Down Syndrome

Abstract

Down syndrome (DS) is the most common genetic cause of significant intellectual disability in humans. It was one of the first chromosomal disorders of humans to be associated with intellectual disabilities and, as such, has provided an evidence-based foundation from which work on many different disorders has been launched. John Langdon Down first described this syndrome in 1866 using the term mongoloid idiocy. The initial clinical description of DS comprised physical features (e.g., epicanthal folds, flat and broad face, enlarged tongue, microcephaly, short stature) and cognitive characteristics (e.g., intellectual impairment, fine and gross motor coordination problems, poor speech articulation). He also described a relatively positive personality in these individuals. Contemporary topographical descriptions are remarkably similar to Down’s description nearly 150 years ago, but a variety of other healthrelated issues have been uncovered since that time including congenital cardiac abnormalities, hypotonia, hearing and visual impairments, hypothyroidism, and precocious aging (Rasmussen, Whitehead, Collier, and Frias 2008). In accordance with the core tenets of this text, in this chapter we discuss epidemiology, etiology, and what is known about core pathophysiological mechanisms in DS; neurological abnormalities, including contemporary findings in neuroimaging; neurocognitive and socialbehavioral manifestations; and emergent evidencebased treatment efforts. The chapter concludes with a brief discussion of the phenotype-genotype linkages for DS, and a review of the priorities set by a national panel of experts in DS (Rasmussen et al. 2008). When compared to other congenital abnormalities, DS represents one of the most common disorders. Contemporary prevalence estimates indicate the occurrence of DS in approximately 9.0–11.8 (Shin et al. 2009) to 13.66 (Canfield et al. 2006) per 10,000 live births. The rate of infants born with DS also has a strong relationship with increasing maternal age. For example, a 20-year-old mother has a 1 in 1,923 chance of giving birth to an infant with Down syndrome, whereas the chance for a 49-year-old mother is 1 in 12 (Prescott 1988). The cause of this phenomenon, however, is not well understood (Lamb and Hassold 2004).