Down Syndrome Essay

Down Syndrome (DS) is a chromosomal disease affecting tens of thousands of individuals. DS is responsible for a wide range of health disorders, including, but not limited to, congenital heart disease, cancers, Alzheimer’s, and other phenotypic abnormalities (Asim et al., 2015). Given its relatively high prevalence (1 in 900 births) in some locations, the impact of DS is high (Shin et al., 2009). Trisomy 21, Mosaic Down Syndrome, and Translocation Down Syndrome are three instances of abnormalities in chromosome 21 replication. At 95% prevalence among DS patients, Trisomy 21 is the possession of a third 21st chromosome causes the genes present to be expressed at different rates compared to non-DS cohorts.
Human chromosome 21 (HSA21) failure to segregate during oocyte meiosis I, also known as nondisjunction, is the leading cause of DS. The result of nondisjunction is aneuploidy. Evidence supports nondisjunction in HSA21 of oocytes increases with increasing age due to single or absent segregation in the telomeric region, or spindle malfunction (Oliver et. al, 2008). Spindle formation has been shown to
be impeded by pH changes in oocyte brought on by poor circulation to follicle, leading to nondisjunction (Gaulden, 1992). Without proper pH levels, proteins are not able to function normally. However, given the complexity of the disease, other underlying mechanisms have been identified both in the formation of trisomy 21 and in its clinical implications.
The pericentrin gene (PCNT) has been implicated in its role in Down Syndrome. The PCNT encoded protein, pericentrin, is responsible for proper centrosome function during cell cycle. The long α helix of pericentrin protein provides a platform for microtubulin nucleation along with γ tubulin (Doxsey et al. 1994; Hinchcliffe et al., 2001). The implications of PCNT over-expression were suggested to be disruption of chromosome separation during embryonic development. PCNT was found to be expressed in 72% of subjects at double the rate compared to non-DS cohorts (Salemi et al., 2013). PCNT over-expression found in Down Syndrome patients helps to explain its comorbidity with a host of other diseases.
Diseases and clinical conditions often associated with Down Syndrome include early onset Alzheimer’s Disease, Leukemia, atrioventricular defects, and gastrointestinal stenosis and obstructions.
General mechanisms of these diseases were outlined by Asim, et al. Cardiac defects arise from septal deformations caused by failure of cell adhesions. GI obstruction is the direct result of absence of myenteric innervation in the colon. The lack of innervation causes drop in neurotransmitters necessary for proper contraction and resulting peristaltic movement. The prevalence of blood disorders is associated with mutations in the GATA-1 gene that is involved in blood cell differentiation. Studies by Kyttala et al., (1994) showed Down Syndrome Critical Region 1, a hematological negative-feedback regulator, overexpression impairs downstream regulation of blood cell
differentiation.
Neurological deficits arise from over-expression of amyloid precursor protein (APP), beta secretase 2, Phosphatidylionositol binding clathrin assembly protein, and Apoliopoprotein E leading to degeneration of neural tissue. Beta secretase 2 is responsible for proteolytic cleavage of APP, resulting in neural plaque aggregation and deposition (Kocki et al., 2014). Such mechanisms can help explain the mental deficiencies present in DS patients.