downs syndrome Resources | downs syndrome, characteristics of downs syndrome

Individuals with Down syndrome have lower than average cognitive ability, normally ranging from mild to moderate retardation. Some individuals may have average intelligence overall, but will generally have some amount of developmental disability, such as a tendency toward concrete thinking or naïveté. There is also a small number of individuals with Down syndrome with severe to profound mental retardation. The incidence of Down syndrome is estimated at 1 per 800 to 1 per 1000 births.

The common physical features of Down syndrome also appear in people with a standard set of chromosomes. They include a simian crease (a single crease across one or both palms), almond shaped eyes, shorter limbs, speech impairment, and an enlarged tongue. Health concerns for individuals with Down syndrome include a higher risk for congenital heart defects, gastroesophageal reflux disease, recurrent ear infections, obstructive sleep apnea, and thyroid dysfunctions.

Early childhood intervention, screening for common problems, medical treatment where indicated, a conducive family environment, and vocational training can improve the overall development of children with Down syndrome. While some of the genetic limitations of Down Syndrome cannot be overcome, education and proper care, initiated at any time, can improve quality of life.^[1]

Characteristics

Individuals with Down syndrome may have some or all of the following physical characteristics:^[2] oblique eye fissures with small skin folds on the inner corner of the eyes, muscle hypotonia, a flat nasal bridge, a single palmar fold (simian crease), a large and protruding tongue, a short neck, white spots on the iris, excessive flexibility in joints, congenital heart defects, excessive space between large and second toe, and a single flexion furrow of the fifth finger. Most individuals with Down syndrome have mental retardation in the mild (IQ 50–70) to moderate range (IQ 35–50),^[3] with scores for children with Mosaic Down syndrome (explained below) some 10–30 points higher.^[4] In addition, individuals with Down syndrome can have serious abnormalities affecting any body system.

Genetics

Down syndrome is a chromosomal abnormality characterized by the presence of an extra copy of genetic material on the 21st chromosome, either in whole (trisomy 21) or part (such as due to translocations). The effects of the extra copy varies greatly from individual to individual, depending on the extent of the extra copy, genetic background, environmental factors, and random chance. Down syndrome occurs in all human populations, and analogous effects have been found in other species such as chimpanzees and mice. Recently, researchers have been able to create transgenic mice with most of human chromosome 21 (in addition to the normal mouse chromosomes). People with Down Syndrome often have a simian crease on the palmar surface of the hand.^[5] The extra chromosomal material can come about in several distinct ways. A normal human karyotype is designated as 46,XX or 46,XY, indicating 46 chromosomes with an XX arrangement for females and 46 chromosomes with an XY arrangement for males.^[6]

Trisomy 21

Trisomy 21 (47,XX,+21) is caused by a meiotic nondisjunction event. With nondisjunction, a gamete (i.e., a sperm or egg cell) is produced with an extra copy of chromosome 21; the gamete thus has 24 chromosomes. When combined with a normal gamete from the other parent, the embryo now has 47 chromosomes, with three copies of chromosome 21. Trisomy 21 is the cause of approximately 95% of observed Down syndromes, with 88% coming from nondisjunction in the maternal gamete and 8% coming from nondisjunction in the paternal gamete.^[7]

Mosaicism

Trisomy 21 is generally caused before conception, and all cells in the body are affected. However, when some of the cells in the body are normal and other cells have trisomy 21, it is called Mosaic Down Syndrome (46,XX/47,XX,+21).^[8] This can occur in one of two ways: A nondisjunction event during an early cell division in a normal embryo leads to a fraction of the cells with trisomy 21; or a Down syndrome embryo undergoes nondisjunction and some of the cells in the embryo revert back to the normal chromosomal arrangement. There is considerable variability in the fraction of trisomy 21, both as a whole and among tissues. This is the cause of 1–2% of the observed Down syndromes.^[7] There is evidence that mosaic Down syndrome may produce less developmental delay, on average, than full trisomy 21.^[9]

Robertsonian translocation

The extra chromosome 21 material that causes Down syndrome may be due to a Robertsonian translocation. In this case, the long arm of chromosome 21 is attached to another chromosome, often chromosome 14 (45,XX,t(14;21q)) or itself (called an isochromosome, 45,XX,t(21q;21q)). Normal disjunction leading to gametes have a significant chance of creating a gamete with an extra chromosome 21. Translocation Down syndrome is often referred to as familial Down syndrome. It is the cause of 2-3% of the observed Down syndromes.^[7] It does not show the maternal age effect, and is just as likely to have come from fathers as mothers.

