Pedigree

Definition and Importance

Pedigrees are low-cost, effective tools that highlight risk for genetic/genomic conditions and facilitate accurate diagnosis.

In addition, pedigrees can help establish a diagnosis, illuminate inheritance patterns, identify at-risk family members, differentiate genetic from other risk factors, and support management decisions.

Pedigrees can also aid in establishing rapport, facilitate decision making, and clarify misconceptions, serving as both a valuable diagnostic tool and also as an important educational tool (Bennett, 2010).

Creating a Three Generation Pedigree

A basic medical pedigree (Figure X-1) usually includes a minimum of three generations. This includes the individual seeking consultation or care and his/her first degree relatives (i.e., parents, children, siblings), second degree relatives (i.e., half siblings, grandparents, aunts and uncles, grandchildren), and third degree relatives (i.e., cousins, great-grandparents, great-grandchildren).

Figure X-1 | Sample of relationship lines used in constructing a three-generation pedigree

The three-generation pedigree provides a graphic depiction or map of how family members are biologically related to each other, from one generation to the next; social and legal relationships can also be shown (e.g., adoption and divorce). This depiction utilizes a variety of standardized figures that illustrates sex, family relationships, status (alive/deceased), and medical history.

The pedigree, unlike written information, provides a visual display of the health history of the proband or consultand Opens in new window as well as other family members and includes information from both the maternal and paternal lineage if known. It also provides a visualization of disease patterns that may exist among multiple members and generations.

The pedigree can serve to clarify any genetic tests that were found to be positive (e.g., autosomal dominant Opens in new window, autosomal recessive Opens in new window, X-linked Opens in new window), including the carrier status Opens in new window of an individual and whether the status of the individual or family member is asymptomatic or presymptomatic.

The consultand or proband Opens in new window is one of several standardized terms used when conducting a pedigree that define the individual who is undergoing the family history Opens in new window.

The consultand is the individual seeking genetic counseling. This person is identified on the pedigree by an arrow, so that s/he can be easily identified when referring to the pedigree.

If more than one person (consultands) come to the appointment (such as two sisters), each person should be identified with an arrow on the pedigree.

The consultand can be healthy or a person with medical conditions but not currently diagnosed with a condition warranting evaluation. The proband, on the other hand, is the affected individual that brings the family to medical attention.

A pedigree is meaningless if the symbols cannot be interpreted from clinician to clinician. Use of the pedigree for risk assessment requires the knowledge of standardized human pedigree nomenclature and symbols (Table X-1) important in ensuring consistent history data for interprofessional collaboration and referral and to communicate accurate information to reduce errors in interpretation.

Thus, standardized symbols should always be used when constructing a pedigree. The pedigree should clearly provide information on social and legal relationships (e.g., adoption, divorce), deaths, pregnancy, pregnancy termination, and use of assistive reproductive technologies if applicable (Table X-1).

Table X-1 | Standardized Pedigree Symbols and Relationship Lines Commonly Used in Family History.

Each family member within the pedigree is recorded using the appropriate symbol noted as a square (male) or a circle (female) to depict sex and connect these gender-related symbols, using the appropriates line to each symbol to display the relationship between each member to that of the family.

If a female is pregnant, a pregnancy is represented as a box or circle depicting sex of the fetus if known with a letter ‘P’ inside. A diamond can also be used when sex of the pregnancy is unknown or noted by placing an n inside.

The diamond symbol on the pedigree can also be used for a transgendered person or persons with congenital disorders of sexual development (e.g., chromosoamal, gonadal, or anatomic).

In chromosomal abnormalities the karyotype Opens in new window is placed below the diamond symbol, for example, 46XY. The various pedigree symbols related to pregnancy, spontaneous abortion, termination of pregnancy, and infertility are also depicted in Table X-1.

A relationship in a pedigree is depicted by a horizontal line between two individuals. This relationship is used most often to denote marital status. A slash or break in that line indicates separation or divorce. A consanguineous couple Opens in new window is usually connected by a double relationship line.

The sibship line is depicted as a horizontal line that connects siblings, brothers and sisters. The difference between sibship and partner relationship lines is that each siblings has a vertical individual line attached to the horizontal line above the individual’s symbol. Examples of family relationships within the pedigree and relationship lines are depicted in Figure X-2.

Figure X-2 | Relationship lines used in constructing a three-generation pedigree.

Generations are displayed on the pedigree vertically. The line of descent is a vertical bridge connecting the horizontal sibship line to the horizontal relationship line.

