pediatrics
Down Syndrome (Trisomy 21)
Pathophysiology of Down Syndrome
As with most conditions that result from chromosome imbalance, Down syndrome affects multiple systems and causes both structural and functional defects (see table). Not all defects are present in each person. Most affected people have some degree of cognitive impairment, ranging from severe (IQ 20 to 35) to mild (IQ 50 to 75). Gross motor and language delays also are evident early in life. Height is often reduced, and there is an increased risk of obesity. Approximately 50% of affected neonates have congenital heart disease; Ventricular Septal Defect (VSD) and atrioventricular canal defect (endocardial cushion defect) are most common ( Approximately 6% of affected people have gastrointestinal anomalies, particularly Duodenal atresia , sometimes along with Many people develop endocrinopathies, including thyroid disease (most often Hypothyroidism in Infants and Children ) and Atlanto-occipital and atlantoaxial hypermobility, as well as bony anomalies of the cervical spine, can cause atlanto-occipital and cervical instability; weakness and paralysis may result. Approximately 60% of people have eye problems, including Congenital Cataract , Most people have Hearing Loss , and ear infections are very common. The aging process seems to be accelerated ( Pathophysiology references ). In recent decades, the median life expectancy has increased to about 60 years, and some affected people live into their 80s ( Affected women have a 50% chance of having a fetus that also has Down syndrome; however, there appears to be an increased risk of Spontaneous Abortion . Men with Down syndrome are infertile, except for those with mosaicism. 1.Irving CA, Chaudhari MP: Cardiovascular abnormalities in Down's syndrome: Spectrum, management and survival over 22 years.Arch Dis Child97(4):326-330, 2012. doi: 10.1136/adc.2010.210534 2.de Groot-van der Mooren MD, Scheerman BC, Rammeloo LAJ, et al: Neonatal mortality and morbidity in Down syndrome in the time of prenatal aneuploidy testing: A retrospective cohort study.Eur J Pediatr182(1):319-328, 2023. doi: 10.1007/s00431-022-04686-3 3.Stoll C, Dott B, Alembik Y, Roth MP: Associated congenital anomalies among cases with Down syndrome.Eur J Med Genet58(12):674-680, 2015. doi: 10.1016/j.ejmg.2015.11.003 4.Horvath S, Garagnani P, Bacalini MG, et al: Accelerated epigenetic aging in Down syndrome.Aging Cell14(3):491-495, 2015. doi: 10.1111/acel.12325 5.Englund A, Jonsson B, Zander CS, et al: Changes in mortality and causes of death in the Swedish Down syndrome population.Am J Med Genet A161A(4):642-649, 2013. doi: 10.1002/ajmg.a.35706 6.Davidson YS, Robinson A, Prasher VP, Mann DMA: The age of onset and evolution of Braak tangle stage and Thal amyloid pathology of Alzheimer's disease in individuals with Down syndrome.Acta Neuropathol Commun6(1):56, 2018. doi: 10.1186/s40478-018-0559-4 7.Kucik JE, Shin M, Siffel C, Marengo L, Correa A; Congenital Anomaly Multistate Prevalence and Survival Collaborative: Trends in survival among children with Down syndrome in 10 regions of the United States.Pediatrics131(1):e27-e36, 2013. doi: 10.1542/peds.2012-1616 8.Santoro SL, Esbensen AJ, Hopkin RJ, et al: Contributions to Racial Disparity in Mortality among Children with Down Syndrome.J Pediatr174:240-246.e1, 2016. doi: 10.1016/j.jpeds.2016.03.023 