June 23, 2008
Alternative namesTrisomy 21, Down Syndrome
DefinitionDown syndrome is a chromosome abnormality, usually due to an extra copy of the 21st chromosome. This syndrome usually, although not always, results in mental retardation and other conditions.
Causes, incidence, and risk factors
In most cases, Down syndrome is caused by an extra chromosome 21. It is the most common single cause of human birth defects, with an occurence in 1 out of every 660 births.
Down syndrome have a widely recognized characteristic
appearance. The head may be smaller than normal (microcephaly) and
shaped. Prominent facial features include a flattened nose, protruding
and upward slanting eyes. The inner corner of the eyes may have a
of skin (epicanthal fold) rather than coming to a point. The hands are
broad with short fingers and often have a single crease in the palm
crease). Retardation of normal growth and development is typical and
affected children never reach average adult height.
Congenital heart defects are frequently present in Down syndrome children. Early mortality is often a result of cardiac abnormalities. Gastrointestinal abnormalities such as esophageal atresia (obstruction of the esophagus) and duodenal atresia (obstruction of the duodenum) are also relatively common. Obstruction of the gastrointestinal tract may require major surgery shortly after birth. Children with Down syndrome also have a higher than average incidence of acute lymphocytic leukemia (ALL).
Signs and tests
A heart murmur may be revealed by listening to the chest with a stethoscope. Characteristic abnormalities are revealed by a physical examination. These include a flattened facial profile, small ears, separation of the abdominal muscles, joint hyperflexibility, awkward gait, extra skin on back of neck at birth, and an abnormal bone in the middle of the 5th finger.
Early and massive vomiting may indicate obstruction of the esophagus or duodenum and less often lower segments of the gastrointestinal tract. This is sometimes discovered by inability at birth to pass a tube from the nose into the stomach or duodenum as well as by special x-rays.
TreatmentThere is no specific treatment for Down syndrome. Special education and training is offered in most communities for mentally handicapped children. Specific heart defects may require surgical correction. The potential for visual problems, hearing loss, and increased susceptibility to infection will require screening and treatment at appropriate intervals.
Support GroupsNational Down Syndrome Congress
Expectations (prognosis)The normal life span is shortened in Down syndrome by congenital heart disease and by increased incidence of acute leukemia. Mental retardation is variable although usually of moderate severity. Some adults live independently and are accomplished individuals.
There is a risk that uninformed people may assume a Down syndrome child is more retarded than he or she is.
Calling your health care provider
A geneticist should be consulted to help determine the diagnosis and interpret rare chromosomal translocation cases of Down syndrome.
The health care provider should be consulted to evaluate the child for the need for special education and training. The need for follow-up of physical problems varies.
Genetic counseling is recommended in all families with Down syndrome. Down syndrome can be detected in a fetus in the first few months of pregnancy by examination of the chromosomes obtained by amniocentesis or chorionic villus sampling. The parents of a child with Down syndrome are at increased risk for having another child with Down syndrome. Mothers who become pregnant after age 40 are also at increased risk for having a child with Down syndrome.Update Date: 8/19/2003
Updated by: Douglas R. Stewart, M.D., Division of Medical Genetics, Hospital of the University of Pennsylvania, Philadelphia, PA. Review provided by VeriMed Healthcare Network.
Directory of Down Syndrome Sites
National Down Syndrome Society
Down Syndrome: Health Issues
The formal story began in 1866, when a physician named John Langdon Down published an essay in England in which he described a set of children with common features who were distinct from other children with mental retardation. Down was superintendent of an asylum for children with mental retardation in Surrey, England when he made the first distinction between children who were cretins (later to be found to have hypothyroidism) and what he referred to as "Mongoloids."
Down based this unfortunate name on his notion that these children looked like people from Mongolia, who were thought then to have an arrested development. This ethnic insult came under fire in the early 1960s from Asian genetic researchers, and the term was dropped from scientific use. Instead, the condition became called "Down's syndrome." In the 1970s, an American revision of scientific terms changed it simply to "Down syndrome," while it still is called "Down's" in the UK and some places in Europe.
