Table 2.

Most Common Forms of Non-Syndromic Monogenic Obesity [49, 60]

Gene	Mutation(s)	Prevalence	Phenotypes	Genetic Testing for Diagnosis
MC4R	Homozygous, Compound heterozygous, Heterozygous	3–5% of children with early-onset severe obesity	Hyperphagia, Early-onset obesity, Increased linear growth and height, Increased bone mass, Increased fat and lean mass	Direct sequencing of MC4R
LEP	Homozygous	27 patients reported	Severe hyperphagia, Incapacity of feeling satiety, Early-onset obesity, Hypogonadotropic hypogonadism, Hypothalamic hypothyroidism with puberty delay, Reduced adult height, Increased risk of infections	Direct sequencing of LEP
LEPR	Homozygous, Compound heterozygous	3% of children with severe obesity from a cohort enriched in consanguineous families	Severe hyperphagia, Incapacity of feeling satiety, Early-onset obesity, Hypogonadotropic hypogonadism, Hypothalamic hypothyroidism with puberty delay, Reduced adult height, Increased risk of infections, Increased bone mineral density	Direct sequencing of LEPR
POMC	Homozygous, Compound heterozygous	11 patients reported	Neonatal adrenal insufficiency, Early-onset obesity, Hyperphagia, Central hypothyroidism, Gonadotropin deficiency	Direct sequencing of POMC
PCSK1	Homozygous, Compound heterozygous	19 patients reported	Hyperphagia, Obesity, Intestinal dysfunction, Postprandial hypoglycemia, Central hypothyroidism, Hypogonadotropic hypogonadism, Diabetes insipidus	Direct sequencing of PCSK1