DOWN SYNDROME

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Down syndrome (DS), is the most common human aneuploidy that makes its appearance at birth and it' s the most common genetic cause of mental retardation. It was first identified as trisomy of chromosome 21 in 1959. Down syndrome is the most common autosomal abnormality and occurs in approximately 1 case per 700 live births.

In 1866, 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 made the first distinction between children who were cretins (later to be found to have hypothyroidism) and what he referred to as “Mongoloids” in an asylum for children with mental retardation in Surrey, England .Down gave this name to these children as he thought they 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 they stopped using it for a scientific reason. As a result, this condition was called “Down Syndrome”.

Down syndrome has been reported in people of all races and both sexes are being affected equally. However, symptoms can present some differences from males to females. Males with Down syndrome are sterile. In the few affected females who have had children, about one half of the offspring have been affected. In addition, there are symptoms that can appear in both sexes suffering from DS. These can be less severe, such as thyroid, hearing and eye problems, but also they can decrease the duration of life or affect its condition. Some of these symptoms are immune system problems, which make the patient very corruptible to viruses or pathogenic microorganisms, developmental delay, mental retardation, leukemia and other cancers and Alzheimer’s disease.

There has been a recent research on how increased absence of telomeres (ends of chromosomes consisting of highly conserved TTAGGG repeats) may indicate Alzheimer’s disease status in older individuals with DS and dementia. For this experiment, geneticians compared adults with DS and dementia to adults with DS but without dementia. For the conduction of the experiment, FITC labeled peptide nucleic acid probes have been used.The results not only show that the number of “visible” telomere signals is significantly less in people with DS and dementia versus those in age and sex matched controls with DS only, and they suggest that adults with DS without dementia can be distinguished from adults with DS experiencing cognitive decline, presumably associated with the progression of Alzheimer Disease, simply by counting the number of chromosome arms with no signal from the FITC-labeled PNA telomere probe. If these results are confirmed in a larger sample, findings will provide the foundation for a diagnostic procedure having both high sensitivity and specificity. As already mentioned, shorter telomeres have been found in people with AD compared to controls [18, 10] and in people with DS and dementia and people with DS only [14], and recently shorter telomeres have been observed in people with reduced immune function who are caregivers of patients with AD [6].

Except from the symptoms of DS, factors that make this desease appear can be worth mentioning. Nearly 95% of DS cases is due to a complete extra chromosome 21. About 90% of them is a result of a maternal meiotic error .The remaining 4% results from a Robertsonian (ROB) Translocation. Of those, 25% of ROB DS is familial whereas the remainder is de novo. Mosaic DS comprises 1–2% of cases.

There has been a research in Robertsonian translocation (ROB) so that there would be able to define the possible breakage area in 21p where ROB occurs. In the case of ROB, , 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."For the experiment, ten cases of ROB DS have been collected from three medical centers. Of the ten children, six had a de novo ROB translocation (60%), and four were inherited (40%).The phenotype of these ten cases were recorded and at least 90% of ROB DS had features of epicanthal folds, short stature, muscle hypotonia, and mental retardation. The incidence of congenital heart disease was 80%. One child had duodenal atresia but no child in the study had been diagnosed with an imperforate anus, Hirschsprung disease, or leukemia.

As Down Syndrome is one of the most common human aneuploidy, there have been researches on what could be done to prevent its appearance. A Down syndrome diagnosis can be made during prenatal testing. A diagnosis can also be made shortly after birth. In this case, the doctor may suspect that a baby has Down syndrome by the presence of possible characteristics of the condition. A Down syndrome diagnosis is confirmed with a special blood test. Prenatal testing includes Amniocentesis, Chorionic villus sampling (CVS) , Percutaneous umbilical blood sampling (PUBS).

In amniocentesis, a sample of the fluid surrounding the fetus is withdrawn. CVS is similar to amniocentesis, except that the procedure is done in the first trimester, and the fetal cells needed for examination are taken from the placenta. Neither procedure is used routinely, except when there is a family history of genetic defects, the pregnant woman is older than 35, or other medical indications are present. Percutaneous umbilical blood sampling is the most accurate method used to confirm the results of CVS or amniocentesis. In PUBS, the tissue is tested for the presence of extra material from chromosome 21. PUBS cannot be done until a woman is 18 to 22 weeks pregnant.

Articles:

Gene dosage change of TPTE and BAGE2 and breakpoint

analysis in Robertsonian Down syndrome

Sheng-Wen Shaw Ζ Chih-Ping Chen Ζ Po-Jen Cheng Ζ Tzu-Hao Wang Ζ

Jia-Woei Hou Ζ Cheng-Tao Lin Ζ Shuenn-Dhy Chang Ζ Hsiao-Lin Hwa Ζ

Ju-Li Lin Ζ An-Shine Chao Ζ Yung-Kuei Soong Ζ Fon-Jou Hsieh

Received: 19 October 2007 / Accepted: 13 November 2007 / Published online: 12 December 2007

_ The Japan Society of Human Genetics and Springer 2007

Increased “absence” of telomeres may indicate Alzheimer’s disease/dementia

status in older individuals with Down syndrome

Edmund C. Jenkinsa,∗, Lingling Yea, Hong Gua, Samantha A. Nia, Charlotte J. Duncana,Milen Velinova, Deborah Pangb,c, Sharon J. Krinsky-McHaleb,Warren B. Zigmanb,

Nicole Schupf b,c,d, Wayne P. Silvermane.

3 articles by : Assen L Dourmishev, MD, PhD, DSc, Professor of Dermatology, Consultant Dermatologist, Department of Dermatology, Medical Institute of the Ministry of Internal Affairs

Assen L Dourmishev is a member of the following medical societies:European Academy of Dermatology and Venereology and Sigma Xi
Coauthor(s): Camila K Janniger, MD, Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, New Jersey Medical School )