In the first part of the twentieth century, there was much speculation of the cause of Down syndrome. The first people to speculate that it might be due to chromosomal abnormalities were Waardenburg and Bleyer in the 1930s. But it wasn't until 1959 that Jerome Lejeune and Patricia Jacobs, working independently, first determined the cause to be trisomy (triplication) of the 21st chromosome. Cases of Down syndrome due to translocation and mosaicism (see definitions of these below) were described over the next three years.
Chromosomes are thread-like structures composed of DNA and other proteins. They are present in every cell of the body and carry the genetic information needed for that cell to develop. Genes, which are units of information, are "encoded" in the DNA. Human cells normally have 46 chromosomes which can be arranged in 23 pairs. Of these 23, 22 are alike in males and females; these are called the "autosomes." The 23rd pair are the sex chromosomes ('X' and 'Y'). Each member of a pair of chromosomes carries the same information, in that the same genes are in the same spots on the chromosome. However, variations of that gene ("alleles") may be present. (Example: the genetic information for eye color is a "gene;" the variations for blue, green, etc. are the "alleles.")
Human cells divide in two ways. The first is ordinary cell division ("mitosis"), by which the body grows. In this method, one cell becomes two cells which have the exact same number and type of chromosomes as the parent cell. The second method of cell division occurs in the ovaries and testicles ("meiosis") and consists of one cell splitting into two, with the resulting cells having half the number of chromosomes of the parent cell. So, normal eggs and sperm cells only have 23 chromosomes instead of 46.
Many errors can occur during cell division. In meiosis, the pairs of chromosomes are supposed to split up and go to different spots in the dividing cell; this event is called "disjunction." However, occasionally one pair doesn't divide, and the whole pair goes to one spot. This means that in the resulting cells, one will have 24 chromosomes and the other will have 22 chromosomes. This accident is called "nondisjunction." If a sperm or egg with an abnormal number of chromosomes merges with a normal mate, the resulting fertilized egg will have an abnormal number of chromosomes. In Down syndrome, 95% of all cases are caused by this event: one cell has two 21st chromosomes instead of one, so the resulting fertilized egg has three 21st chromosomes. Hence the scientific name, trisomy 21. Recent research has shown that in these cases, approximately 90% of the abnormal cells are the eggs. The cause of the nondisjunction error isn't known, but there is definitely connection with maternal age. Research is currently aimed at trying to determine the cause and timing of the nondisjunction event.
the karyotype of a
male with trisomy 21:
Three to four percent of all cases of trisomy 21 are due to Robertsonian Translocation. In this case, two breaks occur in separate chromosomes, usually the 14th and 21st chromosomes. There is rearrangement of the genetic material so that some of the 14th chromosome is replaced by extra 21st chromosome. So while the number of chromosomes remain normal, there is a triplication of the 21st chromosome material. Some of these children may only have triplication of part of the 21st chromosome instead of the whole chromosome, which is called a partial trisomy 21. Translocations resulting in trisomy 21 may be inherited, so it's important to check the chromosomes of the parents in these cases to see if either may be a "carrier."
The remainder of cases of trisomy 21 are due to mosaicism. These people have a mixture of cell lines, some of which have a normal set of chromosomes and others which have trisomy 21. In cellular mosaicism, the mixture is seen in different cells of the same type. In tissue mosaicism, one set of cells, such as all blood cells, may have normal chromosomes, and another type, such as all skin cells, may have trisomy 21.
The chromosomes are holders of the genes, those bits of DNA that direct the production of a wide array of materials the body needs. This direction by the gene is called the gene's "expression." In trisomy 21, the presence of an extra set of genes leads to overexpression of the involved genes, leading to increased production of certain products. For most genes, their overexpression has little effect due to the body's regulating mechanisms of genes and their products. But the genes that cause Down syndrome appear to be exceptions.
