhood remain obese in their teens, and 70% are obese after the age of 30 years. Among teenagers, the statistics are even more serious. As many as 80% of teenagers with obesity retain obesity as adults [2]. Those persons are at risk of comorbidities and complications of obesity. Not only is cardiometabolic risk significantly higher, but also, among others, the incidence of cancer, infertility, emotional and depressive disorders are increased. And this is not the end of the story because obesity increases the risk of excessive weight gain and metabolic complications in the offspring.
It is well known that children with obesity often have parents with obesity, and obesity often ‘runs in’ these families. The risk of obesity in a child is almost two-fold higher if the parents are obese or overweight [3]. It looks even worse if both parents are obese (OR: 12.0) or severely obese (OR: 22.3) [4]. Usually, in each family, there are several reasons for obesity „heritability”. Non-modifiable factors related to obesity persistence in families are mutations in obesity-related genes. It is estimated that 40–75% of BMI and abdominal adiposity are attributable to independent genetic influences [5]. Very rare causes of multigenerational obesity are autosomal-dominant pathogenic mutations in some genes where obese phenotype in observed in heterozygous patients. The mutations in the melanocortin-4 receptor (MC4R), detected in 3–5% of severely obese patients, are the most common form of genetic obesity; what is more, their inheritance is autosomal-dominant [6]. Most of the monogenic and syndromic forms of obesity are inherited in autosomal-recessive manner and the family history of obesity is not characteristic. Polygenic heritability of obesity is much more common, determined by the cumulative effect of risk variants in multiple genes related to hunger/ satiety pathways,...


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