Down Syndrome Overview

• There are 23 pairs of chromosomes, for a total of 46.
• Half the chromosomes come from the egg, and the other half from the sperm.
• This XY chromosome pair includes the X chromosome from the egg and the Y chromosome from the sperm.
• In Down syndrome, there is an additional copy of chromosome 21, resulting in three copies instead of the normal two copies.
• Trisomy 21 (also known by the karyotype 47,XX,+21 for females, 47,XY,+21 for males) is caused by a failure of the 21st chromosome to separate during egg and sperm development (nondisjunction).

Three Genetic Variations

Trisomy 21

About 95 percent of the time, Down syndrome is caused by trisomy 21 — the person has three copies of chromosome 21, instead of the usual two copies, in all cells. This is caused by abnormal cell division during the development of the sperm cell or the egg cell.

Mosaic Down syndrome

In this rare form of Down syndrome, a person has only some cells with an extra copy of chromosome 21. This mosaic of normal and abnormal cells is caused by abnormal cell division after fertilization.

Translocation Down syndrome

Down syndrome can also occur when a portion of chromosome 21 becomes attached (translocated) onto another chromosome, before or at conception. These children have the usual two copies of chromosome 21, but they also have additional genetic material from chromosome 21 attached to another chromosome.

Which of these variations are the cause for Brian’s Down Syndrome?

Risk Factor

Advancing maternal age

A woman’s chances of giving birth to a child with Down syndrome increase with age because older eggs have a greater risk of improper chromosome division. A woman’s risk of conceiving a child with Down syndrome increases after 35 years of age. However, most children with Down syndrome are born to women under age 35 because younger women have far more babies.

Being carriers of the genetic translocation for Down syndrome

Both men and women can pass the genetic translocation for Down syndrome on to their children.

Having had one child with Down syndrome

Parents who have one child with Down syndrome and parents who have a translocation themselves are at an increased risk of having another child with Down syndrome. A genetic counselor can help parents assess the risk of having a second child with Down syndrome.

Screening During Pregnancy

First trimester combined two step test

• Blood test-measures levels of pregnancy-associated plasma protein-A (PAPP-A) and human chorionic gonadotropin (HCG).  Abnormal levels of both may indicate a problem with the baby.
• Nuchal translucency test-an ultrasound is used to measure a specific area on the back of the fetus’s neck.  When abnormalities are present, more fluid tends to collect in this neck tissue.

Second trimester

• Blood test-measures four pregnancy-associated substances:  alpha fetoprotein, estriol, HCG, and inhibin A.
• If screening test results are positive or you are at high risk, more testing to confirm the diagnosis may be done.
• Chorionic villus sampling (CVS)-cells are taken from the placenta and analyzed. Usually done in the 1st trimester.  The risk of miscarriage is very low.
• Amniocentesis-sample of amniotic fluid is withdrawn using a needle inserted into the uterus to analyze the fetus chromosomes.  Done in 2nd trimester, risk of miscarriage is very low.

Additional Screening

Non-Invasive Prenatal Screening (NIPT)

• Optional blood test available from ~9 weeks gestation till end of pregnancy (more accurate than standard tests)
• Detects Trisomy 13, 18, and 21
• May be covered by OHIP if certain criteria are met (at least one of the following):
  • Maternal age 40+
  • Positive screening result/abnormal NT or ultrasound
  • Twin pregnancy
  • History of previous trisomy

Common Features of Down Syndrome

• Flattened face
• Small head
• Short neck
• Protruding tongue
• Upward slanting eye lids (palpebral fissures)
• Unusually shaped or small ears
• Poor muscle tone
• Broad, short hands with a single crease in the palm
• Relatively short fingers and small hands and feet
• Excessive flexibility
• Tiny white spots on the colored part (iris) of the eye called Brushfield’s spots
• Short height

Other Common Features

• May be of average size, but typically grow slowly and remain shorter than other children their age
• Most children with Down Syndrome have mild to moderate cognitive impairment
• Language is delayed
• Short- and long-term memory is affected

Complications

• Heart defects: About half the children with Down syndrome are born with some type of congenital heart defect. These heart problems can be life-threatening and may require surgery in early infancy.
• Gastrointestinal (GI) defects: GI abnormalities occur in some children with Down syndrome and may include abnormalities of the intestines, esophagus, trachea and anus. The risk of developing digestive problems, such as GI blockage, heartburn (gastroesophageal reflux) or celiac disease, may be increased.
• Immune disorders: Because of abnormalities in their immune systems, people with Down syndrome are at increased risk of developing autoimmune disorders, some forms of cancer, and infectious diseases, such as pneumonia.
• Sleep apnea: Because of soft tissue and skeletal changes that lead to the obstruction of their airways, children and adults with Down syndrome are at greater risk of obstructive sleep apnea.
• Obesity: People with Down syndrome have a greater tendency to be obese compared with the general population.
• Spinal problems: Some people with Down syndrome may have a misalignment of the top two vertebrae in the neck (atlantoaxial instability). This condition puts them at risk of serious injury to the spinal cord from overextension of the neck.
• Leukemia: Young children with Down syndrome have an increased risk of leukemia.
• Dementia: People with Down syndrome have a greatly increased risk of dementia — signs and symptoms may begin around age 50. Having Down syndrome also increases the risk of developing Alzheimer’s disease.
• Other problems: Down syndrome may also be associated with other health conditions, including endocrine problems, dental problems, seizures, ear infections, and hearing and vision problems.

Coping & Support

Parents may experience a range of emotions, including anger, fear, confused, scared, worry, and sorrow

The best antidote for fear and worry is information and support:

• Ask your health care provider about early intervention programs
• Learn about educational options for school
• Seek out other families who are dealing with the same issues
• Participate in social and leisure activities
• Encourage independence
• Prepare for the transition to adulthood
• Most people with Down syndrome live full lives.  Go to mainstream schools, participate in the community and have jobs.