Down Syndrome

What Causes Down Syndrome?

The cells of people with Down syndrome have an extra copy (or an extra part of a copy) of a specific chromosome. A chromosome is a structure containing the genes that control how our cells develop and behave. A normal cell contains 23 pairs of chromosomes; one chromosome in each pair is inherited from the mother, and the other is passed along from the father. In Down syndrome, abnormal cell division before birth results in an extra copy of a particular chromosome (called chromosome 21). The additional genetic material causes cells to develop and behave abnormally.

Types of Down Syndrome

Three different types of Down syndrome are characterized by how abnormal chromosomal development happens in the cells.

• Trisomy 21. This type occurs when there is a separate extra copy of chromosome 21. This is the most common type of the disorder, affecting about 95% of people with Down syndrome.
• Translocation Down syndrome. This type happens when an extra copy or extra fragment of chromosome 21 is attached to a different chromosome rather than a distinct extra copy. This is a rare form, affecting only about 3% of people with Down syndrome.
• Mosaic Down syndrome. In this type, some of the person’s cells have an extra copy of chromosome 21, but other cells have the usual two copies. The effects of the disorder tend to be milder in this type. Mosaic Down syndrome is the rarest type, accounting for only about 2% of cases.

Is Down Syndrome Hereditary?

Down syndrome is a genetic disorder, but it is not usually passed on from parents to their children. The abnormal cell division that results in the syndrome typically occurs spontaneously, not because of any specific genetic trigger in the cells.

Translocation Down syndrome, however, may be passed from parent to child. In this case, the parent may possess some dislocated genetic material without having symptoms of the disorder themselves. When this dislocated material is passed on, it can cause Down syndrome in the child. However, not all translocation Down syndrome cases are inherited, and this type of the disorder is rare overall.

How is Down Syndrome Detected?

Down syndrome is often detected before birth. In cases where it is not diagnosed before birth, the syndrome’s distinctive physical features make it easy to diagnose at birth. It is unusual for the disorder to escape notice, even in its earliest stages.

Early intervention is essential, however. Prompt treatment of potentially life-threatening physical complications is vital, and preventive measures can help decrease the risk of further complications in the future. Dealing effectively with the disorder and its effects can help support children as they cope with its challenges early in life.

How is Down Syndrome Diagnosed?

Detection of Down syndrome during pregnancy can be approached in two different ways. Screening tests don’t directly detect Down syndrome, but they look for indications that the risk of Down syndrome is elevated. Diagnostic tests look directly for the genetic signs of Down syndrome. These tests are more definitive than screening tests, but they carry a risk to the mother and baby. Therefore, they may not be used unless the pregnancy is considered to be high-risk.

Screening Tests

• Blood tests. These tests examine the mother’s blood for levels of hormones and proteins that could suggest Down syndrome. These tests are routinely performed during all pregnancies.
• Ultrasound. An ultrasound imaging may reveal abnormalities in the baby’s neck that are characteristic of Down syndrome or other genetic disorders.

Diagnostic Tests

• Chorionic villus sampling (CVS). This test extracts cells from the placenta and examines them for indications of Down syndrome. This test is usually performed during the first trimester of the pregnancy, and it carries a low risk of causing a miscarriage.
• Amniocentesis. This test examines a sample of the fluid in the amniotic sac surrounding the baby. This test is usually performed in the second trimester, and it also carries a low risk of miscarriage.
• Percutaneous umbilical blood sampling (PUBS). This test examines blood from the umbilical cord for indications of Down syndrome. It is less commonly used but may be ordered when the results of other diagnostic tests are inconclusive. Like other diagnostic tests, it carries a small risk of miscarriage and other complications.

Post-Birth Genetic Testing

Although a visual examination is typically enough to detect Down syndrome, sometimes physical features resembling those of Down syndrome are present in babies without the disorder. Because of this, doctors will usually order a genetic blood test to confirm the diagnosis.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How is Down Syndrome Treated?

There is no cure for Down syndrome, and no treatment will reverse its effects. However, treatments for health complications can prevent them from becoming severe or life-threatening.

Depending on each individual’s specific challenges, various therapies can help a person with Down syndrome live a full, productive, happy life.

How Does Down Syndrome Progress?

Down syndrome uniquely affects each individual, and each person will face different complications and risks. The disorder has the potential to cause a wide array of physical and health problems. The challenges of the disorder’s developmental and cognitive effects can also put a person with Down syndrome at increased risk of additional physical and mental health complications.

Common complications of Down syndrome include:

• Heart defects
• Gastrointestinal defects
• Vision and hearing impairment
• Infections
• Leukemia
• Hypothyroidism
• Spinal malformation
• Celiac disease
• Motor development delays
• Epilepsy
• Sleep disorders
• Dental problems
• Depression and anxiety
• Attention-deficit/hyperactivity disorder
• Dementia and Alzheimer’s disease

How is Down Syndrome Prevented?

The cause of the abnormal cell division that leads to Down syndrome is unknown. This makes it difficult to find ways to prevent the disorder. However, some factors increase the risk of Down syndrome.

• Age of the mother. The eggs of women over the age of 35 are at a greater risk of abnormal division, so the risk of Down syndrome is more significant when a woman becomes pregnant after that age.
• Having a previous child with Down syndrome. The risk of having a child with Down syndrome is greater for parents who have already had a child with the disorder.
• Carrying genetic translocation. Parents who carry translocated genetic material from chromosome 21 have a greater risk of having a child with Down syndrome.