Duplication of a portion of chromosome 21

Rarely, a region of chromosome 21 will undergo a duplication event. This will lead to extra copies of some, but not all, of the genes on chromosome 21 (46,XX,dup(21q)).^[10] If the duplicated region has genes that are responsible for Down syndrome physical and mental characteristics, such individuals will show those characteristics. This cause is very rare and no rate estimates are possible.

Epidemiology

The incidence of Down syndrome is estimated at 1 per 800 to 1 per 1000 births.^[12] In 2006, the Center for Disease Control estimated the rate as 1 per 733 live births in the United States (5429 new cases per year).^[13] Approximately 95% of these are trisomy 21, making it the most common human aneuploidy. Down syndrome occurs in all ethnic groups and among all economic classes.

Maternal age influences the risk of conceiving a baby with Down syndrome. At maternal age 20 to 24, the risk is 1/1490, while at age 40 the risk is 1/106, and at age 49 the risk is 1/11.^[14] Although the risk increases with maternal age, 80% of children with Down syndrome are born to women under the age of 35,^[15] reflecting the overall fertility of that age group. Other than maternal age, no other risk factors are known. However, in up to 12% of trisomy 21 cases, the extra chromosome comes from the paternal gamete.^[16] There does not appear to be a paternal age effect.

Many standard prenatal screens can discover Down syndrome. Genetic counseling along with genetic testing, such as amniocentesis, chorionic villus sampling (CVS), or percutaneous umbilical blood sampling (PUBS) are usually offered to families who may have an increased chance of having a child with Down syndrome, or where normal prenatal exams indicate possible problems. Genetic screens are often performed on pregnant women older than 30 or 35.

Prenatal screening

Pregnant women can be screened for various complications in their pregnancy, or due to risk factors such as advanced maternal age. There are several common non-invasive screens that can indicate a Down syndrome fetus, and are normally performed in the late first trimester or early second trimester. Due to the nature of screens, each has a significant chance of suggesting a Down syndrome fetus when, in fact, the fetus does not have this genetic abnormality. Such results are called false positives. Screen positives must be verified before a Down syndrome diagnosis is made. Common screening procedures for Down syndrome are given in Table 1.

Even with the best non-invasive screens, the detection rate is 90%–95% and the rate of false positive of 2%–5%. False positives can be caused by undetected multiple fetuses (very rare with the ultrasound tests), incorrect date of pregnancy, or normal variation in the proteins.

Confirmation of screen positive is normally accomplished with amniocentesis. This is an invasive procedure and involves taking amniotic fluid from the mother and identifying fetal cells. The lab work can take a couple of weeks and will detect over 99.8% of all numerical chromosomal problems with a very low false positive rate.^[20] The vast majority of early screen positives are false. Since the risk of spontaneous abortion is approximately 1/200 to 1/300,^[21] amniocentesis confirmation presents a risk of spontaneously aborting a healthy fetus (from a false positive).

A 2002 literature review of elective abortion rates found that 91–93% of pregnancies with a diagnosis of Down syndrome were terminated.^[22] Physicians and ethicists are concerned about the ethical ramifications,^[23] with some commentators calling it "eugenics by abortion".^[24] Many members of the disability rights movement "believe that public support for prenatal diagnosis and abortion based on disability contravenes the movement's basic philosophy and goals."^[25]

Cognitive development

Cognitive development in children with Down syndrome is quite variable. Many can be successful in school, while others struggle. Because of this variability in expression of Down syndrome, it is important to evaluate children individually. The cognitive problems that are found among children with Down syndrome can also be found among children without Down syndrome. This means that parents can take advantage of general programs that are offered through the schools or other means. Children with Down syndrome have a wide range of abilities. It is not possible at birth to predict their capabilities. The identification of the best methods of teaching each particular child ideally begins soon after birth through early intervention programs.^[26]

