The importance of genetic and chromosomal abnormalities lies in their interference with normal development, leading to various impairments. In this chapter, genetic and chromosomal syndromes resulting in human disabilities are explained. It investigates the way alterations in genes or chromosomes disrupt normal development to cause other physical, cognitive, and functional impairments. The chapter discusses the different forms of genetic mutation and chromosome abnormalities that are commonly associated with disability. It also emphasizes the significance of inheritance patterns and genetic counselling. This chapter will clarify the way people who have genetic and chromosomal syndromes usually experience challenges in the social environment. These obstacles also cause emotional and financial strains on families taking care of them.