The Principles of Clinical Cytogenetics - Extra Materials - Springer

Genetic Counseling 545
autosome, and generally do not exhibit features of the condition. Examples of conditions that follow an
X-linked recessive pattern of inheritance include fragile X syndrome, which is the most common inherited
form of mental retardation (see Chapter 18), and hemophilia, a bleeding disorder.
It should be briefly noted that, in the past, cytogenetic methods were routinely employed to test for
fragile X syndrome. Using a folate-deprived culture medium, the fragile site on the long arm of the X
chromosome associated with this condition could be expressed. Due to serious limitations of this
methodology in detecting affected individuals and carriers, molecular diagnostic testing has replaced
cytogenetic analysis for fragile X syndrome as the preferred testing method (7–9) (see Chapter 18).
In X-linked dominant inheritance, there is a 50% chance for each child of an affected woman to
inherit the disease-causing mutation. Affected females tend to be more common and are often less
severely affected than are affected males; X-linked dominant conditions, particularly those that are
rare, can be prenatally lethal in affected males. Incontinentia pigmenti type 2, which affects the skin,
skin derivatives, and central nervous system, is an X-linked dominant condition that is frequently
lethal in affected males (10).
In multifactorial inheritance, a genetic predisposition increases the chance that an individual will
develop a particular condition. Certain environmental factors, such as diet and exercise, also have a
role in determining if the individual will be affected. Examples of multifactorial conditions are diabetes,
heart disease, and neural tube defects. Generally speaking, the more distant the degree of relationship
between the individual in question and the affected relative, the lower the recurrence risk,
until such risk approximates that of the general population.
Personal or Family History of Cancer
In the majority of cases, cancer is sporadic in an individual. However, in some families, a genetic
predisposition to cancer significantly increases the chance to develop the condition. Hallmarks of
hereditary cancer families include relatively early-onset cancer as compared to the general population,
bilateral or multi-organ cancer, multiple affected family members (usually following an autosomal
dominant pattern of inheritance), and unusual cancer or the presence of certain characteristic
clinical features. When an individual is referred for cancer genetic counseling, the genetic counselor
educates the counselee about the genetics of cancer predisposition. Based on personal and family
history information, the counselor also provides a risk assessment for cancer or for a hereditary cancer
predisposition. The risks, benefits, and limitations of appropriate, available molecular testing
options and research opportunities are discussed, as are the potential results and their possible psychosocial
and practical implications. Options for cancer risk reduction, such as prophylactic surgery,
chemoprevention, and cancer screening, are also likely to be reviewed.
As discussed in Chapter 15, certain translocations are characteristic of certain cancers. For
example, the (9;22) translocation, which results in the “Philadelphia chromosome,” and the fusion of
two genes, BCR and ABL, is associated with chronic myelogenous leukemia (CML). Similarly,
Burkitt’s lymphoma is associated with an (8;14) translocation. The identification of cytogenetic
abnormalities in a cancer patient can have important diagnostic and prognostic implications and can
also play a role in designing a treatment strategy (10,11). Occasionally, when chromosome analysis
is performed for the indication of a hematological abnormality, a chromosome abnormality that might
be constitutional is identified. In such a situation, this should be verified, and, if true, the patient
should be counseled about the finding and the associated implications, not only for him or herself but
for other family members as well (11).
Consanguinity
When both members of a couple share at least one common ancestor, they should be referred to a
genetic counselor to discuss the possibility for an increased risk of birth defects and/or genetic conditions
in their offspring. Using information about the degree of relationship between the members of