- Last edited on April 30, 2020
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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 populations, anywhere 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 age, with 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 ===== |