Which genes are involved? That's been the question researchers have asked ever since the third 21st chromosome was found. From years of research, one popular theory stated that only a small portion of the 21st chromosome actually needed to be triplicated to get the effects seen in Down syndrome; this was called the Down Syndrome Critical Region. However, this region is not one small isolated spot, but most likely several areas that are not necessarily side by side. The 21st chromosome may actually hold 200 to 250 genes (being the smallest chromosome in the body in terms of total number of genes); but it's estimated that only a small percentage of those may eventually be involved in producing the features of Down syndrome. Right now, the question of which genes do what is highly speculative. However, there are some suspects.
Genes that may have input into Down syndrome include:
Other genes that are also suspects include APP, GLUR5, S100B, TAM, PFKL, and a few others. Again, it is important to note that no gene has yet been fully linked to any feature associated with Down syndrome.
Other genes that are also suspects include APP, GLUR5, S100B, TAM, PFKL, and a few others. Again, it is important to note that no gene has yet been fully linked to any feature associated with Down syndrome.
One of the more notable aspects of Down syndrome is the wide variety of features and characteristics of people with trisomy 21: There is a wide range of mental retardation and developmental delay noted among children with Down syndrome. Some babies are born with heart defects and others aren't. Some children have associated illnesses such as epilepsy, hypothyroidism or celiac disease, and others don't. The first possible reason is the difference in the genes that are triplicated. As I mentioned above, genes can come in different alternate forms, called "alleles." The effect of overexpression of genes may depend on which allele is present in the person with trisomy 21. The second reason that might be involved is called "penetrance." If one allele causes a condition to be present in some people but not others, that is called "variable penetrance," and that appears to be what happens with trisomy 21: the alleles don't do the same thing to every person who has it. Both reasons may be why there is such variation in children and adults with Down syndrome.
Researchers are busy in their attempts to map out the full structure of the chromosome, including the Human Genome Database. Because of the small size of the 21st chromosome and its association with Down syndrome, it is the second-most heavily mapped human chromosome. Research is focusing on trying to identify genes and their effects when overexpressed.
However, it would be a mistake to assume that the clinical features of Down syndrome are only due to a handful of genes being overexpressed. You can think of the overexpressed gene products interacting with a number of normal gene products, each product individualized by the person's unique genetic makeup, and thus being thrown "out of genetic balance." This would then make the person more susceptible to other genetic and environmental insults, leading to the features, diseases and conditions associated with Down syndrome. It is this complex arrangement that scientists will be addressing in the second century of Down syndrome research.
Aim High! (Albany, NY)
Bringing Up Down Syndrome (Southern NJ)
Bucks County DS Interest Group (PA)
Connecticut Down Syndrome Congress
Down Syndrome Group of Western PA
Down Syndrome Parent Network of Eastern PA
Down Syndrome Parent Support Group of Genesee County (NY)
Down Syndrome Society of Rhode Island
Down Syndrome Assoc. of Delaware
Hudson Valley Down Syndrome Assoc. (NY)
Assoc. of Fredericksburg, VA
Down Syndrome Assoc. of Hampton Roads (SE Virginia)
Down Syndrome Association of the Lowcountry Charleston, SC
Down Syndrome Assoc. of Memphis and Mid-South
Down Syndrome Assoc.of Middle Tennessee
Down Syndrome Assoc. of New Orleans
Down Syndrome Assoc. of Northern Virginia
DS Family and Friends (Little Rock, AR)
Down Syndrome of Louisville, KY
Gold Coast DS Org. of Broward County, FL
Gold Coast Org. of Palm Beach County, FL
Piedmont DS Support Network (N Carolina)
PODS Angels Support Group in Fort Lauderdale, FL
Triangle Down Syndrome Network (N Carolina)
Up With Downs (Shreveport, LA)
PC Downies (Panama City, FL)
Assoc. of Roanoke, Virgina
Down Syndrome Assoc. of Central Ohio
Down Syndrome Assoc. of Central Oklahoma
Down Syndrome Assoc. of Greater Cincinnati
Down Syndrome Assoc. of Greater St. Louis
Down Syndrome Association of Minnesota
Down Syndrome Assoc. of Northern Indiana
Down Syndrome Assoc. of West Michigan
Down Syndrome Assoc. of Wisconsin
Down Syndrome Development Counsel (N. Ill.)