Language skills show a difference between understanding speech and expressing speech. It is common for children with Down syndrome to need speech therapy to help with expressive language.^[27] Fine motor skills are delayed^[28] and often lag behind gross motor skills and can interfere with cognitive development. Occupational therapy can address these issues.^[29]

In education, mainstreaming of children with Down syndrome is controversial. Mainstreaming is when students of differing abilities are placed in classes with their chronological peers. Children with Down syndrome do not age emotionally/socially and intellectually at the same rates as children without Down syndrome, so eventually the intellectual and emotional gap between children with and without Down syndrome widens. Complex thinking as required in sciences but also in history, the arts, and other subjects is often beyond their abilities, or achieved much later than in most children. Therefore, if they are to benefit from mainstreaming without feeling inferior most of the time, special adjustments must be made to the curriculum.^[30]

Some European countries such as Germany and Denmark advise a two-teacher system, whereby the second teacher takes over a group of children with disabilities within the class. A popular alternative is cooperation between special education schools and mainstream schools. In cooperation, the core subjects are taught in separate classes, which neither slows down the typical students nor neglects the students with disabilities. Social activities, outings, and many sports and arts activities are performed together, as are all breaks and meals.^[31]

Health

The medical consequences of the extra genetic material in DS are highly variable and may affect the function of any organ system or bodily process. The health aspects of Down syndrome encompass anticipating and preventing effects of the condition, recognizing complications of the disorder, managing individual symptoms, and assisting the individual and his/her family in coping and thriving with any related disability or illnesses.^[32]

The most common manifestations of Down syndrome are the characteristic facial features, cognitive impairment, congenital heart disease, hearing deficits, short stature, and Alzheimer's disease. Other less common serious illnesses include leukemia, immune deficiencies, and epilepsy. Down syndrome can result from several different genetic mechanisms. This results in a wide variability in individual symptoms due to complex gene and environment interactions. Prior to birth, it is not possible to predict the symptoms that an individual with Down syndrome will develop. Some problems are present at birth, such as certain heart malformations. Others become apparent over time, such as epilepsy.

Genetic research

Down syndrome disorders are based on having too many copies of the genes located on chromosome 21. In general, this leads to an overexpression of the genes.^[33]^[34] Understanding the genes involved may help to target medical treatment to individuals with Down syndrome. It is estimated that chromosome 21 contains 200 to 250 genes.^[35] Recent research has identified a region of the chromosome that contains the main genes responsible for the pathogenesis of Down syndrome,^[36] located proximal to 21q22.3. The search for major genes involved in Down syndrome characteristics is normally in the region 21q21–21q22.3.

Recent use of transgenic mice to study specific genes in the Down syndrome critical region is has yielded some results. APP (Mendelian Inheritance in Man (OMIM) 104760, located at 21q21) is an Amyloid beta A4 precursor protein. It is suspected to have a major role in cognitive difficulties.^[37] Another gene, ETS2 (Mendelian Inheritance in Man (OMIM) 164740, located at 21q22.3) is Avian Erythroblastosis Virus E26 Oncogene Homolog 2. Researchers have "demonstrated that overexpression of ETS2 results in apoptosis. Transgenic mice overexpressing ETS2 developed a smaller thymus and lymphocyte abnormalities, similar to features observed in Down syndrome."^[38]

Sociological and cultural aspects

Advocates for people with Down syndrome point to various factors, such as special education and parental support groups, that make life easier for parents. There are also great strides being made in education, housing, and social settings to create "Down-friendly" environments. In most developed countries, since the early 20th century many people with Down syndrome were housed in institutions or colonies and excluded from society. However, in the 21st century there is a change among parents, educators and other professionals generally advocating a policy of "inclusion",^[39] bringing people with any form of mental or physical disability into general society as much as possible. In many countries, people with Down syndrome are educated in the normal school system and there are increasingly higher quality opportunities to mix "special" education with regular education settings.

