A toddler with a novel LEPR mutation

Abstract

There are numerous causes, such as environmental factors, medications, endocrine disorders, and genetic factors, that can lead to obesity. However, severe early-onset obesity with abnormal feeding behavior, mental retardation, dysmorphic features, organ-specific developmental abnormalities, and endocrine disorders suggest a genetic etiology. Mutations in genes related to the leptin-melanocortin pathway play a key role in genetic obesity. This pathway controls hypothalamic regulation of food intake. A few cases have been reported to have mutations in leptin (LEP) or leptin receptor (LEPR) genes. The cases had severe early-onset obesity, hyperphagia, and additional features, such as altered immune function, hypogonadism, and hypothyroidism. We present a 3-year-old male patient with severe early-onset obesity whose genetic analysis revealed a homozygous, novel, and pathogenic variant (c.1603+2T>C) in LEPR.

Keywords: Early-onset obesity; Leptin Receptor; Monogenic obesity; Mutation; Setmelanotide.