F.E.D.S. (Sterling Heights, Mich)
Indiana DS Foundation (Indianapolis)
Kansas City Down Syndrome Guild Assoc.
Miami Valley Down Syndrome Assoc. (Dayton, OH)
National Assoc. for Down Syndrome (Chicago)
NDSS Nebraska (Omaha)
Oshkosh Down Syndrome Parent Support Group
Riverbend Down Syndrome Parent Support Group (SW Illinois)
SW Chicago Suburban Support Group
The Up Side of Downs of Greater Cleveland
Up With Down (Des Moines)
Wichita Downs Support Group
West & Southwest:
Down Syndrome Assoc. of Houston
Down Syndrome Assoc. of Los Angeles
Down Syndrome Association of Orange County (Cal.)
Down Syndrome Connection of Tucson
Down Syndrome Exchange, Southern Cal.
Down Syndrome Guild of Dallas
Down Syndrome Group of Salt Lake City
Down Syndrome League of the Greater Bay Area
DS Network (Phoenix, AZ)
Down Syndrome Organization of Southern Nevada
Down Syndrome Partnership of Tarrant County (Ft. Worth)
Down Syndrome Support Group of the High Desert
Down Syndrome Assoc of Ventura County (Cal.)
Sharing Down Syndrome Arizona
Southern Arizona Network for DS
Colorado Springs Down Syndrome Assoc.
Down Syndrome Outreach of Whatcom County (Wash.)
Mile High Down Syndrome Assoc. (Denver area)
Utah Down Syndrome Foundation
Hawaii Down Syndrome Congress
Alaska Chapter of the NDSC
Asociacion Down de Avellaneda
Asociación Síndrome de Down de la República Argentina
DS Society of South Australia
DS Assoc. of New South Wales
DS Assoc. of Victoria
DS Assoc. of Western Australia
Australian Capital Territory DS Assoc.
DS Assoc. of Queensland
Austria: Infoplattform Down-Syndrom Österreich
Bahrain: Bahrain Down Syndrome Society
Brazil: Fundacao Sindrome de Down
Calgary DS Assoc.
Canadian Down Syndrome Society
DS Assoc. of Metropolitan Toronto
Down Syndrome Research Foundation and Resource Centre
Manitoba DS Society Home Page
Newfoundland and Labrador DS Society
Assoc. du Syndrome de Down de L'estrie (Quebec)
Czech Republic: Spolecnost Downova syndromu
Forældre til mongolbørn i København
Landsforening Downs Syndrom
Ecuador: Frutos-Integral Attention Center
Egypt: European Down Syndrome Assoc. (EDSA)
Finland: Downin oireyhtymä
France: F.A.I.T 21 et G.E.I.S.T 21
Down syndrome network Germany
Deutschen Down-Syndrom InfoCenter
Honduras: Down Syndrome Foundation
Hong Kong: Down Syndrome Association
Iceland: Félag áhugafólks um Downs-heilkenni
India: Down's Syndrome Federation of India
Down Syndrome Ireland - Main branch
Down Syndrome Ireland - Mayo Branch
L'Associazione Italiana Persone Down
Associazione Genitori Bambini Down
Centro Bresciano Down
Pordenone DS Assoc. (English)
CE.N.TR.O. 21 -- Bologna
Sindrome di Down
Japan: Japan Down Syndrome Network (English version)
Luxembourg: Trisomie 21 Lëtzebuerg a.s.b.l. (in French and German)
Malta: Down Syndrome Assoc. of Malta
Maylasia: Kiwanis Down Syndrome Centre under construction
Resources in Mexico
Instituto Irapuatense Down, A.C.
