Am. J. Hum. Genet. 56:745-752, 1995

Recommendations for Standardized HumanPedigree NomenclatureRobin L. Bennett,' Kathryn A. Steinhaus,5 Stefanie B. Uhrich, Corrine K. O'Sullivan,' Robert G. Resta,Debra Lochner-Doyle,4 Dorene S. Markel,6 Victoria Vincent,7 and Jan Hamanishi2

'Division of Medical Genetics and 2Department of Obstetrics and Gynecology, University of Washington Medical Center, and 3Center for Perinatal Studies,Swedish Medical Center, and Genetics Services Center, Department of Health, Seattle; 'Division of Human Genetics, University of California,Irvine, Orange; 6Human Genome Center, University of Michigan, Ann Arbor, and 7Division of Genetics, University of South Carolina Schoolof Medicine, Columbia

Summary

The construction of an accurate family pedigree is a funda-mental component of a clinical genetic evaluation and ofhuman genetic research. Previous surveys of genetic coun-selors and human genetic publications have demonstratedsignificant inconsistencies in the usage ofcommon pedigreesymbols representing situations such as pregnancy, termi-nation of pregnancy, miscarriage, and adoption, as wellas less common scenarios such as pregnancies conceivedthrough assisted reproductive technologies. The PedigreeStandardization Task Force (PSTF) was organized throughthe Professional Issues Committee of the National Societyof Genetic Counselors, to establish recommendations foruniversal standards in human pedigree nomenclature. No-menclature was chosen based on current usage, consis-tency among symbols, computer compatibility, and theadaptability of symbols to reflect the rapid technical ad-vances in human genetics. Preliminary recommendationswere presented for review at three national meetings ofhuman genetic professionals and sent to >100 humangenetic professionals for review. On the basis of this reviewprocess, the recommendations of the PSTF for standard-ized human pedigree nomenclature are presented here. Byincorporating these recommendations into medical genet-ics professional training programs, board examinations,genetic publications, and pedigree software, the adoptionof uniform pedigree nomenclature can begin. Usage ofstandardized pedigree nomenclature will reduce thechances for incorrect interpretation of patient and familymedical and genetic information. It may also improve thequality of patient care provided by genetic professionalsand facilitate communication between researchers in-volved with genetic family studies.

Received October 3, 1994; accepted for publication November 28,1994.Address for correspondence and reprints: Robin L. Bennett, Medical

Genetics, RG-25, University of Washington Medical Center, Seattle, WA98195.X) 1995 by The American Society of Human Genetics. All rights reserved.0002-9297/95/5603-0025$02.00

Introduction

The construction of an accurate family pedigree is funda-mental to the provision of clinical genetic services andserves as an informational framework for human geneticresearch. Review of a family pedigree aids the clinician indiagnosis, helps establish the pattern of inheritance, andassists in identifying persons at risk. The pedigree alsoserves as a reference of social and biological relationshipsto alert the clinician to issues of blended families, adoption,deaths, pregnancy termination, and pregnancies conceivedby assisted reproductive technologies. Correct interpreta-tion of family pedigrees is essential for human genetic re-search and is particularly challenging when reviewing pedi-grees diagrammed within professional publications orwhen research teams collaborate to study large families.Pedigree analysis also facilitates the identification of disor-ders where genetic mechanisms such as anticipation, mito-chondrial inheritance, X-linked or dominant homozygouslethality, and differential age at onset, based on the sex ofthe transmitting individual, are factors.

Although one might assume that pedigree nomenclatureis used in a universal fashion, we have demonstrated widevariation among genetics professionals, both in clinicalpractice and in professional publications. A survey of mem-bers of the National Society of Genetic Counselors (NSGC)showed discrepancies even in common symbols used torecord a genetic family history (i.e., pregnancy, miscarriage,abortion, termination of pregnancy, adoption) (Bennett etal. 1993). No consensus was noted in recording situationsrepresenting assisted reproductive technologies (i.e., artifi-cial insemination by donor semen, donor ovum, surrogatemotherhood). A review of24 standard medical genetic text-books and publications in 10 current human genetic jour-nals further demonstrated wide variation in pedigree con-struction (Steinhaus et al., in press). Historical studies havealso shown a lack of consistency in pedigree symbolsthroughout the 20th century (Resta 1993).