Despite this change, reduced abilities of people with Down syndrome pose a challenge to their parents and families. While living with their parents is preferable to institutionalization for most people with Down syndrome, they often encounter patronising attitudes and discrimination in the wider community. In the past decade many couples with Down Syndrome have married and started homes of their own, overcoming many of the stereotypes associated with this condition.

The first World Down Syndrome Day was held on 21 March 2006. The day and month were chosen to correspond with 21 and trisomy respectively. It was proclaimed by Down Syndrome International.^[40]

History

English physician John Langdon Down first characterized Down syndrome as a distinct form of mental retardation in 1862, and in a more widely published report in 1866 entitled "Observations on an ethnic classification of idiots".^[41] Due to his perception that children with Down syndrome shared physical facial similarities (epicanthal folds) with those of Blumenbach's Mongolian race, Down used terms such as mongolism and mongolian idiocy.^[42] Idiocy was a medical term used at that time to refer to a severe degree of intellectual impairment. Down wrote that monoglism represented "retrogression," the appearance of Mongoloid traits in the children of allegedly more advanced Caucasian parents.

By the 20^th century, "mongolian idiocy" had become the most recognizable form of mental retardation. Most people with it were institutionalized. Few of the associated medical problems were treated, and most died in infancy or early adult life. With the rise of the eugenics movement, 33 of the 48 United States and a number of countries began programs of involuntary sterilization of individuals with Down syndrome and comparable degrees of disability. The ultimate expression of this type of public policy was the German euthanasia program "Aktion T-4" begun in 1940. Court challenges and public revulsion led to discontinuation or repeal of such programs during the decades after World War II.

Until the middle of the 20th century, the cause of Down syndrome remained unknown, although the presence in all races, the association with older maternal age, and the rarity of recurrence had been noticed. Standard medical texts assumed it was due to a combination of inheritable factors which had not been identified. Other theories focused on injuries sustained during birth.^[43]

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.^[44] The extra chromosome was subsequently labeled as the 21st, and the condition as trisomy 21.

In 1961, a group of nineteen geneticists wrote to the editor of The Lancet suggesting that mongolian idiocy had "misleading connotations," had become "an embarrassing term," and should be changed.^[45] The Lancet supported Down's Syndrome. The World Health Organization (WHO) officially dropped references to mongolism in 1965 after a request by the Mongolian delegate.^[46]

In 1975, the United States National Institute of Health convened a conference to standardize the nomenclature of malformations. They recommended eliminating the possessive form: "The possessive use of an eponym should be discontinued, since the author neither had nor owned the disorder."^[47] While both the possessive and non-possessive forms are used in the general population, Down syndrome is the accepted term among professionals in the USA, Canada and other countries, while Down's syndrome continues to be used in the United Kingdom and other areas.^[48]

Notable individuals

The Down Syndrome Association of Los Angeles has a more complete list of individuals with Down syndrome in roles in TV and movies.

