Down syndrome (or Down's syndrome) is a chromosomal disorder caused by an error in cell

division that results in an extra 21st chromosome. The condition leads to impairments in both
cognitive ability and physical growth that range from mild to moderate developmental disabilities.
Through a series of screenings and tests, Down syndrome can be detected before and after a baby
is born.
The only factor known to affect the probability of having a baby with Down syndrome is maternal
age. That is, less than one in 1,000 pregnancies for mothers less than 30 years of age results in a
baby with Down syndrome. For mothers who are 44 years of age, about 1 in 35 pregnancies results
in a baby with Down syndrome. Because younger women generally have more children, about 75 80% of children with Down syndrome are born to younger women.

How is Down syndrome screened and diagnosed?

Some families have prenatal exams that indicate various possible problems, and others already
know that they have an increased chance of having a child with Down syndrome. These families
often receive screening and diagnostic tests for the condition. It is also standard for pregnant women
older than 30 or 35 to receive genetic screens because the risk of having a child with Down
syndrome is increased as women age.
Screening tests are used to estimate the risk that a fetus has Down syndrome, and diagnostic tests
can tell whether the fetus actually has the condition. Screening tests are a cost-effective and less
invasive way to determine if more invasive diagnostic tests are needed. However, unlike diagnostic
tests, screening tests cannot give definite answers as to whether the baby has Down syndrome.
Diagnostic tests, which are 99% accurate in detecting Down syndrome and other problems, are
usually performed inside the uterus and carry an extra risk of miscarriage, fetal injury, or preterm
labor.
Screening tests include:

Nuchal translucency testing (at 11 to 14 weeks) - an ultrasound that measures clear space
in folds of tissue behind the neck of a developing baby

Triple screen or quadruple screen (at 15 to 18 weeks) - measures the quantities of normal
substances in the mother's blood

Integrated screen - combines first trimester screening tests (with or without nuchal
translucency) and blood tests with second trimester quadruple screen

Genetic ultrasound (at 18 to 20 weeks) - Detailed ultrasound combined with blood test
results.

Diagnostic tests include:

Chorionic villus sampling (at 8 to 12 weeks) - analysis of a tiny sample of placenta obtained
from a needle inserted into the cervix or the abdomen

Amniocentesis (at 15 to 20 weeks) - analysis of a small amount of amniotic fluid obtained

from a needle inserted into the abdomen

Percutaneous umbilical blood sampling (after 20 weeks) - analysis of a small sample of

blood from the umbilical cord obtained from a needle inserted into the abdomen.

Down syndrome can also be diagnosed after a baby is born by inspecting the infant's physical
characteristics as well as blood and tissue samples that are stained to show chromosomes grouped
by size, number, and shape.

Silencing the extra chromosome may be possible

Scientists from the Massachusetts Medical School say they have made the first step
towards chromosome treatment for Down syndrome. They explained in the journal Nature (July
2013 issue) that a naturally occurring genetic technique to switch off the extra chromosome 21 was
achieved in test-tube cells.
Shutting off a single gene is a challenging task in itself, doing the same for a whole chromosome,
never mind a trisomic cell, was considered impossible.
Team leader, Jeanne Lawrence, said "..correction of hundreds of genes across an entire extra
chromosome has remained outside the realm of possibility. We now have a powerful tool for
identifying and studying the cellular pathologies and pathways impacted directly due to overexpression of chromosome 21."
The team is planning a new animal study to determine whether they can correct chromosome
defects in mouse models of Down syndrome.

KIDS
Health Problems Are Common
About half of babies with Down syndrome are born with heart defects, which means their hearts developed differently
and don't work as they should. Usually, these problems can be corrected by surgery. Some babies may have
intestinal problems that also require surgery to fix.
Kids with Down syndrome are more likely to get infections that affect their lungs and breathing. When they do get
infections, they often last longer. They may have eye or ear problems or digestion problems like constipation. Some
may develop leukemia, a type of cancer. Each person with Down syndrome is different and may have one, several, or
all of these problems.
Kids with Down syndrome tend to grow and develop more slowly than other children do. They may start walking or
talking later than other babies. Special help, such as physical therapy and speech therapy, can give kids a boost with
their walking and talking skills.

