The Genetic Family History

The personal and family medical pedigree has evolved from its earliest ancestors in the 15th century to its current form and has become an essential tool in many aspects of the clinical genetics evaluation. Originally used primarily to display relationship information, the pedigree was used for the first time to demonstrate inheritance of traits in the mid-19th century when Pliney Earl published on inheritance of color blindness and Francis Galton described inheritance of artistic ability and genius.1

Symbols used to document pedigree information have varied, often depending on personal, professional, or national preferences. The key to functionality for pedigrees, however, is the degree to which they are able to communicate information uniformly to all users. In 1993, a task force of the National Society of Genetic Counselors surveyed genetic counselors regarding interpretation of pedigree symbols and conformity of usage.2 As many as 17 different symbols were used to depict pregnancy, with 16 different symbols being used to denote miscarriage; in both cases, symbols sometimes had several meanings to different users. It became evident that standardization of symbol usage was needed. The group established a recommended nomenclature for pedigrees, which was published in the American Journal of Human Genetics in 1995.3

The currently recommended methods for documenting pedigree information including symbols, spatial relationships, and clinical/investigative status are detailed in Figures 4-1 through 4-5. These standards allow recording of traditional relationships as well as those developing as new technologies are applied, particularly in reproductive medicine. They also serve as a uniform baseline for future additions or modifications as the field continues to evolve.

These pedigrees now form the cornerstone for determination of diagnosis, pattern of inheritance, and recurrence risk.4 Use of pedigree information can impact overall risk assessment, medical management decisions, and feasibility of various testing strategies. In addition, collection of family medical information has aided in the understanding of many unique features of hereditary disorders, including natural history, variability, and gene-gene or gene-environment interactions.

Collection of a family pedigree represents an opportunity to build a relationship with the patient and family and to learn about how the family functions.4 As the genetic counselor or other healthcare provider explains the purpose of the family history, an atmosphere of open communication and respect can be established. This process provides a window to the social relationships and psychosocial and educational needs of patients and families. In the social sciences, genograms are used to graphically depict family dynamics that influence individual behaviors.5 This information is also essential for successful counseling of patients in the clinical genetics setting, and while not always recorded in the same fashion, it is a vital part of the process of pedigree gathering. Observations about coping mechanisms, assumptions about disease causation, family hierarchy, key life experiences, stress levels, body language, and religious and ethnic influences all are integrated into consideration about the most effective ways to communicate information about a diagnosis, prognosis, or management plan to patients and families.

Ideally, the pedigree is collected in a face-to-face session. This is usually done prior to or at the beginning of the clinical genetics evaluation, but may be done later, particularly when evaluating a pregnancy or a newborn with an unanticipated, newly diagnosed condition. It is helpful to provide patients with advance notice about the nature of information to be collected, as this facilitates accuracy and completeness. At a minimum, a three-generation pedigree should be collected, including all first-degree relatives (parents, children, full siblings), second-degree relatives (grandparents, aunts, uncles, nieces and nephews, half-siblings, grandchildren), and as pertinent, many third-degree relatives (cousins, great-aunts, great-uncles, great-grandparents). This group can be expanded or condensed, depending on the nature of the referral and patient responses to preliminary questioning about features


—Key should contain all information relevant to interpretation of pedigree (e.g., define shading) —For clinical (nonpublished) pedigrees, include:

a) family names/initials, when appropriate b) name and title of person recording pedigree c) historian (person relaying family history information)

d)date of intake/update

—Recommended order of information placed below symbol (below to lower right, if necessary):

a) age/date of birth or age at death b) evaluation (see Figure 4-5)

c) pedigree number (e.g., I-1, I-2, I-3)



Sex Unknown


1. Individual




30 y

6 4 mo

Assign gender by phenotype.

2. Affected individual


Key/legend used to define shading or other fill (e.g., hatches, dots, etc.).



With>2 conditions, the individual's symbol should be partitioned accordingly, each segment shaded with a different fill and defined in legend.

3. Multiple individuals, number known



Number of siblings written inside symbol. (Affected individuals should not be grouped.)

4. Multiple individuals, number unknown




"n" used in place of "?"

5a. Deceased individual




2 . 4 mo


Use of cross (f ) may be confused with symbol for evaluated positive (+). If known, write "d." with age at death below symbol.