Portrayal in fiction

References

^ Roizen NJ, Patterson D.Down's syndrome. Lancet. 2003 Apr 12;361(9365):1281-9. Review. PMID 12699967
^ Debra Wood (2005). Down syndrome. Retrieved on 2006-06-30.
^ Keep Kids Healthy article on Down syndrome.
^ Strom, C. FAQ from Mosaic Down Syndrome Society. Retrieved on 2006-06-03.
^ BBC News (22 September 2005). Down's syndrome recreated in mice. Retrieved on 2006-06-14.
^ For a description of human karyotype see Mittleman, A. (editor) (1995). An International System for Human Cytogenetic Nomeclature. Retrieved on 2006-06-04.
^ ^a ^b ^c Down syndrome occurrence rates (NIH). Retrieved on 2006-06-02.
^ Mosaic Down Syndrome on the Web
^ Leshin, L. (2000). Mosaic Down Syndrome. Retrieved on 2006-06-02.
^ Petersen MB, Tranebjaerg L, McCormick MK, Michelsen N, Mikkelsen M, Antonarakis SE. Clinical, cytogenetic, and molecular genetic characterization of two unrelated patients with different duplications of 21q. Am J Med Genet Suppl. 1990;7:104-9. PMID 2149934
^ Hook, E.B. (1981). "Rates of chromosomal abnormalities at different maternal ages". Obstet Gynecol 58: 282.
^ Based on estimates by National Institute of Child Health & Human Development Down syndrome rates. Retrieved on 2006-06-21.
^ Center for Disease Control (6 January 2006). "Improved National Prevalence Estimates for 18 Selected Major Birth Defects, United States, 1999-2001". Morbidity and Mortality Weekly Report 54 (51 & 52): 1301-1305.
^ Hook, E.B. (1981). "Rates of chromosomal abnormalities at different maternal ages". Obstet Gynecol 58: 282.
^ Estimate from National Down Syndrome Center. Retrieved on 2006-04-21.
^ Margareta Mikkelsen, Hanne Poulsen, Kim G. Nielsen (2006). "Incidence, survival, and mortality in Down syndrome in Denmark". American Journal of Medical Genetics 37 (S2): 75-78. Retrieved on 2006-07-03.
^ ^a ^b For a current estimate of rates, see Benn, PA, J Ying, T Beazoglou, JFX Egan. "Estimates for the sensitivity and false-positive rates for second trimester serum screening for Down syndrome and trisomy 18 with adjustments for cross-identification and double-positive results". Prenatal Diagnosis 21 (1): 46-51.
^ ^a ^b Some practices report adding Nasal Bone measurements and increasing the detection rate to 95% with a 2% False Positive Rate.
^ NIH FASTER study (NEJM 2005 (353):2001). See also J.L. Simplson's editorial (NEJM 2005 (353):19).
^ Fackler, A. Down syndrome. Retrieved on 2006-09-07.
^ Benke, P, V. Carver, R Donahue. Risk and Recurrence Risk of Down Syndrome. Retrieved on 2006-09-07.
^ Caroline Mansfield, Suellen Hopfer, Theresa M. Marteau (1999). "Termination rates after prenatal diagnosis of Down syndrome, spina bifida, anencephaly, and Turner and Klinefelter syndromes: a systematic literature review". Prenatal Diagnosis 19 (9): 808-812. This is similar to 90% results found by David W. Britt, Samantha T. Risinger, Virginia Miller, Mary K. Mans, Eric L. Krivchenia, Mark I. Evans (1999). "Determinants of parental decisions after the prenatal diagnosis of Down syndrome: Bringing in context". American Journal of Medical Genetics 93 (5): 410 - 416.
^ Glover, NM and Glover, SJ (1996). "Ethical and legal issues regarding selective abortion of fetuses with Down syndrome". Ment. Retard. 34 (4): 207-214. PMID 8828339.
^ George Will (14 April 2005). "Eugenics By Abortion: Is perfection an entitlement?". Washington Post: A37. Retrieved on 2006-07-03.
^ Erik Parens and Adrienne Asch (2003). "Disability rights critique of prenatal genetic testing: Reflections and recommendations". Mental Retardation and Developmental Disabilities Research Reviews 9 (1). Retrieved on 2006-07-03.
^ New Parent Guide. National Down Syndrome Society. Retrieved on 2006-05-12. Also Research projects - Early intervention and education. Retrieved on 2006-06-02.
^ Bird, G. and S. Thomas (2002). "Providing effective speech and language therapy for children with Down syndrome in mainstream settings: A case example". Down Syndrome News and Update 2 (1): 30-31. Also, Kumin, Libby (1998). “Comprehensive speech and language treatment for infants, toddlers, and children with Down syndrome”, Hassold, T.J.and D. Patterson Down Syndrome: A Promising Future, Together. New York: Wiley-Liss.
