Williams (WS) and Down (DS) syndromes are neurodevelopmental disorders with distinct genetic origins and different spatial memory profiles. In real-world spatial memory tasks, where spatial information derived from all sensory modalities is available, individuals with DS demonstrate low-resolution spatial learning capacities consistent with their mental age, whereas individuals with WS are severely impaired. However, because WS is associated with severe visuo-constructive processing deficits, it is unclear whether their impairment is due to abnormal visual processing or whether it reflects an inability (...) to build a cognitive map. Here, we tested whether blindfolded individuals with WS or DS, and typically developing (TD) children with similar mental ages, could use path integration to perform an egocentric homing task and return to a starting point. We then evaluated whether they could take shortcuts and navigate along never-traveled trajectories between four objects while blindfolded, thus demonstrating the ability to build a cognitive map. In the homing task, 96% of TD children, 84% of participants with DS and 44% of participants with WS were able to use path integration to return to their starting point consistently. In the cognitive mapping task, 64% of TD children and 74% of participants with DS were able to take shortcuts and use never-traveled trajectories, the hallmark of cognitive mapping ability. In contrast, only one of eighteen participants with WS demonstrated the ability to build a cognitive map. These findings are consistent with the view that hippocampus-dependent spatial learning is severely impacted in WS, whereas it is relatively preserved in DS. (shrink)