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13 “He Died of a Broken Heart”—Family Hearsay
Hypothetical pedigree demonstrating how to shade affected individuals when more than one condition is segregating in a family.
DOCUMENTING MEDICAL EXAMINATIONS AND EVALUATIONS
— E is used for evaluation to represent clinical and/or test information on the pedigree
a. E is to be deﬁned in key/legend
b. If more than one evaluation, use subscript (El, E2, E3) and deﬁne in key
c. Test results should be put in parentheses or deﬁned in key/legend
— A symbol is shaded only when an individual is clinically symptomatic
— For linkage studies, haplotype information is written below the individual. The haplotype of interest should be
on left and appropriately highlighted
— Repetitive sequences, trinucleotides and expansion numbers are written with affected allele ﬁrst and placed in
— If mutation known, identify in parentheses
1. Documented evaluation (*)
Woman with negative echocardiogram.
Use only if examined/evaluated
by you or your research/clinical
team or if the outside evaluation
has been reviewed and veriﬁed.
2. Carrier—not likely to manifest
disease regardless of inheritance
Male carrier of Tay-Sachs disease by patient
report (* not used because results not
carrier—clinically unaffected at
this time but could later exhibit
Woman age 25 with negative mammogram
and positive BRCA1 DNA test.
4. Uninformative study (u)
Man age 25 with normal physical exam and
uninformative DNA test for Huntington
Individual with cystic ﬁbrosis and positive
mutation study; only one mutation has
currently been identiﬁed.
E2+ (5385insC BRCA1)
5. Affected individual with
positive evaluation (E+)
E1– (physical exam)
10 week male fetus with a trisomy 18
Figure 3.9 How to document results of medical evaluations and genetic testing on a pedigree
(including presymptomatic testing and obligate carrier status). (Reprinted with permission from
Bennett et. al, 1995; Bennett et al., 2008.)
has been personally examined by you or you have veriﬁed information with medical
records (Figure 3.9). See Chapter 6 for speciﬁc information on how to help families
obtain medical records on relatives.
Medical evaluations on relatives can be recorded on the pedigree. Each clinical
evaluation or test can be represented by an “E” and deﬁned in the key. An evaluation
may represent information obtained by clinical examination, medical testing (e.g.,
brain imaging, biopsy, nerve conduction studies), or laboratory results. If a test or
examination result is considered abnormal it is considered a “+” (positive) result,
GETTING TO THE ROOTS: RECORDING THE FAMILY TREE
and a normal result is documented “−.” If the test is uninformative, a “u” follows the
“E.” For example, there are over 1,000 mutations in the cystic ﬁbrosis gene. A child
with known cystic ﬁbrosis may have only 1 gene mutation identiﬁed. Such a result
could be noted on the pedigree as E = F08/u (Figure 3.9).
3.16 A NOTE ON GENETIC TESTING
Genetic testing can be confusing to patients and even to many health professionals.
Some patients falsely assume that any genetic test is a chromosome test. Others
assume that all genetic testing involves direct analysis of the DNA (as compared to
enzyme analysis or tumor marker studies). A patient may assume that a genetic test
was “positive” when in fact the result is inconclusive or a gene variation of uncertain
signiﬁcance was detected. It is important to clarify how the term positive result is
being used because to a patient this may be “good news” but the health professional
may be referring to an abnormal result. It is always important to obtain documentation
of the patient’s or family member’s actual laboratory result.
3.17 THE HEALTHY PERSON WITH AN ABNORMAL GENETIC TEST
RESULT: THE DIFFERENCE BETWEEN A PRESYMPTOMATIC OR
ASYMPTOMATIC CARRIER AND AN OBLIGATE CARRIER
Advances in genetic testing now allow a healthy person to be tested for a genetic
condition that he or she may or will develop in the future. Many geneticists reserve
the description presymptomatic carrier for a healthy person who is likely to develop
the disease in his or her lifetime (Bennett et al., 1995). For example, a person who
is predicted to develop Huntington disease in his or her lifetime has a segment of
genetic material called a CAG trinucleotide repeat that is repeated too many times.
A person with 40 or more CAG repeats is likely to have symptoms of Huntington
disease by the time he or she reaches the age of 70.
In contrast, a woman who has a mutation in BRCA1 or BRCA2 (the genes associated
with two hereditary breast-ovarian cancer syndromes) has up to an 85% lifetime
chance of developing breast cancer to age 70, but the development of cancer is
not inevitable. This is usually referred to as predisposition or susceptibility genetic
testing. The description asymptomatic carrier is sometimes used for a person who
carries a susceptibility or predisposition mutation. Some geneticists take exception
to the use of the terminology predictive testing because no genetic test provides and
absolute gaze into a person’s medical future.
A person who carries a gene mutation but will not develop clinical symptoms is
referred to as an obligate carrier (Bennett et al., 1995). For example, the parents of
children affected with a classic autosomal recessive disorder are obligate carriers. A
healthy mother of two boys with an X-linked recessive condition (such as Duchenne
muscular dystrophy) is an obligate carrier. A problem with this terminology is that
the spectrum of recognizing disease expression has broadened for many diseases.
For example, women with a fragile X premutation have been traditionally thought of
as healthy obligate carriers, but it is now known that some of these women experience
premature ovarian insufﬁciency as an expression of the disease (McConkie-Rosell
et al., 2005).
Figure 3.9 demonstrates how to document genetic test results and asymptomatic
or presymptomatic and obligate carrier status. Individuals who are obligate carriers
are represented on the pedigree with a dot in the middle of the male (square) or
female (circle) symbol. Persons who are asymptomatic or presymptomatic carriers
are represented with a line down the middle of the pedigree symbol. If the person
later develops the disease, the symbol is shaded.
3.18 PEDIGREE ETIQUETTE
3.18.1 The Skeletons in the Closet
For many reasons, people tend to keep genetic information private. There is often a
sense of stigma, even embarrassment about “bad blood” or a “curse” in the family. As
Francis Galton observed, “Most men and women shrink from having their hereditary
worth recorded. There may be family diseases of which they hardly dare to speak,
and then in whispered hints or hushed phrases as if timidity of utterance could hush
thoughts. . .” (Resta, 1995). People may be reluctant to share medical and genetic
information because of fear they will be blamed for the family imperfections.
3.18.2 Choose Your Words Wisely
The difference between the right word and the almost right word is the difference
between lightening and the lightning bug.
When you take a medical-family history, you are inquiring about the very essence
of an individual. You are asking not only about the individual’s personal health but
also about intimate relationships and the health of family members (with whom he
or she may have little contact). Before you begin taking a genetic family history, it
is helpful to warn the client: “I need to ask you some personal questions about your
health and the health of people in your family. Your answers to these questions are
an important part of providing you with appropriate medical care.”
The clinician should be careful not to perpetuate feelings of guilt or fears of
stigmatization. Use words such as altered, changed, or not working properly to
describe genes, instead of mutation, bad, or faulty. Emphasize to the patient that
relatives have no choice in the genetic conditions that are passed in a family; the
diseases are nobody’s fault.
Be sensitive to terms like an uneventful pregnancy. Although a healthy pregnancy
may be uneventful to the clinician, it is very eventful to the proud parents! I often