^ Development of Fine Motor Skills in Down Syndrome. Retrieved on 2006-07-03.
^ M. Bruni. Occupational Therapy and the Child with Down Syndrome. Retrieved on 2006-06-02.
^ S.E.Armstrong. Inclusion: Educating Students with Down Syndrome with Their Non-Disabled Peers. Retrieved on 2006-05-12. Also, see Debra L. Bosworth. Benefits to Students with Down Syndrome in the Inclusion Classroom: K-3. Retrieved on 2006-06-12. Finally, see a survey by NDSS on inclusion, Gloria Wolpert (1996). The Educational Challenges Inclusion Study. National Down Syndrome Society. Retrieved on 2006-06-28.
^ There are many such programs. One is described by Action Alliance for Children, K. Flores. Special needs, "mainstream" classroom. Retrieved on 2006-05-13. Also, see Flores, K.. Special needs, "mainstream" classroom. Retrieved on 2006-05-13.
^ American Academy of Pediatrics Committee on Genetics (Feb 2001). "American Academy of Pediatrics: Health supervision for children with Down syndrome". Pediatrics 107 (2): 442-449. PMID 11158488.
^ R Mao, CL Zielke, HR Zielke, J Pevsner (2003). "Global up-regulation of chromosome 21 gene expression in the developing Down syndrome brain". Genomics 81 (5): 457-467.
^ Rong Mao, X Wang, EL Spitznagel, LP Frelin, JC Ting, H Ding, J Kim, I Ruczinski, TJ Downey, J Pevsner (2005). "Primary and secondary transcriptional effects in the developing human Down syndrome brain and heart". Genome Biology 6 (13): R107.
^ See Leshin, L. (2003). Trisomy 21: The Story of Down Syndrome. Retrieved on 2006-05-21.
^ Zohra Rahmani, Jean-Louis Blouin, Nicole Créau-Goldberg, Paul C. Watkins, Jean-François Mattei, Marc Poissonnier, Marguerite Prieur, Zoubida Chettouh, Annie Nicole, Alain Aurias, Pierre-Marie Sinet, Jean-Maurice Delabar (2005). "Down syndrome critical region around D21S55 on proximal 21q22.3". American Journal of Medical Genetics 37 (S2): 98-103.
^ Chandra Shekhar (6 July 2006). Down syndrome traced to one gene. The Scientist. Retrieved on 2006-07-11.
^ OMIM, NIH. V-ETS Avian Erythroblastosis virus E26 Oncogene Homolog 2. Retrieved on 2006-06-29.
^ See the pamphlet: Inclusion: Educating Students with Down Syndrome with Their Non-Disabled Peers. National Down Syndrome Society. Retrieved on 2006-05-21.
^ World Down Syndrome Day. Retrieved on 2006-06-02.
^ Down, J.L.H. (1866). "Observations on an ethnic classification of idiots". Clinical Lecture Reports, London Hospital 3: 259-262. Retrieved on 2006-07-14. For a history of the disorder, see OC Ward (1998). John Langdon Down, 1828-1896. Royal Society of Medicine Press. ISBN 1853153745. or Conor, Ward. John Langdon Down and Down's syndrome (1828 - 1896). Retrieved on 2006-06-02.
^ (1999). "John Langdon Down: The Man and the Message". Down Syndrome Research and Practice 6 (1): 19-24. Retrieved on 2006-06-02.
^ Warkany, J. (1971). Congenital Malformations. Chicago: Year Book Medical Publishers, Inc, 313-314. ISBN 0-8151-9098-0.
^ Jérôme Lejeune Foundation. Retrieved on 2006-06-02.
^ Allen, Gordon, C.E. Benda, J.A. Böök, C.O. Carter, C.E. Ford, E.H.Y. Chu, E. Hanhart, George Jervis, W. Langdon-Down, J. Lejeune, H. Nishimura, J. Oster, L.S. Penrose, P.E. Polani, Edith L. Potter, Curt Stern, R. Turpin, J. Warkany, and Herman Yannet (1961). "Mongolism (Correspondence)". The Lancet 1 (7180): 775.
^ Howard-Jones, Norman (1979). "On the diagnostic term "Down's disease"". Medical History 23 (1): 102-104. PMID 153994.
^ A planning meeting was held on 20 March 1974, resulting in a letter to The Lancet. (1974). "Classification and nomenclature of malformation (Discussion)". The Lancet 303 (7861): 798. The conference was held 10-11 February 1975, and reported to The Lancet shortly afterward. (1975). "Classification and nomenclature of morphological defects (Discussion)". The Lancet 305 (7905): 513.
^ Leshin, Len (2003). What's in a name. Retrieved on 2006-05-12.

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