Neurological and neurodevelopmental manifestations in children and adolescents with Down syndrome

Down syndrome (DS) is a common genetic condition that is associated with a wide range of medical and developmental challenges, including neurological and neurodevelopmental conditions. DS is caused by three copies of chromosome 21 and is the most common genetic cause of intellectual disability (ID). Beyond ID, individuals with DS may also manifest many characteristic medical, neurological, neurobehavioral, and developmental conditions that are complex and result in a variety of clinical presentations with varying etiologies, diagnostic strategies, and interventions. In this clinical review, we present an overview of neurobiology in DS and potential pharmacological targets that may impact the characteristic developmental, cognitive, and learning profile seen in DS. We examine medical conditions that may impact development and functioning as well as neurologic findings such as hypotonia and motor impairments, epilepsy, and abnormal movements. Finally, we extensively discuss the nuances of behavioral, neurodevelopmental, and mental health conditions that may co-occur in children and adolescents with DS and may sometimes be misattributed to manifestations of ID alone. This chapter seeks to draw attention to these conditions that necessitate keen diagnostic discernment, specialized evaluation and treatment, and further research to better inform clinical care.