Times Have Changed

At one time, most kids with Down syndrome did not live past childhood. Many would often become
sick from infections. Others would die from their heart problems or other problems they had at birth.
Today, most of these health problems can be treated and most kids who have it will grow into
adulthood.
Medicines can help with infections and surgery can correct heart, intestinal, and other problems. If the
person gets leukemia, medical treatments can be very successful.
Down syndrome is something a person will have all of his or her life. But scientists continue to do
research in the hope of finding ways to prevent Down syndrome or at least improve the health and
lives of people who have it.

New Drugs May Transform Down Syndrome

Recent breakthroughs may lead to pharmacological treatments for the chromosomal disorder
Mar 1, 2014 |By Jenni Laidman

People born with Down syndrome have always been considered to be incurably
developmentally delayeduntil now. In the past few years a number of laboratories have

uncovered critical drug targets within disabled chemical pathways in the brain that might be
restored with medication. At least two clinical trials are currently studying the effects of such
treatments on people with Down syndrome. Now geneticist Roger Reeves of Johns Hopkins
University may have stumbled on another drug targetthis one with the potential to correct the
learning and memory deficits so central to the condition.
Down syndrome occurs in about one in 1,000 births annually worldwide. It arises from an extra
copy of chromosome 21 and the overexpression of each of the 300 to 500 genes the
chromosome carries. If you go back even as recently as 2004, researchers didn't have much of
a clue about the mechanisms involved in this developmental disability, says Michael Harpold,
chief scientific officer with the Down Syndrome Research and Treatment Foundation. But all that
has changed. In the past six or seven years there have been several breakthroughsand
breakthroughs is not by any means too big a wordin understanding the neurochemistry in
Down syndrome, Reeves says.
This improved knowledge base has led to a series of discoveries with therapeutic promise,
including the latest by Reeves. He and his team were attempting to restore the size of the
cerebellum in mice engineered to show the hallmarks of Down syndrome. The cerebellum lies at
the base of the brain and controls motor functions, motor learning and balance. In people with
Down syndrome and in the Down mouse model the cerebellum is about 40 percent smaller than
normal. By restoring its size, Reeves hoped to gain a clearer picture of the developmental
processes that lead to anomalies in a brain with Down syndrome.
Reeves's team injected newborn Down mice with a chemical that stimulates an important
neurodevelopmental pathway that, among other things, orchestrates cerebellum growth. We
were not in fact surprised that we fixed the cerebellum. That was our working hypothesis,
Reeves says. Yet he had not anticipated that three months after treatment the mice with a
restored cerebellum would be able to learn their way around a water mazea function of
learning and memory thought to be controlled by another part of the brain, the hippocampus.
The researchers do not yet know whether they inadvertently repaired the hippocampus or
whether the cerebellum might be responsible for more learning and memory functions than
previously realized.
In fact, other investigational treatments for Down syndrome target the hippocampusbut none
target this particular chemical pathway. Reeves's study, published recently inScience
Translational Medicine, may point to a pharmaceutical intervention that could allow those with
Down syndrome to live more independent lives. The possibility of actually giving Down

syndrome people the ability to improve learning and memory significantlythat's something I
never thought I'd see in my entire career, he says. And it's now happening. The game has
changed.

Characteristics of Down's syndrome

Down's syndrome can affect a person in many different ways and each individual
will experience different social and healthcare needs.

Physical appearance
People with Down's syndrome share a number of physical characteristics.
Not everyone will have all of them, but they may include:

reduced muscle tone which results in floppiness (hypotonia)

a small nose and flat nasal bridge

a small mouth

eyes that slant upwards and outwards

a big space between the first and second toe (sandal gap)

broad hands with short fingers

their palm may have only one crease across it (palmar crease)

a below average weight and length at birth

However, it is important to note that people with Down's syndrome do not all look the
same and will share physical features with their parents and family.

