Two Siblings with Mutation in the Leptin Receptor Gene

Monogenic obesity is a rare cause of obesity. Mutations in the orectic or anorectic pathways are the important reasons of monogenic obesity. We present here two siblings with mutation in the leptin receptor gene (LEPR). A male patient was evaluated with the cause of obesity. On admission, he was 1.9 decimal age and his anthropometric measures were as follows: weight 28.2 kg [+6.49 standard deviation score (SDS)], height 81.9 cm (-1.01 SDS), and body mass index (BMI) 42.04 kg/m2 (+8.1 SDS). His birth weight was 3700 g. The parents were healthy and non-consanguineous. The patient had a history of rapid weight gain and over-nutrition after birth. There were anxiety attacks when access to food was restricted. He had a sister with similar symptoms. On physical examination, the patient had significant obesity and o-bain deformity; the rest of the systemic examination was normal. His external genitalia were at Tanner stage I with no axillary hair. His sister was evaluated with similar complaints. On admission, she was 6.5 decimal age and her anthropometric measures were as follows: 58.7 kg (+5.13 SDS), height 125 cm (+1.43 SDS), and BMI was 35.57 kg/m2 (+3.93 SDS). Her birth weight was 4050 g. There was a history of gestational diabetes mellitus during pregnancy. The patient had a history of rapid weight gain and over-nutrition after birth similar to her brother. She was in primary school at the admission, and her school performance history was normal. Her physical examination was normal, except obesity, and she was pre-pubertal. Both siblings had normal mental-motor development according to their age. We suspected secondary or pathological obesity because of the severe infantile-onset obesity in both cases. Patients' serum leptin levels were significantly higher. Genetic investigation revealed that both patients had a mutation in the LEPR gene. LEPR mutation is a rare disorder and was described in small number of families in the literature. Monogenic obesity should be kept in mind in patients with severe infantile-onset obesity. LEPR mutations can be detected only by molecular genetic analysis in suspected patients.