Down syndrome is a genetic disorder caused by trisomy of all or part of chromosome 21. Characteristic facial features include mild microcephaly, upslanting palpebral fissures, small nose with flat nasal bridge, small ears, and epicanthal folds. Other physical features include hypotonia, short neck with loose skin folds, single palmar creases, wide gap between first and second toes ("sandal gap"), and short stature. The degree of intellectual disability is variable.

Patients are at greater risk for atlantoaxial instability, hypothyroidism, constipation, gastroesophageal reflux disease, congenital heart disease, leukemia, impaired immune system, obstructive sleep apnea, hearing deficits, vision loss, seizures, dysphagia, pulmonary hypertension, type 1 diabetes, alopecia, celiac disease, juvenile idiopathic arthritis, vitiligo, and Alzheimer disease pathology / early-onset dementia. Life expectancy is 58.6 years. Major causes of mortality are congenital heart disease (in early childhood) and respiratory infections (in childhood and adulthood).