Heredity plays an important role in childhood obesity: predisposing genetic factors are associated with the triggering effect of a favorable environment. The genes whose variants predispose to so-called polygenic obesity are:

-        FTO or fat mass and obesity-associated gene (16q12.2)

-        LEP or leptin (7q32.1)

-        LEPR or leptin receptor (1p31.1)

-        TNFα or tumor necrosis factor alpha (6p21.1-21.3)

-        MC4R or melanocortin 4 receptor gene (18q22)

-        ENPP1 or ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 or PC-1 human glycoprotein C1 (6q23.2)

-        PPARG or peroxisome proliferator-activated receptor gamma (3p25.2)

-        ACE or angiotensin-converting enzyme (17q23.3)

-        GST or glutathione S-transferase (6p12)

-        IL6 or interleukin-6 (7p15.3)

However, around 10 % of obesity is purely genetic (monogenic) in origin.

A distinction is made between

1) Syndromic obesity (see these terms)

- Prader-Willi syndrome

- Bardet-Biedle syndrome

- Alstrom syndrome

- Albright osteodystrophy

- WAGR syndrome

- biallelic mutation of the P4HTM gene:

       Very rare.  Biallelic heterozygosity of P4HTM gene mutations (3p21.3). Recently described syndrome associating hypotonia, mental retardation and obesity. Similar to HIDEA syndrome (see this term).

- 16p11.2 deletion

       This de novo deletion includes the SH2B1 gene. The SH2B1 protein plays an essential role in leptin-induced responses that activate JNK2-dependent and -independent mechanisms. SH2B1 also plays a regulatory role in the cascade of insulin-induced reactions, glucose homeostasis and insulin sensitivity. The results are hyperphagia, early-onset obesity, insulin resistance, below-average final adult height, delayed speech and language development, and a tendency to social isolation accompanied by aggressive behavior.

2) Non-syndromic genetic obesity

-        MC4R deficiency [MIM 618 406]

       Prevalence: 1 to 5/10,000. Causes 2 to 5 % of severe early-onset obesity. Autosomal dominant or recessive transmission of a loss-of-function mutation in the MC4R gene (18q22), coding for melanocortin receptor 4. Clinical manifestations are more severe in recessive forms (homozygosity). They are: hyperphagia, early morbid obesity, severe hyperinsulinism with accelerated growth and increased lean weight.

-        leptin deficiency [MIM 614 962]

       There are numerous pathological variants of the leptin gene (LEP or OB)(7q32.1), which may be symptomatic in the heterozygous (hyperphagia, early obesity) or homozygous (hyperphagia, early obesity, frequent infections, hypothyroidism, hypogonadotrophic hypogonadism) state. Blood leptin levels are very low, if not unmeasurable. Congenital leptin deficiency can be effectively treated with daily subcutaneous injections of recombinant human leptin.

-        leptin receptor deficiency [MIM 614 963].

       Rare. Autosomal recessive transmission of a mutation of the LEPR gene (1p31.3). Symptomatic patients are homozygous or composite heterozygotes (a different mutation on each allele). The phenotype is similar to leptin deficiency, but blood leptin levels are elevated. Precocious hyperphagia, lack of satiety, severe obesity. Hypogonadotrophic hypogonadism and pituitary insufficiency are often present.

-        POMC deficiency [MIM 176 830]

       Autosomal recessive transmission of a mutation of the POMC gene (2p23.3), coding for a pituitary pre-protein (pro-opiomelanocortin) that is the precursor of, among other things, a-MSH, is processed by PCSK1 and acts via MC4R. Hyperphagia, severe early-onset obesity, adrenal insufficiency, pale skin and red hair.

-        PCSK1 protein deficiency [MIM 600 955]

       PCSK1 (prohormone convertase 1) (5q15) protein deficiency causes severe diarrhea due to malabsorption in the neonatal period, postprandial hypoglycemia and early obesity. Some patients also present with diabetes insipidus, hypogonadotrophic hypogonadism, hypothyroidism and adrenal insufficiency. .

Anesthetic implications:

management of obesity and its comorbidities; checking pituitary hormones; hyperphagia may make compliance with preoperative fasting problematic.

References :

-        Sohn YB.
Genetic obesity: an update with emerging therapeutic approaches.
Ann Pediatr Endocrinol Metab 2022;27:169-75

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Childhood obesity and the anaesthetist.
Continuing Education in Anaesthesia, Critical Care & Pain 2012; 12 (4): 169-75

-        Callaghan LC, Walker JD.
An aid to drug dosing safety in obese children: development of a new nomogram and comparison with existing methods for estimation of ideal body weight and lean body mass.
Anaesthesia 2015; 70:176-82

-        Lejus C, Orliaguet G, Servin F, Dadure C, Michel F, Brasher C et al.
Peri-operative management of overweight and obese children and adolescents.
The Lancet Child & Adolescent Health 2017,1 : 311-22.

-        Marginean CO, Marginean C, Melit LE.
New insights regarding genetic aspects of childhood obesity: a minireview.
Front Pediatr 2018; 6: 271. doi: 10.3389/fped.2018.00271

-        Bhettay AZ.
Anaesthesia for the obese child.
Southern African Journal of Anaesthesia and Analgesia 2021; 27 (6 Suppl 1): S186-19

Updated: November 2023