The karyotype, a study of chromosome distribution for an individual, determines chromosome numbers and chromosome structure (Chart 11.3); alterations in either of these can produce problems. The standard karyotype can be a diagnostic precursor to genetic counseling. Additional or missing pieces of most chromosomal material cause developmental problems. Despite much speculation, it is not known exactly how these abnormalities translate into structural or functional anomalies. Predictions almost always depend on comparisons with clinical findings from other similar cases that present the same evidence.

Standard chromosome studies can be helpful in evaluation of the following clinical situations:

1. Multiple malformations of structure and function

2. Failure to thrive

3. Intellectual disability

4. Ambiguous genitalia or hypogonadism

5. Infertility

6. Primary amenorrhea or oligomenorrhea

7. Delayed onset of puberty

8. Stillbirths or miscarriages (particularly with associated malformations and recurrent miscarriages)

9. Prenatal diagnosis of potential or actual abnormalities related to chromosome disorders (e.g., Down syndrome, especially in offspring of mothers older than 35 years)

10. Detection of parents with chromosomal mosaicism or translocations, who may be at high risk for transmitting genetic abnormalities to their children

11. Selected cancers and leukemias in which abnormalities of the chromosomes may reveal prognosis or disease stage

Specimens for chromosome analyses are generally obtained as follows, using aseptic procedures and special kits and containers:

1. Heparinized venous blood leukocytes from peripheral vascular blood samples are used most frequently because they are the most easily obtained. Preparation of the cells takes at least 3 days. The time required is directly proportional to the complexity of the analytic process.

2. Collect bone marrow in a green-topped tube, at least 5 mL in a heparinized syringe (20–25 U of heparin). Biopsies can sometimes be completed within 24 hours. Bone marrow analysis is often done to diagnosis certain categories of leukemias.

3. Fibroblasts from skin or other surgical specimens can be grown and preserved in long-term culture mediums for future studies. Growth of a sufficient amount of the specimen for studies usually requires at least 1 week. These specimens are especially helpful in detecting mosaicism (different chromosome constitutions in different tissues) and in the study of stillbirths, neonatal death, and spontaneous abortion.

4. Amniotic fluid in the prenatal period obtained through amniocentesis and stored in a sterile container requires at least 1 week to produce a sufficient amount of cell growth for analysis. These studies are often done for prenatal detection of chromosomal abnormalities (see Chapter 15).

5. Chorionic villus sampling (CVS) can be done at earlier stages of pregnancy (~9 weeks) than can amniocentesis. Some initial CVS studies can be done almost immediately after conception. Occasional false-positive results represent mosaicism of the placenta (the presence of several cell lines, some of which may not be found in the fetus). These studies need confirmation of findings through long-term culture (see Chapter 15).

6. Grow cells from fetal tissue or from early-trimester products of conception to determine causes of miscarriage. Cells from the fetal surface of the placenta may be easiest to grow and are the most likely to be successful.

7. Take the buccal smear, for detecting sex chromosomes, from the inner cheek and use fluorescent in situ hybridization with probes specific for the X or Y chromosome.

8. Take dried blood spot from heel of newborn.

9. Place specimens of lymph nodes or solid tumors in sterile containers.

10. Chromosome analysis is often performed using other specimens, such as skin, fascia, lung tissue, kidney, or the placenta. At least 2 mm of volume is needed for an adequate specimen.

11. See Chapter 1 guidelines for intratest care.

Many chromosomal abnormalities can be placed into one of two classes (abnormalities of number and abnormalities of structure).

1. Abnormalities of number:

   1. Autosomal:

      1. Trisomy 21 (Down syndrome)—extra chromosome 21; most common genetic condition in the United States

      2. Trisomy 18 (Edwards syndrome)—extra chromosome 18; second most common trisomy syndrome in the United States

      3. Trisomy 13 (Patau syndrome)—extra chromosome 13

   2. Sex chromosome syndromes:

      1. Turner syndrome (45, X)—affects females, characterized by short stature, webbed neck, and kidney and heart abnormalities

      2. Klinefelter syndrome (47, XXY)—affects males, characterized by hypogonadism, infertility, gynecomastia, undeveloped secondary characteristics

      3. Triple X syndrome (47, XXX)—affects females, characterized by tall stature, learning disabilities, and behavioral and emotional problems

2. Abnormalities of structure:

   1. Deletions:

      1. Cri du chat (cat’s cry syndrome): The distal part of the chromosome 5 short arm is deleted.

      2. Missing short arm of chromosome 18: 18p- is deleted.

      3. Prader–Willi syndrome: 15q is deleted in some cases.

   2. Duplications: Extra material from the second band in the long arm of the third chromosome: 3q2 trisomy (Cornelia de Lange syndrome resemblance)

   3. Translocations: Translocation of chromosomes 11 and 22: t(11;22) or 14 and 21

   4. Isochromosomes: A single chromosome with duplication of the long arm of the X chromosome: i(Xq) (a variant of Turner syndrome)

   5. Ring chromosomes: A chromosome 13 with the ends of the long and short arms joined together, as in a ring: r(13)

   6. Mosaicism: Two cell lines, one normal female and the other for Turner syndrome: 46,X; 45,X

Pretest Patient Care

1. Provide information and referrals for appropriate genetic counseling and treatment if necessary.

2. Explain the purpose, procedure, and limitations of the genetic test together with the known risks and benefits. This education process should be done by a genetic counselor.

3. Obtain a signed, witnessed consent form. This is required for most genetic tests.

4. Follow Chapter 1 guidelines for safe, effective, informed pretest care.

Normal

46 chromosomes

Women: 44 autosomes + 2 X chromosomes (karyotype 46,XX)

Men: 44 autosomes + 1 X and 1 Y chromosome (karyotype 46,XY)

A photograph of representative karyotype is included with report.