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13 “He Died of a Broken Heart”—Family Hearsay

13 “He Died of a Broken Heart”—Family Hearsay

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Figure 3.8



Hypothetical pedigree demonstrating how to shade affected individuals when more than one condition is segregating in a family.



63



DOCUMENTING MEDICAL EXAMINATIONS AND EVALUATIONS



Instructions:

— 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

parentheses

— If mutation known, identify in parentheses

Definition

Symbol Scenario

1. Documented evaluation (*)

Woman with negative echocardiogram.

Use only if examined/evaluated

*

*

by you or your research/clinical

E– (echo)

team or if the outside evaluation

has been reviewed and verified.

2. Carrier—not likely to manifest

disease regardless of inheritance

pattern



Male carrier of Tay-Sachs disease by patient

report (* not used because results not

verified).



3. Asymptomatic/presymptomatic

carrier—clinically unaffected at

this time but could later exhibit

symptoms



Woman age 25 with negative mammogram

and positive BRCA1 DNA test.



4. Uninformative study (u)



Eu



Man age 25 with normal physical exam and

uninformative DNA test for Huntington

disease (E2).



E+



Individual with cystic fibrosis and positive

mutation study; only one mutation has

currently been identified.



*

25 y

E1– (mammogram)

E2+ (5385insC BRCA1)



5. Affected individual with

positive evaluation (E+)



*

25 y

E1– (physical exam)

E2u (36n/18n)



E+(ΔF508)



Eu



*

E+(ΔF508/u)

10 week male fetus with a trisomy 18

karyotype.



P

*

10wk

E+(CVS)

47, XY,+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,



64



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.



PEDIGREE ETIQUETTE



65



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.

—Mark Twain



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



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