What is the pathophysiology of Down syndrome?

Updated: Apr 30, 2018
  • Author: Gratias Tom Mundakel, MBBS, DCH; Chief Editor: Maria Descartes, MD  more...
  • Print
Answer

Abnormal physiologic functioning affects thyroid metabolism and intestinal malabsorption. Patients with trisomy 21 have an increased risk of obesity. Frequent infections are presumably due to impaired immune responses, and the incidence of autoimmunity, including hypothyroidism and rare Hashimoto thyroiditis, is increased.

Patients with Down syndrome have decreased buffering of physiologic reactions, resulting in hypersensitivity to pilocarpine and abnormal responses on sensory-evoked electroencephalographic (EEG) tracings. Children with leukemic Down syndrome also have hyperreactivity to methotrexate.

Decreased buffering of metabolic processes results in a predisposition to hyperuricemia and increased insulin resistance. Diabetes mellitus develops in many affected patients. Premature senescence causes cataracts and Alzheimer disease. Leukemoid reactions of infancy and an increased risk of acute leukemia indicate bone-marrow dysfunction.

Children with Down syndrome are predisposed to developing leukemia, particularly transient myeloproliferative disorder and acute megakaryocytic leukemia. Nearly all children with Down syndrome who develop these types of leukemia have mutations in the hematopoietic transcription factor gene, GATA1. Leukemia in children with Down syndrome requires at least 3 cooperating events: trisomy 21, a GATA1 mutation, and a third, undefined genetic alteration.

Musculoskeletal manifestations in patients with Down syndrome include reduced height, atlanto-occipital and atlantoaxial hypermobility, and vertebral malformations of the cervical spine. These findings may lead to atlanto-occipital and cervical instability, as well as complications such as weakness and paralysis.

About 5% of patients with Down syndrome have GI manifestations, including duodenal atresia, Hirschsprung disease, and celiac disease. Many patients with trisomy 21 have otorhinolaryngologic manifestations, including hearing loss and recurrent ear infections. About 60% of patients have ophthalmic manifestations.

A study by Romano et al indicated that in persons with Down syndrome, brain cortical thickness is reduced with increasing age. The study involved 91 persons with Down syndrome, none of whom had dementia, with cortical thickness measured using magnetic resonance imaging (MRI). Frontal, temporal, parietal, and cingulate gyrus measurements showed bilateral cortical thinning in association with age, with thickness apparently declining more significantly and rapidly between the ages of 20 and 30 years. [13]

The American College of Obstetricians and Gynecologists (ACOG) has published pertinent guidelines on screening for fetal chromosomal abnormalities. [14]


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!