Delayed development
All children with Down's syndrome have some degree of learning disability and delayed
development, but this varies widely between individual children.
Babies with Down's syndrome also often have short arms and legs and low muscle tone,
making it harder for them to learn how to move.

Certain development milestones are often affected, including:

reaching
sitting
standing
walking
communicating
talking
reading
A small proportion of children with Down's syndrome have additional medical complications that
also affect their development (seecomplications of Down's syndrome).
Some children also experience autistic spectrum disorders (ASD) or attention deficit
hyperactivity disorder (ADHD).
These extra difficulties affect about 10% of children with Down's syndrome. Speak to the health
professionals working with your family for advice or an assessment if you believe your child may
be experiencing extra difficulties.
It is important to recognize that a child with Down's syndrome may still acquire many of the
cognitive and social skills most other people develop. It simply takes more time, and a child
should be allowed to move forward at their own pace.

Treating Down syndrome

Early intervention
Early intervention programmes are widespread for children with learning disabilities and help in all areas
of child development, as well as providing support to the family.
These programmes include speech and language therapy and physiotherapy, as well as individual home
teaching programmes for the child and family. Being part of an early intervention programme also gives
families the opportunity to find out about the syndrome, meet other families in similar situations and offer
support.

During the past 30 years, extensive research has taken place looking at how people with Down's
syndrome learn, and which skills are particularly challenging. There is now information for professionals
and families to use that enables children to develop the skills they need to get the most out of life.
Children and adults with Down's syndrome can and do continue to learn throughout their lives.
Your GP can give you further information about early intervention. You can also call the Down's Syndrome
Association helpline for more advice about early intervention (0333 121 2300). It is open Monday to
Friday between 10am and 4pm.

Adults with Down's syndrome

Further education and employment
Many young adults with Down's syndrome pursue further education. Some also gain employment, usually
on a part-time basis, although this will depend on the individual. Many people with Down's syndrome
enter loving relationships, although they may need guidance and support when it comes to things such
as contraception.

Living independently
With help and support, many adults with Down's syndrome are able to lead an active and independent
life. Although it may not be possible to live completely independently, increasing numbers of adults with
Down's syndrome are leaving home and living in their communities with support.
In most cases, adults with Down's syndrome move into property owned and staffed by a housing
association. The staff provide different levels of support, depending on the individual's particular needs.
Fertility
Men and women with Down's syndrome tend to have a reduced fertility rate. This does not mean they
cannot conceive children, but it does make it more difficult. Those who decide to have children will usually
need specialist guidance and support to help them cope with the physical and mental demands of a
newborn baby.
If a woman has Down's syndrome, the chance of her child also having the condition is 35-50%. It is
difficult to estimate the likelihood if both parents have the condition because this is still a very rare
occurrence. The risk of miscarriage and premature birth is greater in women with Down's syndrome.

latest research in down syndrome therapy

Research
Our research explores how children with Down syndrome develop and learn, and
identifies more effective teaching approaches and therapies. We have a unique focus
and a successful 30-year track record in delivering research that today is improving
educational outcomes for many thousands of young people with Down syndrome
around the world.

"The charity has had a profound impact on the Down syndrome research and practice community for the
past three decades. It combinesa scientifically grounded approach to educating individuals with
Down syndrome with a passion for improving the life of each child." (Professor Deborah Fidler,
Colorado State University, USA)

"The charity is now central to the worldwide understanding and sharing of research from many
academics and longer-term experience of those working with generations of children with Down
syndrome." (New Philanthropy Capital, London, UK)

Over the past 30 years, our studies have delivered important insights into speech and language, memory,
reading, number and mathematics, social skills, education, sleep and behaviour for children with Down
syndrome. Our research has repeatedly demonstrated the potential of children with Down syndrome to
learn more when given the opportunity and appropriate support.

Our unique focus

We focus on practical scientific studies of young people with Down syndrome that identify their precise
learning difficulties and that evaluate teaching approaches and therapies designed to meet their particular
needs.
We take a 'real world' view of development, studying learning for young people with Down syndrome in
everyday family life and in school. Many things influence development, including our genes, our families
and communities, and the opportunities that we are offered. Our research examines all of these factors in
the context of the complex and cumulative processes of human development.