Netherlands: Stichting Down's Syndroom
New Zealand: New Zealand DS Assoc.
Nigeria: Down Syndrome Association of Nigeria
Phillipines:Down Syndrome Assoc. of the Philippines
Puerto Rico: Fundación Síndrome Down
Down Syndrome Assoc. of Russia
Downside Up (this is a UK charity for Russian children with DS)
Singapore: Singapore Down Syndrome Assoc.
Slovakia: Spolocnost' Downovho syndrómu na Slovensku
South Africa: Down Syndrome South Africa
Down 21: Fundación Síndrome de Down
Fundación Asindown (Valencia)
Asociacion Sindrome de Down "Lejeune"
Fundacio Catalana Sindrome de Down
La Fundación Síndrome de Down de Cantabria
Downs Syndrom Sverige
Downs Syndrom - inte bara en extra kromosom
Insieme - Vereinigung für Kinder mit Down-Syndrom
Association Romande Trisomie 21
Turkey: Down sendromu Dayanisma Grubu
UK Resources for Down Syndrome
UK Down's Syndrome Assoc.
UK Mosaic Down Syndrome Assoc.
DS Assoc of Bristol
Greater Manchester Branch of the DS Assoc.
Down Syndrome Liverpool
North East & Cumbria Branch
Down's Syndrome Assoc. London Branch
Oxfordshire Group of the DS Assoc.
Scottish Down's Syndrome Assoc.
Kingston Special Needs Project
Inter Care Residential
Uruguay: La Asociacion Down del Uruguay
Other International, non-internet resources indexed at:
Descriptions of DS
A description of Down Syndrome characteristics by Dr. Siegfried M. Pueschel
Online Mendelian Inheritance in Man (OMIM) Page on DS (a medical description)
General Health Guidelines
Health Care Guidelines for People with DS
Spanish Edition of DSMIG Guidelines
Down Syndrome: Health Issues, from Dr. Len Leshin
Genetics of DS
Dr. Korenberg's Chromosome 21 Phenotype Mapping Project
Online Mendelian Inheritance in Man (OMIM) Gene Map of chromosome 21
Risk and Recurrence of Down Syndrome by Dr. Paul Benke
What is Mosaic Down Syndrome? by Carol Strom
Animations of Meiosis and Fertilization
Specific Medical Topics in DS
Alzheimer's in DS by Dr. Ira Lott
Brain and Tissue Bank for Developmental Disorders
Center for Motor Behavior in Down Syndrome
Dental Care in Down Syndrome: A Review of the Literature by Sindoor Desai, DDS
Down Syndrome & Autistic-Spectrum Disorder
Down's Syndrome Vision Research Group (Cardiff Univ., UK)
Down's Heart Group
Growth Charts for Children with Down Syndrome
Hip Instability in Down Syndrome by Kim Voss
Menstrual Management in Down Syndrome
My Brother and Me: about Down Syndrome and Alzheimer's
Child with Down Syndrome,
Breastfeeding and Down Syndrome, by the La Leche organization
Communicating Partners, Dr. James McDonald's program
Diagnosis: Down Syndrome (a collection of stories for new parents of children with DS)
Down Syndrome - For New Parents (by The Paul Family)
Down Syndrome for Family and Friends
Love and Learn Tapes for Teaching Reading
National Down Syndrome Education and Research Institute
Parents' Resource - For new parents (by the Edwards Family)
Welcome to Holland, by Emily P. Kingsley
Welcoming New Babies, by Pam Wilson
MetLife's "Division of Estate Planning for Special Kids"
Creative Exchange Music Therapy
OT Exchange: a site for pediatric Occupational Therapists and parents who utilize OTs
The Possible Dream
Down Syndrome Research Online Advocacy Group
The Lindsey Rae Foundation
Trisomy 21 Foundation of Northern New York
Personal Ponies for Children with Disabilities
Annie Forts' Up Syndrome Fund, Inc.
The Karen Gaffney Foundation
Foundation 21 (Australia)
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