Myelodysplastic syndromes are typically diseases of older adults. Early onset patients may have distinct molecular and clinical features or reflect a demographic continuum. The identification of differences between early onset patients and those diagnosed at a traditional age has the potential to advance understanding of the pathogenesis of myelodysplasia and may lead to formation of distinct morphologic subcategories. We studied a cohort of 634 patients with various subcategories of myelodysplastic syndrome and secondary acute myeloid leukemia, stratifying based on age at presentation and clinical parameters. We then characterized molecular abnormalities detected by next generation deep sequencing of 60 genes that are commonly mutated in myeloid malignancies. The number of mutations increased linearly with age and on average, patients >50 years of age had more mutations. TET2, SRSF2, and DNMT3A were more commonly mutated in patients >50 compared to patients ≤50. In general, patients >50 also had more mutations in spliceosomal, epigenetic modifier, and RAS gene families. Although there are age related differences in molecular features among patients with myelodysplasia, most notably in the incidence of SRSF2 mutations, our results suggest that patients ≤50 belong to a disease continuum with a distinct pattern of early onset ancestral events.