A minimum of three generations for both the maternal and paternal lineage should be drawn to provide a thorough pedigree that can be useful in identifying patterns of Mendelian disorders Opens in new window or familial related disorders associated with chronic diseases indicating genetic and environmental factors.

It also may be important to record the ‘spouse’ of a family member who is not part of the kinship in the family history Opens in new window, because this information may be pertinent when attempting to establish a medical history of their offspring.

This is particularly important when a family history Opens in new window of a medical condition is identified based upon a single gene disorder to aid in determining the family lineage of inheritance.

When drawing the pedigree (or using computer programs), each generation should be on the same horizontal plane. For example, an individual’s siblings and cousins should be on the same horizontal axis.

For clarity, each generation can also be defined by designating it with a Roman numerical (see Table X-1) that is often placed on the left of the pedigree; however, the number of generations can be displayed without the Roman numerals if the pedigree is clearly constructed using appropriate symbols and placement of family members with proper relationships and a clear arrow noting the consultand or proband Opens in new window.

First names or initials, without last names, are generally recorded by the symbol for each individual to meet privacy standards. It is important to note adoption as someone who is adopted in (a couple adopts a non-biological relative) from someone who is adopted out (a biological relative who is put up for adoption by a couple).

If the person is adopted by an individual or a couple, a straight line is used to indicate a non-biological relationship, as noted in Figure X-1 .

It is not uncommon for family member to adopt a relative; for example, if a sibling adopts his or her niece or nephew, a dotted line extends from the parents to the biological relative adopting the individual to show the relationship within the family.

Documenting who is affected and who is unaffected with a disorder is crucial for risk assessment and interpretation of the pedigree. Pedigree symbols should be shaded only for affected individuals.

Different shading can be used to identify separate diseases on the pedigree. For example, when documenting a family history Opens in new window of heart disease, shading in the various quadrants of each square (male) and each circle (female) demonstrated in (Figure X-1) is a way to symbolize different presentations of heart disease within the family.

An optional way to provide clarity of individuals and family members who are disease free is to document A&W (alive and well) under each healthy individual on the pedigree.

Pertinent information about unaffected members of the family may be important when interpreting the family history Opens in new window. For example, individuals who are carriers Opens in new window of a single gene disorder but will not manifest the disease, as is the case for many recessive disorders, should be depicted on the pedigree with a symbol indicating carrier status despite the individual currently being A&W.

Family history Opens in new window information is important when assessing the spouse’s or partner’s status to determine potential genetic risk to an offspring.

These data can also provide information that may be shared by the proband or consultand Opens in new window to other family members (e.g., siblings) who may be unaffected with the disease but who also may be carriers Opens in new window; knowledge of this status can be useful regarding testing and reproductive decisions prior to conception.

Pedigrees should include ancestry of origin Opens in new window for both lineages, as well as information on pertinent medical and surgical conditions. Many genetic disorders, due to single gene mutations, are found to occur at higher rates among certain racial/ethnic groups, and the sensitivity of genetic tests depends on the correct ethnic information.

For example, sickle cell anemia Opens in new window is more common in people of African, African American, or Mediterranean heritage, and TaySachs disease Opens in new window is more likely to occur among people of Ashkenazi (eastern and central European) Jewish or French Canadian ancestry.

Understanding the role of ethnicity or ancestry-of-origins Opens in new window in disease occurrence within certain populations is important, but does not completely eliminate the disease risk in other ethnicities.

For instance, HFE-hemochromatosis, an inherited disorder that can result in iron storage disease, is more common in white populations of northern European ancestry and is highest in those of Irish ancestry of origin Opens in new window.

Although HFE-hemochromatosis is exceedingly rare in some races, such as Asians, Hispanics, African Americans, and Pacific Islanders, it has been found to occur in individuals with these ancestry-of-origins.

Generally, the pedigree is taken in a face-to-face interview with the patient, before any physical examination. A patient is usually more comfortable sharing the intimate details of his or her personal and family life while fully clothed rather than wearing one of the highly fashionable rear-exposure gowns that are available in most examination rooms.

A pedigree may also be drawn from family history questionnaires that are mailed in advance of the appointment. This information for pedigree construction can be done by hand or by computerized programs especially adapted to construct a standardized pedigree.

There are several commercial products available for constructing a pedigree. In addition, some facilities have implemented the pedigree as part of the health records. Regardless of how the pedigree is constructed, the importance of using standardized symbols and recording pertinent data are essential for accurate family history Opens in new window and risk assessment.