Prenatal testing during pregnancy can detect chromosome abnormalities that may cause birth defects or intellectual disabilities in a baby. The most common chromosome abnormalities found through prenatal screening and diagnostic testing include Down syndrome, trisomy 18, trisomy 13, and sex chromosome abnormalities.
What is a chromosome abnormality?
Chromosomes are structures within each cell that contain genetic information. Humans typically have 23 pairs of chromosomes, with one chromosome from each pair inherited from the mother and one from the father. A chromosome abnormality occurs when there are missing, extra, or irregular parts of chromosomes.
Some examples of chromosome abnormalities include:
- Down syndrome – An extra copy of chromosome 21
- Trisomy 18 – An extra copy of chromosome 18
- Trisomy 13 – An extra copy of chromosome 13
- Turner syndrome – Only one X chromosome in females instead of the normal two
Chromosome abnormalities can alter development and cause congenital disabilities. Testing for chromosome abnormalities during pregnancy can help identify if a fetus is at increased risk for certain genetic conditions.
What prenatal tests screen for chromosome abnormalities?
There are two main types of prenatal testing options to screen for chromosome abnormalities during pregnancy:
- Screening tests – Assess risk through blood tests and ultrasound but do not diagnose chromosome abnormalities
- Diagnostic tests – Directly test fetal cells to confirm if a chromosome abnormality is present
Screening tests include:
- First trimester screening – Combines blood tests and ultrasound between weeks 11-13
- Quad screen – Blood test between weeks 15-20
- Cell-free DNA – Blood test that analyzes fetal DNA, typically done after week 10
Diagnostic tests include:
- Chorionic villus sampling (CVS) – Takes a sample of the placenta between weeks 10-13
- Amniocentesis – Samples amniotic fluid between weeks 15-20
Diagnostic tests are over 99% accurate at detecting chromosome abnormalities but do have a small risk of miscarriage. Screening tests have no risk to the pregnancy but only calculate the odds a fetus has a chromosome disorder.
Down Syndrome
Down syndrome is the most common chromosome abnormality, occurring in about 1 in 700 babies born in the United States each year. It is caused by an extra copy of chromosome 21 (trisomy 21).
Common features of Down syndrome may include:
- Distinctive facial features such as an upward slant to the eyes
- Low muscle tone and loose joints
- A single deep crease across the center of the palm
- Intellectual disability ranging from mild to severe impairment
- Increased risk of certain medical problems like heart defects, intestinal malformations, hearing and vision problems, thyroid dysfunction, and childhood leukemia
The risk of having a baby with Down syndrome increases with maternal age. Screening and diagnostic testing during pregnancy can detect over 95% of Down syndrome cases.
Down Syndrome Screening
There are several screening options available for Down syndrome:
- First trimester screening – detects about 80% of Down syndrome cases
- Cell-free DNA – detects over 99% of Down syndrome cases
- Quad screen – detects about 80% of Down syndrome cases
A positive screening result does not diagnose Down syndrome but indicates a higher risk. Diagnostic testing such as CVS or amniocentesis is recommended to confirm Down syndrome.
Down Syndrome Diagnostic Testing
| Test | How It’s Done | When It’s Done |
|---|---|---|
| Chorionic villus sampling (CVS) | A sample of the placenta is taken through the cervix or abdomen | 10-13 weeks |
| Amniocentesis | A sample of amniotic fluid is taken with a needle through the abdomen | 15-20 weeks |
CVS and amniocentesis allow chromosomal analysis of fetal cells. The detection rate for Down syndrome is over 99% with diagnostic testing.
Trisomy 18
Trisomy 18, also called Edwards syndrome, occurs in about 1 in 5000 births. It is caused by an extra copy of chromosome 18. Only 50% of babies with trisomy 18 live beyond the first week of life.
Common symptoms of trisomy 18 include:
- Severe intellectual disability
- Slow growth before birth
- Distinct facial features such as a small head, low-set ears, and clenched fists with overlapping fingers
- Birth defects involving the heart, kidneys, skeletal system, and gastrointestinal system
Due to the very high risk of infant mortality with trisomy 18, prenatal screening and diagnostic testing can help parents make informed decisions about pregnancy management and medical care planning.
Trisomy 18 Screening
First trimester screening and cell-free DNA testing can screen for trisomy 18 with a detection rate over 95%. Quad screen can identify about 80% of trisomy 18 pregnancies.