Ensuring research makes a real difference

We ensure that our research delivers benefits for people with Down syndrome living today by identifying
and evaluating evidence-based interventions, and by disseminating our findings to families and
professionals worldwide.

A successful track record spanning 30 years

For over 30 years our work has delivered key advances in our understanding of the reading, language,
speech and memory difficulties experienced by children with Down syndrome, and pioneered techniques
that improve development and levels of educational achievement.
In the early 1980s, our research team was the first to identify that young children with Down syndrome
could learn to read and could learn to read surprisingly well at an early age. Since then, we have
sponsored and undertaken research in many areas of development for young people with Down
syndrome, including speech and language, memory, reading, number and mathematics, social skills,
education, sleep and behaviour.
Our research, resources and services have played a significant role in improving education for children
with Down syndrome. Only 30 year ago, it was widely thought that young people with Down syndrome
could not learn to read. Today, some 10%-20% of children with Down syndrome in mainstream primary
schools are reading as well as their typical classmates.

Recent achievements
We have recently completed two of the first randomised controlled trials of targeted interventions for
children with Down syndrome.

The first of these trials found that carefully structured daily reading and language teaching can improve
reading and language development for primary schoolchildren with Down syndrome. We are now
publishing a handbook and supplementary resources to support use of the intervention in schools
worldwide.
The second recent randomised controlled trial evaluated computer-based adaptive memory training
program with children with Down syndrome. The results of this study will be published shortly.
Other recent or ongoing research includes studies of early language development, the emergence of of
autism and autism-like behaviours in young children with Down syndrome, improving early problem
solving skills, teaching early phonics skills, early number teaching approaches, and attention skills.

researchers reveal how the alteration of a single nucleotide -- the basic building block of DNA -could initiate fragile X syndrome, the most common inherited form of intellectual disability. The
study appears inThe Journal of Cell Biology.

Fragile X syndrome is caused by a defect in a gene on the X chromosome called fragile X

mental retardation 1 (FMR1). Around 1 in 230 women and 1 in 360 men carry a so-called
premutation, in which a series of DNA repeats at one end of the FMR1 gene is slightly longer
than normal. These repeats are prone to even further expansion when FMR1 is passed from
mother to child, causing the gene to switch off and stop producing a protein that is important for
some cognitive functions.
A group of researchers from Albert Einstein College of Medicine of Yeshiva University in New
York previously found that a certain site that initiates DNA replication, located near to
the FMR1 gene, is inactivated in fragile X embryonic stem cells. This inactivation changes the
way that the FMR1 gene is copied during cell division, which could pose problems that lead to
expansion of the DNA repeats within the gene.
Intriguingly, a specific alteration in the DNA sequence near the FMR1 gene -- a "singlenucleotide polymorphism" or SNP -- has been linked to an increased risk of repeat expansion in
some premutation carriers. These researchers discovered that this SNP overlaps with the
inactive replication origin in fragile X embryonic stem cells.
Nucleotides in DNA include one of four bases (cytosine, thymine, adenine, or guanine). The
researchers found that normal embryonic stem cells had a thymine base at the SNP site and an
active replication origin. Fragile X cells, in contrast, had a cytosine base and an inactive origin.
The researchers also derived embryonic stem cells from mothers carrying the fragile X
premutation. These cells had a thymine base and a normal replication pattern and, accordingly,
showed no tendency to expand their repeat numbers over time.
The findings show that the substitution of cytosine for thymine might inactivate the DNA
replication origin when the FMR1 gene is passed from mother to child, increasing the risk of
DNA repeat expansions that can lead to fragile X syndrome.

XIST chromosome therapy

The UMMS team has reported initial success in silencing the additional chromosome in
pluripotent stem cellsdonated by a patient with Down syndrome. They achieved this by
inserting an RNA gene into the additional copy of chromosome 21.
This gene, called XIST, plays a role in turning off one of the two X chromosomes in
female mammals, and the UMMS researchers found that it was effective at repressing the
genes across the extra chromosome in their laboratory stem cells.

