Down syndrome overview: Difference between revisions
No edit summary |
|||
| Line 25: | Line 25: | ||
== Epidemiology and Demographics == | == Epidemiology and Demographics == | ||
Down syndrome is the most common [[chromosomal]] abnormality. Each year approximately 3,000 to 5,000 children are born with this [[chromosome]] disorder and it is believed there are about 250,000 families in the United States of America who are affected by Down syndrome. [[Birth rate|Birth rates]] are highest among mothers of advanced [[maternal]] age however 80% of all children with Down syndrome are born to mothers younger than 35 years. Down syndrome occurs in people of all races and economic levels. | |||
== Risk Factors == | == Risk Factors == | ||
Revision as of 05:57, 21 March 2018
| https://https://www.youtube.com/watch?v=ze_6VWwLtOE%7C350}} |
|
Down syndrome Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Down syndrome overview On the Web |
|
American Roentgen Ray Society Images of Down syndrome overview |
|
Risk calculators and risk factors for Down syndrome overview |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Down syndrome is a genetic disorder caused by the presence of all or part of an extra 21st chromosome. Often Down syndrome is associated with some impairment of cognitive ability and physical growth as well as facial appearance. Down syndrome can be identified during pregnancy or at birth.
Historical Perspective
Down syndrome (Trisomey 21 or Dow's syndrome) is a genetic disorder is characterized by the presence of all or part of an extra 21st chromosome. John Langdon Down, a British doctor described it first in 1866. Jérôme Lejeune in 1959 ascribed the features associated with Down's syndrome to the presence of an extra 21st chromosome (trisomy 21). Based on anthropometric measurements and photographic appearance, John Landdon Down delineated a well-defined group of mentally disabled individuals, whose members all resembled the little girl very well. He called them, in concordance with the ethnical insights of the then famous dr. Blumenbach, mongoloid “idiots”. Today they are known by his own, more ethically correct name: Down's syndrome. Until the middle of the 20th century, the cause of Down syndrome was largely. However, was known that it affected humans of all races, was associated with older maternal age and was rare. Standard medical texts assumed it was caused by a combination of inheritable factors which had not been identified. Other theories focused on injuries sustained during birth. In 1886 Shuttleworth referred to Langdon Down's ethnic classification and he included the "Mongol type" in his publication. Beginning in 1888, John Langdon Down's work became widely accepted and was consistently being referred to by scientists and physicians, beginning with Goodheart in 1888. By the 20th century, Mongolism had become a widely used descriptive term. This was the title used by Bertram Hill in 1908 and by Penrose as late as 1961. With the discovery of karyotype techniques in the 1950s, it became possible to identify abnormalities of chromosomal number or shape. In 1959, Professor Jérôme Lejeune discovered that Down syndrome resulted from an extra chromosome. The extra chromosome was subsequently labeled as the 21st, and the condition as trisomy 21.
Pathophysiology
Down Syndrome (DS) is the consequence of trisomy of human chromosome 21 (Hsa21) and is the most common genetic form of intellectual disability. Additional copy of chromosome 21 results in elevated expression of many of the genes encoded on this chromosome, leading to variying expression of genes associated with this chromosome. Mechanisms leading to trisomy 21 include meiotic non-disjunction during meiosis I (majority) and meiosis II, Robertsonian translocation and mosaicism (rare). In addition, increased maternal age leads to rapid degradation of cellular proteins involved in spindle formation, sister chromatid cohesion and anaphase separation of sister chromatids in oocytes during cell cycle. Absence of chiasmata and suboptimally placed chiasmata are the major mechanisms involved in non-disjunction of chromosome 21.Immaturity of the feto-placental unit has been proposed as an explanation for the reduced maternal serum alpha fetoprotein (AFP) and unconjugated oestriol (UE3) levels and increased hCG levels in Down’s syndrome pregnancies. Reduced synthesis of AFP by the fetal liver is also thought to contribute to low AFP in Down’s syndrome pregnancies. Robertsonian translocation occurrs when the long arms of 2 acrocentric chromosomes (chromosomes with centromeres near their ends) fuse at the centromeres and the 2 short arms are lost. Mosaicism does not have any maternal association and it is a post-fertilization mitotic error. Disbilities found in Down syndrome patients are thought to arise secondary to varied genetic expression associated with the presence an extra 21st chromosome.
Causes
Down's syndrome (DS) is caused due to the presence of an extra 21st chromosome (triplication of chromosome 21). 95 percent of DS cases are due to meiotic non-disjunction during meiosis I. 4 percent of DS cases arise due to Robertsonian translocation and very rarely DS may be caused a post-fertilization mitotic error (mosaicism).
Differentiating Down syndrome from Other Diseases
The diagnosis of Down syndrome should be suspected in pre-natal assessment of fetuses on ultrasound examination. Second quad screen showing decreased alfa-fetoprotein (AFP) should raise the suspicion of fetal chromosomal abnormlaity. Pre-natal differentials of low AFP include Down syndrome, Edwards syndrome and Patau syndrome. In the newborn, Down syndrome should be differentiated from other congenital conditions presenting with hypotonia, poor feeding, poor growth and dysmorphic facial features. The differentials include isolated hypotonia, congenital hypothyroidism and Zellweger syndrome
Epidemiology and Demographics
Down syndrome is the most common chromosomal abnormality. Each year approximately 3,000 to 5,000 children are born with this chromosome disorder and it is believed there are about 250,000 families in the United States of America who are affected by Down syndrome. Birth rates are highest among mothers of advanced maternal age however 80% of all children with Down syndrome are born to mothers younger than 35 years. Down syndrome occurs in people of all races and economic levels.