Problems in mathematics are a frequent major complaint in neuropediatric departments, for which there are two explanatory theoretical models: the hypothesis of a genetic and modular origin (with a number sense deficit) and a multidetermined origin. The purpose of this paper is to review the mathematical difficulties described in Turner syndrome and Fragile X syndrome, because a specific mathematical disorder is usually reported in these populations, supporting the existence of a number sense. Analysis of the literature reveals highly variable cognitive phenotypes in these populations, especially regarding mathematical abilities. Performance heterogeneity might be related to different factors such as the abilities needed to perform the task, the variability of definitions, the different tests used in the studies and the heterogeneity of the syndromes themselves. A number sense deficit is usually described in these syndromes, but variable cognitive impairments are also observed. The idea of a modular functioning is then debated and we argue for the necessity of a global cognitive evaluation approach.