Reasons Why Your Healthcare Provider May Order a Karyotype

Understanding Karyotypes

A karyotype is a visual representation of a person's chromosomes. It's literally a photograph of the chromosomes within a cell, arranged in pairs according to size and shape. Healthcare providers order karyotypes for various reasons. During pregnancy, a karyotype helps screen for common congenital defects (birth defects). It's also used to help confirm a diagnosis of leukemia. Less frequently, karyotypes are used in preconception screening for couples at increased risk of passing a genetic disorder to their child. The procedure for obtaining the sample varies depending on the reason for testing and may involve a simple blood test (phlebotomy), a bone marrow aspiration, amniocentesis (a procedure to collect amniotic fluid from the pregnant uterus), or chorionic villus sampling (CVS; a procedure to collect cells from the placenta).

Genetics Basics

Chromosomes are thread-like structures located within the nucleus of each cell. These structures carry our genetic information in the form of genes. We inherit half of our chromosomes from each parent, resulting in a total of 46 chromosomes: 22 pairs of autosomes (non-sex chromosomes) and one pair of sex chromosomes (XX for females and XY for males). Genes, the functional units of heredity, direct the synthesis of proteins. These proteins determine our physical traits, bodily functions, and overall health. Errors in the genetic code, whether involving the number or structure of chromosomes, can have significant effects on development and health, potentially increasing the risk of disease or physical/intellectual disability. Chromosomal abnormalities arise during cell division. Meiosis refers to cell division in the reproductive organs, while mitosis occurs in all other cells.

What a Karyotype Can Show

A karyotype analysis characterizes chromosomes based on their size, shape, and number. This allows for the identification of both numerical and structural abnormalities.

Numerical abnormalities involve an incorrect number of chromosomes. This can be a trisomy (an extra chromosome) or a monosomy (a missing chromosome). Some examples of numerical abnormalities detectable by karyotype:

Down syndrome (trisomy 21): An extra copy of chromosome 21 resulting in characteristic facial features, intellectual disability, and other health concerns.
Edward syndrome (trisomy 18): An extra copy of chromosome 18, often leading to severe health problems and typically resulting in death before the first birthday.
Patau syndrome (trisomy 13): An extra copy of chromosome 13, associated with severe intellectual disability, heart defects, and a high mortality rate in the first year.
Turner syndrome (monosomy X): A missing or damaged X chromosome in females, leading to short stature, infertility, and heart defects.
Klinefelter syndrome (XXY syndrome): An extra X chromosome in males, causing reduced fertility, learning disabilities, and underdeveloped genitalia.

Structural abnormalities involve changes in the structure of one or more chromosomes. These may include:

Deletions: A portion of a chromosome is missing.
Translocations: A segment of one chromosome breaks off and attaches to a different chromosome.
Inversions: A segment of a chromosome breaks off, flips around, and reattaches.
Duplications: A segment of a chromosome is duplicated.

Examples of conditions resulting from structural abnormalities:

Charcot-Marie-Tooth disease: Duplication of chromosome 17, leading to muscle weakness and loss of sensation in the extremities.
Cri-du-Chat syndrome: Deletion of part of chromosome 5, causing distinctive cat-like cries in infants and intellectual disability.
Philadelphia chromosome: A translocation between chromosomes 9 and 22, strongly associated with chronic myeloid leukemia (CML).
Williams syndrome: Deletion of a segment of chromosome 7, resulting in distinctive facial features, cardiovascular problems, and developmental delays.

Importantly, not all chromosomal abnormalities result in disease. Some may even have beneficial effects. For example, carrying one copy of the sickle cell gene provides protection against malaria.

Indications for Karyotype Testing

A karyotype may be ordered for several reasons:

Prenatal diagnosis: To detect chromosomal abnormalities in a fetus during pregnancy.
Preconception screening: For couples with a family history of chromosomal disorders, a known genetic disorder in one parent, or a shared ancestral history increasing the risk of a recessive disorder. This is particularly relevant for couples from ethnic groups with higher frequencies of specific genetic conditions (e.g., Ashkenazi Jewish couples and Tay-Sachs disease, or African American couples and sickle cell disease).
Recurrent miscarriage: Karyotyping may be done for couples who have experienced multiple miscarriages to identify potential genetic causes.
Infertility: Parental karyotyping may be helpful in evaluating infertility cases if other causes have been ruled out.
Suspected leukemia: A karyotype may aid in confirming a diagnosis of leukemia, particularly chronic myeloid leukemia (CML), by detecting the presence of the Philadelphia chromosome. Note that the Philadelphia chromosome alone isn't definitive proof of leukemia.

How Karyotypes are Performed

Karyotyping can be performed using almost any cell type. However, in clinical practice, samples are most commonly obtained via:

Amniocentesis: A needle is inserted into the pregnant uterus to collect amniotic fluid, usually between weeks 15 and 20 of pregnancy. This procedure carries a small risk of miscarriage.
Chorionic villus sampling (CVS): A needle is used to obtain a sample of placental tissue, typically between weeks 10 and 13 of pregnancy. CVS carries a slightly higher risk of miscarriage than amniocentesis.
Phlebotomy (blood draw): A blood sample is obtained from a vein. White blood cells are then isolated for analysis.
Bone marrow aspiration: A needle is used to collect a sample of bone marrow, often used for leukemia diagnosis.

Sample Evaluation: A cytogeneticist, a specialist in chromosome analysis, evaluates the collected sample. Cells are grown in a lab to encourage cell division. Then, the chromosomes are stained, photographed under a microscope, and arranged in pairs to create the karyotype. The karyotype is then analyzed to identify any numerical or structural abnormalities.

Results

A karyotype report details any chromosomal abnormalities found, specifying the chromosome involved and the type of abnormality. The interpretation of the findings may be described as "possible," "likely," or "definitive," depending on the certainty of the diagnosis. Results for prenatal karyotypes typically take 10-14 days, while other karyotypes may be ready within 3-7 days. Healthcare providers typically review the results with the patient, and a genetic counselor may provide further explanation and support, particularly if a significant finding is identified.

Author: Kathleen Fergus, MS, LCGC, a board-certified genetic counselor.