Blood test for Down Syndrome

During pregnancy, the developing embryo sheds cells which are absorbed by the maternal blood stream. In most cases the cells are destroyed and cell-free fetal DNA remains. This fetal DNA is present in the mother's blood for many hours. And during pregnancy, there is a constant supply of this fetal DNA. Detecting genetic mutations and abnormalities has become an exciting prospect in diagnosis because of the less invasive detection - only requiring a blood sample from the mother. A recent paper was published comparing the accuracy of this method. Sensitivity and specificity were both 100% for trisomy 21. This diagnosis was made using DNA sequence reading by Verinata. But the company Sequenom is also capable of doing this. More companies are sure to emerge. The mean gestational age at the time of testing was 15 weeks. In future, tests such as these will ease the physical stress of diagnosis compared to current methods and also allow more time for pregnancy and family planning, and arrangement of medical support. Importantly, such testing will help those rural areas lacking obstetric expertise.
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Autism in Down syndrome

Criteria of autism spectrum disorders (ASD) are often applied to individuals with Down syndrome even though the validity of the criteria in this population is unclear. About 5% of individuals with Down syndrome exhibit repetitive stereotypic movements, but do they also have social communication deficits? There is also a greater incidence of intellectual disability in Down syndrome, that may cloud or confuse diagnosis of social communication skills. A recent report from the Kennedy Kreiger details the co-mobities. The importance of making these distinctions means that more appropriate interventions can be trialled. The other interesting observation comes from a consideration of the genetics. In Down syndrome, over 350 genes are present in excess on chromosome 21, compared to one gene in deficit in ASD, for example. This results in a reduced brain size in Down syndrome, but potentially increased brain size in ASD. What is particularly interesting is that 40% of individuals with Down syndrome have ASD (either PDD or autism). Therefore, despite (nearly all) individuals with Down syndrome having a defined and consistent genetic imbalance, not all of them develop ASD, motor stereotypies or display disruptive behaviour. The question now for researchers is Why? The challenge raised by the authors of the above study for educators is to develop a range of targetted interventions. 

Review of biology and treatments

A very comprehensive review of the state of current DS research has been published here

Decreased cell number in the cerebellum

It has been known for some time that there is a decreased number of cells in parts of the brain of individuals with DS. A recent study has confirmed this decrease in embryos. In the brain region responsible for involuntary movements and fine motor coordination - the cerebellum - researchers in Italy have show that there is a reduction in the number of new cells born. There was no change in the number of cells dying (which is also a natural developmental process in some situations). The decrease in cells in the cerebellum is thought to contribute to the decrease in motor coordination seen in some individuals with DS.
Find the article here
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Inhibition signalling in the brain

Recent studies have suggested that the major functional defect in a mouse model of DS may be an imbalance between excitation and inhibition brain signalling. This kind of imbalance is often seen to result in epilepsy. In a study by US researchers, the role of two DS genes was investigated. Here they found that by restoring the level of expression of these two genes to normal in the DS mouse, they could then restore the signalling imbalance. However, restoring the level of gene expression occurred from egg fertilisation and occurred throughout embryonic development, meaning that human gene therapy in young or adult individuals with DS may not produce an effect as great. Also, despite there being obvious brain changes in individuals with DS, there is substantial lack of evidence that the same brain signalling imbalance is occurring, as seen in the mouse model.
Additional commentary by the journal was made here
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Reduced cell proliferation

One of the changes in the brain of individuals with DS is a decreased brain size. Evidence exists that this is may due to a reduction in the production of new cells during early development. One of the genes in three copies present in DS is Dyrk1a. Over the last 10 years evidence has been mounting suggesting that Dyrk1a is responsible for many cell functions including cell proliferation. This was recently tested and confirmed in cell lines, a mouse expressing too much of Dyrk1a and human embryonic stem cells. The Dyrk1a gene therefore presents a possible target for therapeutic intervention of decreased brain size in individuals with DS. Having enough brain cells present may then assist the brain to arrange itself properly and contribute to better brain function.
Find the article here
Find a review of Dyrk1a function here

Anti-depressants as therapies for DS

Researchers in Italy have used an anti-depressant to restore the behaviour deficits of a mouse with DS. Researchers also found that drug treatment prevented loss of neurons. Until now, no study has explored the possibility of pharmacologically improving cell maturation defects in DS during critical periods of brain development. The anti-depressant used was fluoxetine - or Prozac. Fluoxetine blocks the reuptake of a chemical neurotransmitter 5HT into cells, by forcing the 5HT to remain outside the cell, it is more likely to activate neighbouring cells and improve communication between them. DS is not typically associated with depression. However, fluoxetine can act by other mechanisms in different situations. In DS, where brain stem cells are lacking, fluoxetine can increase the production of these. The other exciting aspect of this discovery is that fluoxetine is already approved by drug administration agencies around the world for use in humans. While it's use in infants is not wide spread, clinical testing here is sure to advance.

Read the article here.

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