Standardization of pedigree nomenclature is important,much as it was useful to develop universal cytogenetic no-menclature (Paris Conference 1971). The Pedigree Stan-dardization Task Force (PSTF) was established through the

745

Am. J. Hum. Genet. 56:745-752, 1995

Professional Issues Committee of the NSGC to addressthis issue and to make recommendations for standardizedhuman pedigree nomenclature. The recommendations ofthe PSTF are presented here.

Material and Methods

A draft of proposed pedigree nomenclature was devel-oped by reviewing symbols and abbreviations used by ge-netic counselors in clinical practice, on the basis of 437questionnaire responses by NSGC members (Bennett et al.1993). Pedigree nomenclature in professional human ge-netic publications, including current journal articles and

standard human genetic textbooks, was also reviewed(Steinhaus et al., in press). In addition to frequent usage,consistency among symbols, computer compatibility, andability to adapt to the rapid changes in human geneticswere considered.A peer review of the proposed pedigree nomenclature

was conducted. A first draft of proposed symbols was circu-lated to a liaison committee that included representativesfrom the NSGC, the American Board of Medical Genetics,the American Society of Human Genetics (ASHG), theAmerican Board of Genetic Counseling, the WashingtonState Department of Health, editors of various genetic pub-lications, the Education Committee of the Council of Re-

Instructions:- Key should contain all information relevant to interpretation of pedigree (e.g., define shading)- For clinical (non-published) pedigrees, include:

a) family names/initials, when appropriateb) name and title ofperson recording pedigreec) historian (person relaying family history information)d) date of inake/update

- Recommended order of information placed below symbol (below to lower right, if necessary):a) age/date of birth or age at deathb) evaluation (see Figure 5)c) pedigree number (e.g., I-I, I-2, 1-3)

SexMale Female Unknown Comients

1. Individual 7 5 7 Assign gender by phenotype.

b. 1925 30y 4mo

2. Affected individual 7id7 Key/legend used to define shading or other fillV (e.g., hatches, dots, etc.).

AL-- - -i zWith .2 conditions, the individual's symbolI1iJ UJw < E should be partitioned accordingly eac segmentshaded with a different fill and defined in legend.

3. Multiple individuals, F 7 Number of siblings written inside symbol.number known Lii 0) \% (Affected individuals should not be grouped.)

4. Multiple individuals, %, 7- -7K-Y "n" used in place of 'ir =ark.number unknown C) \

0d. 4m

SB30wk

i(s) seeking genetic counseling/testing.

5a. Deceased individual

5b. Stillbirth (SB)35y

SB

28 wk

SB34 wk

Use of cross (t) may be confused with symbolfor evaluated positive (+). Ifknown, write "d."with age at deat below symbolsBirth of a dead child with gestational age noted.

Figure I Common pedigree symbols, definitions, and abbreviations

i

746

Bennett et al.: Standardized Pedigree Nomenclature

Instructions:Symbols are smaller than standard ones and individual's line is shorter. (Even if sex is known, trianglesare preferred to a small square/circle; symbol may be mistaken for symbols 1, 2, and 5a/5b of Figure 1,particularly on hand drawn pedigrees.)If gender and gestational age known, write below symbol in that order.

SexMale Female Unknown Comments

1. Spontaneous abortion /\7 /\ 7 If ectopic pregnancy, write ECT below symbol.(SAB) male ECT

2. Affected SAB |A7 7 If gestational age known, write below symbol.male female 16 wk Key/legend used to define shading.

3. Termination of 7 > 7|ia 7 $7 |Other abbreviations (e.g., TAB, VTOP, Ab)pregnancy (TOP) male female not used for sake of consistency.

