Rett syndrome (RTT) is a rare, neurodevelopmental genetic disorder that develops in early childhood and influences many functions within neurobehavioural domains. The core of phenotype symptoms includes severe linguistic and motor impairments. The onset of RTT is characterised by a gradual or sudden loss of speech and hand function followed by a slow decrease in acquired gross motor skills with subsequent severe functional dependence. RTT is associated primarily with mutations in MECP2, a gene located on the long arm of the X chromosome (Xq28). The severity of impairments depends not only on genotype, but on the extent of X inactivation. However, CDKL5 and FOXg1 gene mutations have been also identified in girls affected by atypical RTT. Despite sharing neurological features, subjects with RTT present considerable clinical variability. Research on effects of genotype of RTT is expanding in many directions. The current chapter, will discuss the correlations between genotype and motor abilities in subjects with RTT. The main aim of this chapter is to relate functional outcomes, in particular motor impairments, to mutation type in patients with RTT. This chapter begins with a theoretical overview on genetic alterations in RTT and then focuses on motor specific impairments. In the second part of this chapter, we propose a preliminary research which analyzes the correlation between motor phenotype and specific genotype.