Down syndrome strides

A third copy of chromosome 21 in each cell causes Down Syndrome. IMAGE COURTESY OF UPO649 1112 MREYCOR1, A WIKIMEDIA COMMONS USER

Named after John Langdon Down, an English physician who first described the disorder in 1866, Down syndrome is the most common cause of birth defects in the U.S. Every year, 6,000 babies are born with the congenital disorder, and the Centers for Disease Control and Prevention reports that cases of Down syndrome have increased by 24 percent in recent years. Although there is no standard treatment, children with Down syndrome can develop basic physical, cognitive, language and social skills with specialized education and care. During October’s National Down Syndrome month, the National Down Syndrome Society advocates the importance of early intervention and celebrates the unique strengths and talents of those with the syndrome.

What causes Down syndrome?

Down syndrome occurs when chromosome 21 fails to separate equally between two daughter cells during the formation of an egg or sperm. The error is called nondisjunction. If the abnormal cell contributes to a fertilized egg, the resulting embryo will have three copies of chromosome 21 in every cell. For this reason, the syndrome is also known as trisomy 21. The extra chromosome disrupts transcriptional regulation in cells via widespread changes in chromatin structure and methylation patterns.

What are the traits of the syndrome?

Common physical traits include low muscle tone, short stature and an upward slant to the eyes. Down syndrome also causes heart defects, cognitive impairment, language delays and poor memory.

What are the latest research developments?

Jeanne Lawrence and colleagues at the University of Massachusetts Medical School are exploring chromosomal therapy for treating Down syndrome. The team inserted a gene called X-inactive specific transcript, or XIST, into stem cells derived from trisomy 21 patients. XIST condenses and inactivates one of the two X chromosomes during mammalian female development. When inserted into the cells, XIST silenced most of the genes in the extra chromosome 21. The silencing also improved the stem cells’ ability to differentiate into neurons. Chromosomal silencing could improve cognitive function by restoring neuronal cells.

Other researchers are investigating the biochemical mechanisms behind cognitive defects observed in people with Down syndrome. Huaxi Xu and colleagues at the Sanford–Burnham Medical Research Institute found that a protein called sorting nexin 27, or SNX27, is abnormally low in people with Down syndrome. SNX27 helps neurons retain glutamate receptors, which is essential for synaptic signaling and brain function. Xu’s team showed that those with Down syndrome have low levels of SNX27 because the extra chromosome overproduces microRNA-155, a key inhibitor of SNX27.

In 2013, the National Institutes of Health launched a national registry for Down syndrome called DS-Connect. This centralized website enables easy exchange of information between patients, doctors and scientists. In 2015, the NIH introduced a Web portal within DS-Connect that allows approved scientists to access anonymized data about patients’ health. The portal will help scientists to coordinate clinical studies with eligible participants, perform customized searches and generate new research ideas based on the collective information available in the portal.

Indumathi Sridharan Indumathi Sridharan earned her bachelor’s degree in bioinformatics in India. She holds a Ph.D. in molecular biochemistry from Illinois Institute of Technology, Chicago. She did her postdoctoral work in bionanotechnology at Northwestern University.