4. Affected TOP 7 7 7 Key/legend used to define shading.male female

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

gional Genetics Networks (CORN), the Adoption Subcom-mittee of CORN, the Alliance of Genetic Support Groups,and the International Society of Nurses in Genetics. Theresulting recommendations were presented in poster formatat the 1993 annual education conferences of the NSGC inAtlanta and the ASHG in New Orleans, allowing partici-pants at these meetings the opportunity to provide bothverbal and written response to the PSTF. After incorpora-tion of reviewer commentary, a revision was presented asa poster at the 1994 joint meeting of the March of DimesEducation Conference and the American College of Medi-cal Genetics (ACMG) in Kissimmee, FL, again allowing anopportunity for comment by practicing genetic profession-als. A third revision of the pedigree nomenclature was sent,in April 1994, to -120 genetic professionals, includingjournal editors, chairs of the major professional geneticsocieties and organizations (including the newly formedACMG), directors of genetic counseling training programs,authors of standard human genetic textbooks, and otherleaders in the field of human genetics. The proposed no-menclature was field-tested by small focus groups, includ-ing members of the Education Committees of the PacificNorthwest Regional Genetics Group and the Pacific South-west Regional Genetics Group, and master's-level geneticcounseling students at the University of Wisconsin. Afourth revision was distributed in July 1994 to -70 geneticprofessionals from the original list of 120. Minor revisionswere made in this fourth draft, which was then submittedto, and approved by, the PSTF liaison members.

Results

The NSGC PSTF's recommendations for symbolizationof a genetic family history are outlined in figures 1-5.These recommendations apply both to unpublished clinicalpedigrees and to research publication, once identifying in-

formation (i.e., birthdates, names) has been removed. Theappendix and figure 1A provide an example of a hypotheti-cal clinical history and a pedigree utilizing the recom-mended pedigree nomenclature, to illustrate the relation-ship of symbols to each other and the placement of infor-mation on the pedigree.

Discussion

The pedigree is the symbolic language of clinical geneticservices and of human genetic research. In this age of in-creasing information exchange, standardization of the lan-guage of the human pedigree is essential for clear communi-cation among medical professionals and genetic research-ers. As with the development of cytogenetic nomenclature,the development of uniform pedigree nomenclature is anevolving process. The utility and the effectiveness of theproposed pedigree nomenclature need to be evaluated inthe future. Plans for assessment include review of geneticpublications, in a few years time, to determine whether thesymbols are indeed being used by the authors. In addition,a sample of members of the professional genetics organiza-tions can be surveyed about the value of the pedigree-nomenclature guidelines in their clinical practice and re-search.

There are several methods for incorporating standard-ized pedigree nomenclature into practice. Teaching uniformpedigree symbols in human genetic professional trainingprograms, in medical and nursing schools, and to alliedhealth professionals, as well as including standard pedigreenomenclature in board examinations, will encourage thenext generation of health-care providers to integrate thisnomenclature into their routine. If genetic diagnostic labsrequire standardized pedigrees on their intake and re-porting forms, this may improve communication betweenthe laboratory and referring health professional. Computer

747

Am. J. Hum. Genet. 56:745-752, 1995

Definitions Comments1. relationship line If possible, male partner should be to left of female partner

I on relationship line.

3. sibshilp i 2. line of descent Siblings should be listed from left to right in birth order(oldest to youngest)

For pregnancies not carried to term (SABs and TOPs),4. individual's lines the individual's line is shortened.

1. Relationship line (horizontal)a. Relationships A break in a relationship

line indicates the relation-ship no longer exists.Multiple previous partnersdo not need to be shown ifthey do not affect geneticassessment.

b. Consanguinity If degree of relationship not obvious from pedigree, it shouldL....JVJ be stated (e.g., third cousins) above relationship line.

2. Line of descent (vertica. Genetic

Twins

Family history notavailable/knownfor individual

No children bychoice or reasonunknown

Infertility

x1 or diagonal)

Monozygotic Dizygo

±, A

I2i-- ._b

- .4

b. Adoption in

Biologic parents shown.

)tic Unknown A horizontal line between the symbols implies- - -a relationship line.

Oor9

vasectomy tubal

;Ior9azoospermia endometriosis

out by relat

Indicate reason, iifknown.

Indicate reason, if known.

Live Brackets used for alladoptions. Social vs.

biological parents| \J ,XJ denote ydse n

solid lines of descent,respectively.

Figure 3 Pedigree line definitions

programs that incorporate uniform symbols for recordingfamily histories would be useful. Editors of genetic publica-tions should be encouraged to include standardized pedi-gree nomenclature in their journals' information for con-tributors and in textbooks.

