Trisomy 21, also called Down syndrome, is the most common chromosomal variation at birth,- affecting about 1 in every 700 liveborn babies. Down syndrome is usually caused by an extra copy of chromosome 21 with either the egg cell or sperm cell which created the pregnancy; ; this occurs during sex cell division through from an uncontrollable, random event called chromosomal nondisjunction.

Children born with trisomy 21 have 47 total chromosomes instead of the 46 which are usually observed in people without trisomy 21. The additional DNA housed within the extra chromosome 21 influences the physical, intellectual, and behavioral development of people with Down syndrome. Each and every person with Down syndrome will have slightly different features associated with the diagnosis, but some of the most common traits linked to Down syndrome include learning delays, recognizable facial features, and weak muscle tone in infancy.

Our understanding of trisomy 21 is constantly evolving, and today there are more resources for people with trisomy 21 than ever before. In 1910, children with Down syndrome were expected to survive to age 9. Recent advancements in clinical treatments, together with heightened advocacy for people with differing abilities have helped to increase the lifespan of individuals with Down syndrome. In fact, as many as 80% of adults with Down syndrome reach age 60, and many live even longer. With careful planning, engaged support systems, and comprehensive medical care, people with Down syndrome can lead long, happy, and fulfilling lives, even though they may encounter more daily challenges than people who do not have Down syndrome.

What are the physical features of Down syndrome? 

Every person is unique, and the physical features of trisomy 21 — both physical and intellectual — can vary widely. Common traits can include:

  • Flattened nasal bridge
  • Upward slanting eyes
  • Small ears
  • Short neck
  • Weak muscle tone
  • A single crease across the palms
  • Smaller hands and feet compared to peers
  • Shorter height compared to peers
  • Delayed cognitive development and learning difficulties
  • Delayed speech and language skills
  • Behavioral issues, such as problems concentrating, stubbornness, tantrums, and obsessive-compulsive behaviors

Trisomy 21 is also associated with a higher risk of other medical complications, including:

  • Congenital heart defects which may or may not require surgery in infancy or early childhood
  • Blood conditions, such as leukemia
  • Gastrointestinal problems, such as gastroesophageal reflux and celiac disease
  • Vision and hearing issues
  • Immune disorders
  • Hypothyroidism
  • Obesity
  • Sleep apnea

Our understanding of trisomy 21 is constantly evolving, and today there are more resources for helping those with the syndrome than ever before.

What causes trisomy 21?

When a baby is conceived, the inherited genetic material is derived from a sperm cell (usually with 23 chromosomes) and an egg cell (also usually with 23 chromosomes). Sometimes, however, an egg or a sperm cell will have more or fewer than the expected 23 chromosomes. If fertilization occurs, this can result in a pregnancy and potentially a liveborn baby with a different number of chromosomes than the 46 which are seen in most people.

In children with Down syndrome, either the sperm cell or the egg cell that created the baby had an extra 21st chromosome. As a result, the baby has three total copies of chromosome 21, which is why the medical term for Down syndrome is trisomy 21.

While there is no definitive scientific research that indicates that Down syndrome is caused by environmental factors or the parents’ activities before or during pregnancy, some parents have a greater chance of having a baby with Down syndrome, including:

  • Maternal age - People with egg cells are born with all the egg cells they will ever have. With increasing age, the chance for nondisjunction (unequal chromosome division) also increases. As such, women and people with egg cells who are 35 years old and older at delivery are considered to be at “high risk” to have a pregnancy with a chromosome variation, including Down syndrome. 
  • Having a previous child with Down syndrome - Compared to other people their same age category, people who have had one child with trisomy 21 have a slightly increased chance of having a second child with trisomy 21.
  • Having a chromosomal translocation in a genetic parent - Although uncommon, people who have a translocation involving chromosome #21 have an increased chance to have a baby with Down syndrome. This form of Down syndrome, called “translocation Down syndrome,” is only observed in ~2% of all people with Down syndrome, and can be diagnosed through a specific laboratory test called a karyotype. Parents of children with Down syndrome can also have their blood analyzed through a karyotype to examine whether they a chromosomal translocation involving the 21st chromosome. Genetic counseling services can help all types of prospective parents understand their family history and consider their genetic testing options to promote peace of mind. 

How is Down syndrome detected or diagnosed? 

First trimester - Non-invasive prenatal screening (NIPS) is available as early as 9 weeks gestation through a simple blood test. Genetic counselors are specially trained healthcare professionals who may be involved in interpreting results from NIPS, together with your obstetrical provider(s), to help inform parents of the chance for trisomy 21 in their pregnancy.  An ultrasound evaluation called a nuchal translucency sonogram can also look for physical features of Down syndrome in your fetus. Remember, since the fetus is still quite small at the time of the first trimester nuchal translucency sonogram (~11-13 weeks gestation), it’s difficult to distinguish as much of the baby’s anatomy compared to ultrasounds performed later in pregnancy. 