A genetic counselor can help you assess the risk if any of these risk factors apply to you.

Down Syndrome Caregiver Tips

As a caregiver for someone with Down syndrome, especially if that person is your child, you’re likely to worry about the future. With the proper support, your child can live a very full and successful life, and if you learn how to give and find that support, you can put worry aside.

• Teach your child to be independent. Give your child the opportunity to do things for themselves whenever possible. Be alert to your child’s unique strengths and challenges, and find ways to foster self-sufficiency in everyday tasks and situations.
• Don’t be isolated. Stay involved in social activities and events. Allow your child to be a part of the wider world, where they can learn and explore.
• Plan ahead. Think about the skills your child will need in adulthood, especially if you expect your child to live independently eventually. Begin building those skills as early as possible, and plan to develop a support system that will be there for your child in the years ahead.

Many people with Down syndrome also suffer from other brain-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with DDS:

• People with DS often experience mood disorders such as depression.
• Children with DS are at increased risk for epilepsy.
• People with DS sometimes also exhibit attention-deficit/hyperactivity disorder (ADHD).
• DS is sometimes co-morbid with autism.

Down Syndrome Brain Science

Down syndrome causes problems with learning and memory, so it has always been evident to scientists that the disorder’s chromosomal abnormalities affect the brain. Exactly how and why the chromosomal problems impact brain function, however, has not yet been discovered. As researchers attempt to better understand Down syndrome’s effect on the brain, the eventual goal is to use that knowledge to develop more effective therapies or treatments.

• Imaging studies have shown that people with Down syndrome have smaller brain volumes than people without the disorder. In particular, people with Down syndrome tend to have smaller frontal lobes and cerebellums, parts of the brain vital for language and memory processing. The hippocampus, which also plays a crucial role in learning and memory, also tends to be smaller.
• One study has suggested that the hippocampus might not function properly in patients with Down syndrome. The dysfunction could impair the patient’s ability to connect past experiences with current situations, a disability that could result in significant problems with learning and information processing.

Down Syndrome Research

Title: Developing a Down Syndrome Health Instrument

Stage: Recruiting

Principal investigator: Stephanie Santoro, MD, MGH

Massachusetts General Hospital

Boston, MA

Although over 200,000 individuals with DS live in the United States, studies to date have focused on outcomes apart from health. The foundation for this proposal is based on the need to accurately measure the health of all individuals – specifically, with DS – and the shortage of available tools for this population. Creating such an instrument will provide a barometer of the current state of health for DS and in future research. In this project, Dr. Santoro proposes to create an instrument that directly assesses health in DS – the Down syndrome Health Instrument (DHI). More specifically, the aims of this proposal are: 1. To conduct focus groups among caregivers, individuals with DS, panels of experts on DS and primary care physicians, and cognitive interviews to refine a conceptual model of health for DS and create an item pool, 2. To administer the DHI and establish internal validity, reliability, and external validity of the DHI for use in clinical research, and 3. To test the usability of the DHI in two pilot settings: research and clinical. This instrument will measure patient-reported health in DS for the first time and allow measurement of health as an outcome which is not currently possible in this population. This can identify gaps in care, then direct and optimize interventions that will improve care.

Title: Evaluating Cognitive Outcomes in Down Syndrome (ECODS-2)

Stage: Recruiting

Principal investigator: Anna Esbensen, PhD

Children’s Hospital Medical Center

Cincinnati, OH

As basic and behavioral science identify new ways to improve cognition and behavior in individuals with Down syndrome (DS), the lack of rigorous outcome measures represents an important problem for interpreting findings. Null findings in clinical trials could result from insensitive outcome measures, rather than the ineffectiveness of treatment.

The long-term goal is to improve the measurement of outcomes for children and adults with DS. Towards that goal, the investigators propose to test and refine a battery of cognitive measures that can be used in treatment studies focused on school-aged children and adults with Down syndrome. The batteries of tests are designed to assess key domains of the DS phenotype where gaps remain in outcome measures, including attention, executive function, learning and memory, processing speed, and social cognition.

The investigators will examine the psychometric properties of measures (test-retest, validity, sensitivity to change) and evaluate differences in the psychometric properties of measures as a function of variations in participant age, gender, degree of ID, and the participants’ physical health and medical comorbidities. The investigators will evaluate at least 80 children and 50 adults with Down syndrome, per site, at five time points to evaluate key domains with a diverse and novel range of methods. This proposal aims to provide a preliminary evaluation to support the enhancement of clinical outcome measures, which ultimately will increase the accuracy in documenting improvements in the lives of children and young adults with Down syndrome. 

 Title: Investigating the Experience of Living With Down Syndrome and Obstructive Sleep Apnea Syndrome (Stage 1)

Stage: Recruiting

Contact: Ignacio E. Tapia, MD

The Children’s Hospital of Philadelphia

Philadelphia, PA

This is a multi-center outpatient study to be performed at two clinical sites: Children’s Hospital of Philadelphia and Cincinnati Children’s Hospital. Forty Caregivers of children with DS and OSAS treated with PAP and their children will be enrolled. The study comprises one 30-minute open-ended semi-structured interview per caregiver. The duration of the interview is approximate. It will last up to 30 minutes as some families may want to include more details.