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child:genetic-disorders:down-syndrome-trisomy-21 [on May 20, 2019]
child:genetic-disorders:down-syndrome-trisomy-21 [on March 3, 2021] (current)
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 == Epidemiology == == Epidemiology ==
-The prevalence ​varies ​in different populationsanywhere from 1 in 319 to 1 in 1000 births.[([[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC4464633/​|Asim,​ A., Kumar, A., Muthuswamy, S., Jain, S., & Agarwal, S. (2015). Down syndrome: an insight of the disease. Journal of biomedical science, 22(1), 41.]])] ​The incidence ​of Down syndrome ​increases significantly with maternal ​age.+  * Typically, below the age of 10, individuals with Down syndrome are cheerful, placid, cooperative,​ and adapt easily at home.[(Sadock,​ B. J., Sadock, V. A., & Ruiz, P. (2015). Kaplan & Sadock'​s synopsis of psychiatry: Behavioral sciences/​clinical psychiatry (Eleventh edition.). Philadelphia:​ Wolters Kluwer.)] 
 +    * When adolescence is reached, however, social, emotional, and behavioural difficulties begin to emerge, and there is also an increased risk for psychotic disorders.[(Sadock,​ B. J., Sadock, V. A., & Ruiz, P. (2015). Kaplan & Sadock'​s synopsis of psychiatry: Behavioral sciences/​clinical psychiatry (Eleventh edition.). Philadelphia:​ Wolters Kluwer.)] 
 +  * The average ​prevalence ​of Down syndrome is 1 in 700 individuals 
 +  * The risk for having an offspring with Down syndrome varies; it generally is much lower with younger maternal agewith a 1 in 1500 chance in women age <20. In women older than 45 years old the risk is 1 in 25.[([[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC4464633/​|Asim,​ A., Kumar, A., Muthuswamy, S., Jain, S., & Agarwal, S. (2015). Down syndrome: an insight of the disease. Journal of biomedical science, 22(1), 41.]])] 
 + 
 +== Prognosis == 
 +  * It is the most common viable chromosomal disorder, and most individuals are able to survive into adulthood. 
 +  * Around 75% of adults with Down syndrome ​survive to age 50, and 25% will survive to age 60. 
 +  * A core feature of aging in Down syndrome is the progressive accumulation of [[geri:​dementia:​alzheimers|Alzheimer'​s]] brain pathology including senile plaques and neurofibrillary tangles. Almost all individuals will have these findings by age 40.[([[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC4184282/​|Head,​ E., Powell, D., Gold, B. T., & Schmitt, F. A. (2012). Alzheimer'​s Disease in Down Syndrome. European journal of neurodegenerative disease, 1(3), 353–364.]])]
  
 == Comorbidity == == Comorbidity ==
-Down syndrome ​is also associated with an increased ​risk of developing early onset [[geri:dementia:​alzheimers|Alzheimer'​s ​disease]].+  * Individuals with Down syndrome ​have a significantly higher ​risk for developing early-onset Alzheimer'​s dementia.[([[https://​pubmed.ncbi.nlm.nih.gov/​12431254/​|Glasson, E. J., Sullivan, S. G., Hussain, R., Petterson, B. A., Montgomery, P. D., & Bittles, A. H. (2002). The changing survival profile of people with Down'​s ​syndrome: implications for genetic counselling. Clinical genetics, 62(5), 390–393.]])] 
 +    * By age 40, up to 33% of individuals have a clinical diagnosis of dementia.[([[https://​pubmed.ncbi.nlm.nih.gov/​22844278/​|Head,​ E., Silverman, W., Patterson, D., & Lott, I. T. (2012). Aging and down syndrome.]])] The incidence is as high as 77% by age 60.
  
 +== Risk Factors ==
 +  * Advanced maternal age is a risk factor for the ofspring being born with Down Syndrome.[([[https://​pubmed.ncbi.nlm.nih.gov/​19050929/​|Allen,​ E. G., Freeman, S. B., Druschel, C., Hobbs, C. A., O’Leary, L. A., Romitti, P. A., ... & Sherman, S. L. (2009). Maternal age and risk for trisomy 21 assessed by the origin of chromosome nondisjunction:​ a report from the Atlanta and National Down Syndrome Projects. Human genetics, 125(1), 41-52.]])]
 ===== Diagnosis ===== ===== Diagnosis =====
 +<callout icon="​fa fa-lightbulb-o"​ type="​success"​ title="​Mnemonic">​
 +The mnemonic the ''​**5 A'​s**''​ of Down Syndrome can be used to remember the features associated with Down syndrome.
 +\\
 +  * ''​**A**''​ - Advanced maternal age
 +  * ''​**A**''​ - [[geri:​dementia:​alzheimers|Alzheimer'​s disease]] (early)
 +  * ''​**A**''​ - Acute Myeloid Leukaemia (AML)/Acute lymphocytic leukemia (ALL)
 +  * ''​**A**''​ - Atrioventricular septal defects
 +  * ''​**A**''​ - Atresia (duodenal)
 +</​callout>​
 ===== Pathophysiology ===== ===== Pathophysiology =====
-In the majority of cases, Down syndrome is not hereditary.+  * In the majority of cases, Down syndrome is not hereditary
 +  * 95% of cases are due to meiotic nondisjunction secondary to increased risk from maternal ageing. A minority (4%) of cases due to unbalanced Robertsonian translocation,​ usually between chromosomes 14 and 21. Even more rarely, about 1% of cases are due to post-fertilization mitotic errors.
  
  
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   * [[https://​www.ncbi.nlm.nih.gov/​pubmed/​17389125|Visootsak,​ J., & Sherman, S. (2007). Neuropsychiatric and behavioral aspects of trisomy 21. Current psychiatry reports, 9(2), 135-140.]]   * [[https://​www.ncbi.nlm.nih.gov/​pubmed/​17389125|Visootsak,​ J., & Sherman, S. (2007). Neuropsychiatric and behavioral aspects of trisomy 21. Current psychiatry reports, 9(2), 135-140.]]
 ===== Investigations ===== ===== Investigations =====
 +  * Prior to birth, on first-trimester ultrasound will show nuchal translucency and hypoplastic nasal bone
 +  * Maternal serum will show elevated hCG and inhibin.[([[https://​pubmed.ncbi.nlm.nih.gov/​9091018/​|Noble,​ P. L., Wallace, E. M., Snijders, R. J. M., Groome, N. P., & Nicolaides, K. H. (1997). Maternal serum inhibin‐A and free β‐hCG concentrations in trisomy 21 pregnancies at 10 to 14 weeks of gestation. BJOG: An International Journal of Obstetrics & Gynaecology,​ 104(3), 367-371.]])]
 +===== Physical Exam =====
 +On examination,​ individuals will have:
 +  * Intellectual disability, flat facies, prominent epicanthal folds
 +  * Examination of the hands shows a single palmar crease, incurved fifth finger, and a gap between the first two toe digits
 +  * Cardiovascular:​ atrial septal defect, congenital heart disease
 +  * Gastrointestinal:​ duodenal atresia, Hirschsprung disease
 ===== Treatment ===== ===== Treatment =====
 ===== Resources ===== ===== Resources =====