Second trimester: An anatomy ultrasound, usually performed around 18-20 weeks gestation, is a routine prenatal evaluation to examine the physical structures of the baby and placenta. It’s possible that this examination can identify “soft markers” for Down syndrome, such as a blockage in the bowel, a bright spot in the heart, or a shortened nasal bone. 

Other blood-based screening tests, such as the quadruple marker screen or “quad screen,” can help assess the likelihood of Down syndrome as well as a birth defect/birth difference alled spina bifida. The quad screen is typically performed between 15 and 21 weeks gestation, but has higher false positive rates and lower detection rates than NIPS.

If early screening tests show an elevated chance for fetal Down Syndrome, your doctor or other healthcare provider might recommend confirmatory diagnostic testing —  such as chorionic villus sampling (CVS) and amniocentesis. These diagnostic procedures can examine the chromosomes of the placenta and amniotic fluid, respectively, to confirm the number and structure of your baby’s chromosomes. 

Third trimester: While most people will have already received any Down syndrome screening results by the end of their second trimester, some people may choose to have NIPS in their third trimester if they learn new information about their baby’s growth and development on a later sonogram. If you’ve already had NIPS in your first or second trimester, you don’t need to repeat that blood test in the same pregnancy!

At birth: If prenatal evaluations such as NIPS or ultrasound were suggestive of Down syndrome, the doctor will perform a careful physical examination and order a blood test called a karyotype (chromosome analysis) to diagnose trisomy 21. Even if there was no suspicion for Down syndrome prenatally, if physical features of Down syndrome are noticed at birth, the baby’s care team can order diagnostic testing then. 

A preliminary diagnostic test called FISH (fluorescent in situ hybridization) analysis can offer results for chromosomes 21, 18, 13, X, and Y within ~48 hours, while the complete karyotype typically takes 10-14 days for final results.

What are the different types of Down syndrome? 

Down syndrome can be caused by one of three chromosomal mechanisms:

  • Trisomy 21 (~95% of cases) - As the embryo develops, the extra chromosome 21 is replicated in every cell of the body
  • Mosaicism (~2% of cases) - The extra chromosome 21 is present in some cells, but not all cells
  • Translocation (~3% of cases) - All or part of chromosome 21 is attached (translocated) to another chromosome, resulting in cells that have two standalone copies of chromosome 21 as well as another copy of chromosome 21 attached to another chromosome

It’s not usually possible to distinguish between trisomy 21 Down syndrome, mosaic trisomy 21, and translocation Down syndrome simply based on physical examination findings. It’s very important to determine the mechanism of Down syndrome through a karyotype analysis, since translocation Down syndrome can run in some families. While some people with mosaic Down syndrome may have very subtle features of the condition compared to people with full trisomy 21, it’s impossible to precisely predict how many symptoms, or the severity of symptoms, that a fetus or newborn baby will have.

What are the treatment options for T21?

Although there is currently no cure, children with Down syndrome benefit from comprehensive medical assistance and developmental interventions beginning during infancy. Special education and assistance in school is often very beneficial for children with Down syndrome, in addition to the resources from speech therapy, physical therapy, and occupational therapy. Children with Down syndrome are expected to meet developmental milestones such as rolling over, sitting up, crawling, walking, talking in complete sentences, and more – they just tend to meet these milestones at a slower pace than other children their age. As they get older, most people with Down syndrome will be able to go to school, make and maintain friendships, have and enjoy jobs, and be active members of their community. 

A new diagnosis of Down syndrome can evoke many different feelings for expectant or new parents.  Support groups for children and adults with Down syndrome, as well as for their siblings, parents, and other close family members, offer tremendous benefits to a family’s social and emotional wellbeing. While some families choose to connect with a Down syndrome support group very shortly following a new prenatal diagnosis, others may not join such a community until after their baby is born, or until they feel more ready. When working with a family navigating a new Down syndrome diagnosis, genetic counselors will offer ways to connect with local and national parent and family support groups, and emphasize that it’s completely up to the individual to determine when is the best time in their own journey to consider plugging into these support resources. 

We know it's a lot of information to digest, so we created an infographic:

Trisomy 21

JunoDx.com and the materials and information it contains are not intended to be and do not constitute medical advice, other health advice, or diagnosis.  Do not use JunoDx.com or the materials and information published at JunoDx.com as a substitute for medical care and treatment. You should always consult with a qualified physician or healthcare provider about your specific circumstances.

September 29, 2022 — Stephanie McClintock