Introduction Leptin receptor also known as LEP-R, is a protein that in humans is encoded by the LEPR gene. LEP-R has also been designated as CD295. Leptin receptors are known to be important in regulating body weight. They are highly expressed in areas of the hypothalamus, as well as in T-lymphocytes, and vascular endothelial cells. Leptin receptor deficiency is a congenital disorder caused by homozygous mutation of LEPR gene, on chromosome 1p31. The mutation could be either missense, nonsense, or frameshift. There is high association with consanguinity. Major symptoms include severe obesity, hyperphagia, and its association with increased susceptibility to Entamoeba Hystolytica infection. Other symptoms include hypogonadism, impulsivity, stubborness, and impaired T-cell mediated immunity. There is also association with seizures. Psychologically patients may show emotional lability and social disability, but no mental retardation. Case report A 4 year 10 months old boy was diagnosed with leptin-receptor deficiency at SickKids at age of 1 year. Patient presented with hyperphagia and weight gain. Past history includes febrile seizures between the ages of 1–1.5 years, during teething phase. Shaking spells lasted over 5 min with eyes rolling up and drooling. Patient was born full-time after prolonged labour by C-section. Birth weight was 7 lb, and 6 oz. Patient had increased appetite, which led to referral to SickKids Genetic Metabolic Service. Parents had to lock up the refrigerator and cupboards of food to avoid food stealing. Patient is on RYG diet, as well as on Topiramate and Sertraline. The patient had normal developmental milestones. Weight at 4 year 10 month of age was 30.5 kg. Height of 107.5 cm, with head circumference of 50.6 cm. A 22-channel EEG with polygraphic recording of EMG, EOG, and EKG was performed in regards to febrile seizures. Results Patients EEG was moderately abnormal. There was an active epileptiform focus in the left frontocentral region, on two occasions triggering right partial motor seizure activity. Discussion This case of leptin receptor deficiency is unique for neurophysiologic studies, including EEG studies performed. Leptin reduces excitability in some hypothalamic neurons via leptin receptor activation of the JAK2 and PI3K intracellular signaling pathways. Whereas mutation of LEPR gene results in abnormal splicing of leptin-receptor transcripts, and generates a mutant leptin receptor that lacks both transmembrane and intracellular domains. In this patient, there is a high probability that a lack of JAK2 and PI3K activation caused neuronal excitation in the hypothalamus, which activated seizure activity. Hypothalamus has high association with gelastic seizures, but more studies need to be done to determine the exact correlation between leptin receptor deficiency and seizure activity. Perhaps with more potential cases and continued research, we will eventually better understand the connection between leptin receptors and its hormones in the hypothalamus.