BackgroundSeveral mechanisms have been suggested for obesity in Down syndrome. Aim of the studyAssessment of serum levels of leptin, insulin like growth factor-I (IGF-I), thyroid stimulating hormone (TSH) and free thyroxin (FT4) in a prepubertal Egyptian sample of children with DS compared to their age and sex matched healthy controls and sibs of some of them. Subjects and methodsA prospective case control study was conducted on 80 children, classified as follows: Groups I & II: enrolled 20 cases with DS for each, sibs were studied only for group I, Group III: 20 healthy siblings of group I, and Group IV: 20 healthy controls. Anthropometric measurements, serum leptin, IGF-1, TSH, and FT4 assessment using enzyme linked immuno-sorbent assay (ELISA) were carried out for all studied children. ResultsDS children whether with studied sibs or without studied sibs had significantly higher mean values of leptin levels compared to sibs of group I & IV (P=0.0001 for all). Meanwhile, mean values of IGF-I showed statistically insignificant differences between all studied groups (p>0.05 for all). Studied DS children whether with studied sibs or without studied sibs had significantly higher mean values of TSH levels compared to sibs of group I and controls (P=0.0001 for all). Mean values of FT4 were significantly higher in enrolled DS without their studied sibs compared to sibs of group I (p=0.01), while mean values of FT4 were significantly lower in sibs of group I compared to controls (p=0.001). ConclusionSerum leptin levels were significantly higher in studied DS children compared to both studied sibs and healthy controls and they were also positively correlated with BMI in studied DS children and their sibs highlighting a possible role of body fat% and leptin values in the pathogenesis of obesity in DS children.