Now, Dr. Lawrence told MNT, the team is "working on inserting XIST into a trisomic chromosome of
two different mouse models, into embryonic stem cells."
"These are technically challenging experiments," she admitted, "and we have encountered some
issues with the embryonic stem cells available." Nevertheless, the team remains hopeful that their
XIST therapy can correct Down syndrome-related pathologies in a mouse model, "but it will be some
time before we have the full test of that in hand."
"When we first set out to test the feasibility of this in human Down syndrome patient-derived cells,
there was a large risk that the effort would take a long time and not be successful," she added. "So
one would have to be quite motivated to try this."
If Dr. Lawrence's XIST therapy is proved to be effective, she says that while it would provide
"probably not a full cure," the treatment may improve certain aspects of the condition in Down
syndrome patients, "but all need to be further developed and tested."
Dr. Lawrence is particularly interested in the associations between Down syndrome and Alzheimer's
and leukemia. "Down syndrome is important in itself," she said, "but it will be increasingly important
as a form of early-onset Alzheimer's disease, and study of this in Down syndrome will help the
broader population, which has a substantial chance to develop Alzheimer's disease with age."
"From my perspective, Dr. Lawrence's and colleagues' research is a very elegant study and a
spectacular accomplishment," Dr. Michael M. Harpold, chief scientific officer of the LuMind
Foundation, told MNT, adding: hough not involved in the UMMS study, the LuMind Foundation fund
research into a wide spectrum of Down syndrome-related research - from sleep and cognition to
restoring neuronal pathways.

New drug targets for improving cognitive function in people with

Down syndrome
Dr. Harpold identifies one area of research that is yielding particularly exciting results at the moment.
By identifying mechanisms involved in the developmental intellectual disability of Down syndrome as well as the early-onset Alzheimer's component of the condition - LuMind-associated research has
found specific drug targets that Dr. Harpold says "have been shown in the laboratory to mediate
improvement in cognitive function and/or ameliorate the Alzheimer's disease
associated neurodegeneration in Down syndrome."

This research includes the development of a novel anti-amyloid vaccine to prevent

Alzheimer's disease in people with Down syndrome, which is due to begin a clinical trial
soon.
In 2011, LuMind also partnered with the pharmaceutical company Roche in bringing a new drug
designed to address the cognitive and behavioral deficits of Down syndrome to clinical trial. A large,
multi-national phase 2 trial was initiated earlier this year, and Dr. Harpold describes the foundation
as being "extremely pleased" with the progress of the "landmark" trials so far.

IQ, sleep apnea and adaptive behavior

"There are significant new studies by Dr. Jamie Edgin and colleagues," Dr. Harpold says, "which
represent an important deeper understanding of the correlation between levels of cognitive function
and sleep dysfunction, including sleep apnea, in people with Down syndrome."
In her 2014 study published in the journal Developmental Medicine and Child Neurology, Dr. Edgin
and colleagues presented results demonstrating that children with Down syndrome who also have
sleep apnea average a verbal IQ score nine points lower than those without sleep apnea.
Her previous work - some of which we touched on in yesterday's spotlight feature - has looked at
the role "adaptive behavior" plays in "the Down syndrome advantage," where even though people
with Down syndrome have lower IQ scores than the general population, this does not necessarily
impede their overall well-being.
"IQ and adaptive behavior are two ways of measuring a person's functional level, with IQ having a
heavy focus on verbal learning," Dr. Edgin explained to MNT. "Adaptive behavior is a broad
functional measure that incorporates a wider set of daily living skills, including social skills, personal
living skills and communication."

Dr. Edgin is one researcher who believes that, as important as scientific breakthroughs are,
increasing understanding of people with Down syndrome among the general population is equally
essential.
"Through education and increased advocacy efforts we can help the community at large
understand individuals with Down syndrome and their strengths and weaknesses," she told
us.
"They are people first," she emphasized, "and as with all people they have areas in which they excel,
are happy and successful, and areas in which they need more support. Those who work with or love

people with Down syndrome must help educate others to overcome some common misperceptions
about Down syndrome."