Trisomy 18 Diagnostic Testing
Chorionic villus sampling and amniocentesis diagnose over 99% of trisomy 18 cases by allowing chromosomal analysis of fetal cells. These diagnostic tests are recommended to confirm a positive trisomy 18 screening result.
Trisomy 13
Trisomy 13, or Patau syndrome, is caused by an extra copy of chromosome 13. It occurs in about 1 in 10,000 live births. Sadly, many babies with trisomy 13 are stillborn or pass away within their first weeks or months of life.
Common symptoms associated with trisomy 13 include:
- Severe intellectual disability
- Heart defects
- Brain malformations such as holoprosencephaly
- Facial abnormalities like a sloped forehead, low-set ears, and extra skin on the neck
- Abnormalities of hands and feet such as polydactyly
Due to the poor survival rates, prenatal diagnosis allows families time to plan for palliative care after birth and make informed decisions about managing the pregnancy.
Trisomy 13 Screening
Screening tests like the first trimester screen, quad screen, and cell-free DNA can detect about 80-95% of trisomy 13 cases.
Trisomy 13 Diagnostic Testing
As with trisomy 18, chorionic villus sampling and amniocentesis can diagnose over 99% of trisomy 13 pregnancies by analyzing the fetal chromosomes. Diagnostic testing should follow positive screening results.
Sex Chromosome Abnormalities
The sex chromosomes are the X and Y chromosomes that determine gender. Sex chromosome abnormalities occur when there are missing or extra sex chromosomes beyond the typical XX (female) and XY (male) pairs.
Examples of sex chromosome abnormalities include:
- Turner syndrome – Only one X chromosome in females (45,X)
- Klinefelter syndrome – XXY in males
- Triple X syndrome – XXX in females
- Jacob’s syndrome – XY in males
These conditions can cause problems with sexual development, fertility, learning, and physical features, but are usually less severe than autosomal trisomies involving chromosomes 13, 18 and 21. Cell-free DNA testing is the best noninvasive prenatal screening option for sex chromosome abnormalities.
Turner Syndrome
Turner syndrome affects about 1 in 2000 to 1 in 5000 females. Common features include:
- Short stature
- Lack of sexual development and infertility
- Lymphedema
- Heart defects
- Kidney problems
- Hearing loss
Cell-free DNA screening can detect over 90% of Turner syndrome pregnancies. Ultrasound can sometimes identify fluid collection behind the neck (nuchal cystic hygroma) as an early sign of Turner syndrome.
Klinefelter Syndrome
Klinefelter syndrome is present in about 1 in 500 to 1 in 1000 males. It often goes undiagnosed until puberty when signs become apparent:
- Small testes
- Lack of facial and body hair
- Enlarged breasts
- Tall stature
- Low testosterone
- Learning disabilities
Prenatal diagnosis of Klinefelter syndrome is possible with cell-free DNA screening, but many cases are still missed until adolescence.
Triple X Syndrome
Triple X syndrome occurs in around 1 in 1000 female births. Many girls have mild symptoms or none at all. When present, symptoms may include:
- Tall stature
- Delayed motor skills
- Speech and language difficulties
- Learning disabilities
Cell-free DNA screening and amniocentesis can identify Triple X syndrome prenatally. However, the mild nature of this syndrome means many cases are first detected in childhood.
Jacob’s Syndrome
Jacob’s syndrome, or XYY syndrome, affects 1 in 1000 male births. Many males with XYY have normal development but may have:
- Learning disabilities
- Delayed speech and motor skills
- Behavioral problems
- Tall stature
As with Klinefelter and Triple X syndromes, Jacob’s syndrome can be detected through cell-free DNA but mild cases often go unnoticed until childhood learning and behavioral challenges arise.
Conclusion
Screening and diagnostic tests for chromosome abnormalities are an important part of prenatal care. They allow early detection of genetic conditions caused by extra, missing, or irregular chromosomes. The most common chromosome abnormalities found prenatally include Down syndrome, trisomy 18, trisomy 13, and sex chromosome abnormalities such as Turner syndrome.
Knowing about a chromosome abnormality during pregnancy allows families time to prepare for special medical needs after birth. It also gives parents information to make decisions about pregnancy management and delivery planning. While screening tests calculate the odds of a disorder, diagnostic tests like CVS and amniocentesis can provide definitive diagnosis to guide care.