5b. Stillbirth (SB)


SB 8 w


£ 0 wk

$ 34 wk

Birth of a dead child with gestational age noted.

6. Pregnancy (P)

LMP: 7/1/94

20 wk


Gestational age and karyotype (if known) below symbol. Light shading can be used for affected and defined in key/legend.

7a. Proband



First affected family member coming to medical attention.

7b. Consultand


Individual(s) seeking genetic counseling/testing.

Figure 4-1. Common pedigree symbols, definitions, and abbreviations. (Figures 4-1 to 4-5 reprinted from Bennett RL, Steinhaus KA, Uhrish SB, et al."Recommendations for standardized human pedigree nomenclature." American Journal of Human Genetics 1995;56:745-752, with permission from the University of Chicago Press.)

Figure 4-1. Common pedigree symbols, definitions, and abbreviations. (Figures 4-1 to 4-5 reprinted from Bennett RL, Steinhaus KA, Uhrish SB, et al."Recommendations for standardized human pedigree nomenclature." American Journal of Human Genetics 1995;56:745-752, with permission from the University of Chicago Press.)


— Symbols are smaller than standard ones and individual's ling is shorter. (Even if sex is known, triangles are preferred to a small square/circle; symbol may be mistaken for symbols 1, 2, and 5a/5b of Figure 1, paricularly on hand-drawn pedigrees.)

— If gender and gestational age known, write below symbol in that order.


— Symbols are smaller than standard ones and individual's ling is shorter. (Even if sex is known, triangles are preferred to a small square/circle; symbol may be mistaken for symbols 1, 2, and 5a/5b of Figure 1, paricularly on hand-drawn pedigrees.)

— If gender and gestational age known, write below symbol in that order.



Sex Unknown


1. Spontaneous abortion (SAB)

male male



If ectopic pregnancy, write ECT below symbol.

2. Affected SAB


female female

16 wk

If gestational age known, write below symbol. Key/legend used to define shading.

3. Termination of pregnancy (TOP)


female female


Other abbreviations (e.g., TAB, VTOP, Ab) not used for sake of consistency

4. Affected TOP




Key/legend used to define shading.

Figure 4-2. Pedigree symbols and abbreviations for pregnancies not carried to term.

Figure 4-2. Pedigree symbols and abbreviations for pregnancies not carried to term.



1. relationship line o

3. sibship line

2. line of descent

4. individual's lines

If possible, male partner should be to left of female partner on relationship line

Siblings should be listed from left to right in birth order (oldest to youngest).

For pregnancies not carried to term (SABs and TOPs), the individual's line is shortened.

1. Relationship line (horizontal) a. Relationships b. Consanguinity

A break in a relationship line indicates that the relationship no longer exists. Multiple previous partners do not need to be shown if they do not affect genetic assessment.

If the degree of relationship is not obvious from pedigree, it should be stated (e.g., third cousins) above relationship line.

2. Line of descent (vertical or diagonal) a. Genetic

- Twins

- Family history not available/known for individual

- No children by choice or reason unknown

- Infertility b. Adoption o

Biologic parents shown.




A horizontal line between the symbols implies a relationship line.

o q.q vasectomy tubal or

Indicate reason, if known.

Indicate reason, if known.

azoospermia endometriosis out by relative

by relative

Brackets used for all adoptions. Social vs. biological parents denoted by dashed and solid lines of descent, respectively.

Figure 4-3. Pedigree line definitions.


— If the woman is both the ovum donor and a surrogate, in the interest of genetic assessment, she will be referred to only as a donor (e.g., 4 and 5)

— The pregnancy symbol and its line of descent are positioned below the woman who is carrying the pregnancy.

— Family history can be taken on individuals, including donors, where history is known.

Possible reproductive scenarios


1. Sperm donor

Couple in which the woman is carrying preg-mancy using donor ssperm. No relationship line is shown between the woman carrying the pregnancy and the sperm donor. For a lesbian relationship, the male partner can be substituted with a female partner.

2. Ovum donor

Couple in which the woman is carrying pregnancy using donor egg(s) and partner's sperm.

3. Surrogate only

Couple whose gametes are used to impregnate another woman (surrogate) who carries the pregnancy.

4. Surrogate ovum donor

Couple in which the male partner's sperm is used to inseminate (a) an unrelated woman or (b) a sister who is carrying the pregnancy for the couple.

5. Planned adoption

Couple contracts with a woman to carry a pregnancy using the ovum of the woman carrying the pregnancy and dono sperm.

Figure 4-4. Assisted reproductive technologies symbols and definitions.

Figure 4-5. Pedigree symbolization of genetic evaluation/ testing information.


— Evaluation (E) is used 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 (E-|, E2, E3) and define in key. May be written side by side or below each other depending on available space.

c. Test results should be put in parentheses or defined in key/legend.

d. If results of exam/family study/testing not documented or unavailable, may use a question mark (e.g.,"E?").

a. Asterisk is placed next to lower right edge of symbol b. Use only if examined/evaluated by you or your research/clinical team or if the outside evaluation has been personally reviewed and verified

— A symbol is shaded only when an individual is clinically symptomatic.

— For linkage studies, haplotype in formation is written below the individual. The haplotype of interest should be on the left and appropriately highlighted.

— Repetitive sequences, trinucleotides, and expansion numbers are written with affected allele first and placed in parentheses.

— If mutation known, identify and place in parentheses.

— Recommended order of information:

a. Age/date of birth or age at death b. Evaluation information c. Pedigree number (e.g., I-1, I-2, I-3)





1. Documented evaluation (*)


Woman with normal physical exam and negative fragile X chromosome study (normal phenotype and negative test result).

E -

2. Obligate carrier (will not manifest disease)


Woman with normal physical exam and premutation for fragile X (normal phenotype and positive test result).

à E+(100n/35n)

3. Asymptomatic/ presymp-tomatic carrier (clinically unaffected at this time but could later exhibit symptoms)


Man age 25 with normal physical exam and positive DNA test for Huntington disease (symbol filled in if/when symptoms develop).


4. Uninformative study (u)

à Eu

Man age 25 with normal physical exam and uninformative DNA test for Huntington disease (E1) and negative brain MRI study (E2). 1


5. Affected individual with positive evaluation (E+)


Individual with cystic fibrosis and positive mutation study, although only one mutation has currently been identified.


18- week male fetus with abnormalities on ultrasound and a trisom 18 karyotype.

18wk* E+(tri 18n)

relevant to the reason for referral. For example, cancer genetic evaluations may necessitate a more extended family pedigree, while a brief, focused pedigree may suffice when discussing cystic fibrosis carrier testing.

Information that should be collected about each individual in the pedigree is listed in Table 4-1. This, too, may be modified to reflect the nature of the diagnosis under investigation. Ethnicity, consanguinity, and unique biological relationships should be recorded using standard notation. All reported diagnoses or conditions ideally should be confirmed through authorized request and review of medical records. Key records to obtain include pathology reports, test results (particularly for any genetic testing that has been performed), imaging reports, and autopsy reports. In the absence of these documents,family genealogies or death certificates may provide some degree of verification of reported information.

An emerging issue in the use of pedigrees for clinical evaluations and research is the issue of individual confidentiality.6,7 Each member of the family has a right to expect that medical information will remain confidential. This becomes complicated when one considers the pedigree that may contain both reported ("hearsay") and confirmed information for numerous individuals. Those people may have willingly shared information with the patient but may not want it shared with other family members. If subsequent to an evaluation a patient requests release of his or her pedigree to another family member, a provider should carefully consider the question of ownership of the pedigree information and be attuned to the potential consequences of releasing the (identifiable) information about other family members. Current interpretation of regulations outlined in the Health Insurance Portability and Accountability Act (HIPAA) and other medical records privacy legislation may influence how such information is shared.8 Professional organizations including the American Society of Human Genetics also have developed position statements on this issue.9

Table 4-1. Family History Collection: What to Ask? For All Family Members

Current age;complete date of birth Exact relationship to proband General health status History of major acute or chronic illness History of learning problems, diagnosed disabilities, or mental retardation

Highest grade level completed (when relevant) Employment (when relevant)

Reproductive history, including pregnancies, miscarriages, elective terminations, infertility, and choice not to have children

Gestational age and last menstrual period for ongoing pregnancies Consanguinity

Targeted questions relevant to the reason for evaluation, for example, key symptoms or features of the condition in question, pertinent evaluations, etc. Age at death; year of death; cause of death

For Family Member Known to Be Affected by the Condition in Question


Age at diagnosis

Method of diagnosis

Evaluations and testing completed


Information about ongoing treatment or management plan Availability of medical records for review

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