Of equal importance to the development of standard-ized pedigree symbolization is the development of pro-fessional guidelines regarding ethical issues in recordinga clinical genetic family history, as well as in publicationof pedigrees. For instance, in figure 5, example 3, the

--I

748

Bennett et al.: Standardized Pedigree Nomenclature

suggested symbol for an asymptomatic/presymptomaticcarrier (e.g., a person with no clinical symptoms of Hun-tington disease who carries the mutation) is shown, butit could be argued that, for confidentiality reasons, pre-symptomatic test results should not be recorded on the

pedigree or even in the patient chart. Likewise, largepedigrees are published in research papers where an indi-vidual could be identified from the family structure, ge-netic condition, and the names of the researchers,yet consent for publication may not have been ob-

Definitions:- Egg or sperm donor (D)- Surrogate (S)- If the woman is both the ovum donor and a surrogate, in the interest of genetic assessment, she will only be

referred to 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, inclu ing donors, where history is known.

Possible Reproductive Scenarios Comments1. Sperm donor Couple in which woman is carrying preg-

D)D0gT O i1 nancy using donor sperm. No relationshipline is shown between the woman carrying

or the pregnancy and the sperm donor. For alesbian relationship, the male partner canP P'T be substituted with a female partner.

2. Ovum donor Couple in which woman is carrying preg-D} A) nancy using donor egg(s) and partner's

sperm.

3. Surrogate only Couple whose gametes are used to impreg-S-)(i) nate another woman (surrogate) who

carries the pregnancy.

P

4. Surrogate a) b) Couple in which male partner's sperm isovum donor used to inseminate a) an unrelated woman

D D ~~~~~~~~~~orb) a sister who is carrying the pregnancyfor the couple.

or

5. Planned Couple contracts with a woman to carry aadoption [D pregnancy using ovum of the woman

carrying the pregnancy and donor sperm.

[a ]

Figure 4 Assisted-reproductive-technologies symbols and definitions

749

Instructions:- Evaluation (E) is used to represent clinical and/or test information on the pedigree.

a. E is to be defined in key egend.b. If more than one evaluation, use subscript (E1, 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?).

- Documented evaluation (*)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 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 and place in parentheses.- Recommended order of information:

1) age/date of birth or age at death2) evaluation information3) pedigree number (e.g., I-1, 1-2, 1-3)

Definition Symbol Scenario Example1. Documented 7 Woman with normal physical exam and

evaluation (*) ( ) negative fragile X chromosome study (nor-mal phenotype and negative test result). *

2. Obligate carrier (will not Woman with normal physical exam andmanifest disease). 7 premutation for fragile X (normal pheno- *

x~-~' type and positive test result). E+(x1 *35n)3. Asymptomatic/presymp- _ Man age 25 with normal physical exam

tomatic carrier (clinically III and positive DNA test for Huntingtonunaffected at this time disease (symbol filled in if/when symp-but could later exhibit toms develop).symptoms)

25 y

E+(45n/18n)4. Uninformative study (u) 7 Man age 25 with normal physical exam

U l and uninformative DNA test for Hunting-Eulton disease (E1) and negative brain MRI 25 y*Eu study (E2). Elu(36n/18n)

E2.5. Affected individual with 7 Individual with cystic fibrosis and posi-

positive evaluation (E+) tive mutation study, although only onemutation has currently been identified. E+(AF508 Eu

E+

E+(AF508/u)

18 week male fetus with abnormalitieson ultrasound and a trisomy 18 karyotype.

18 wkE+(tri 18)

Figure 5 Pedigree symbolization of genetic evaluation/testing information

Bennett et al.: Standardized Pedigree Nomenclature

tained from each person who is symbolized on the pedi-gree.

The development of ethical guidelines about the type ofinformation recorded on a pedigree should be considered.For example, information that is commonly recorded on a

pedigree (e.g., same-sex relationships, suicide, alcoholism,HIV status, marital status, pregnancy terminations) may

or may not be helpful in making a clinical diagnosis andgenetic-risk assessment; however, this type of information,if released to a third party (e.g., insurer, employer), may beused in a discriminatory fashion. The kind of informationdocumented on a pedigree also raises issues of protectionof privacy when a family pedigree is exchanged betweenhealth professionals evaluating different members of an

extended family. The pedigree may contain information notprivy to the other relatives (e.g., nonpaternity, pregnancy

terminations, affected status, pregnancies conceived by as-

sisted reproductive technologies, etc.). Researchers and cli-

nicians need to weigh carefully patient confidentialityagainst clinical and genetic relevance when deciding whatinformation to include on a pedigree.The professional genetics community should continue to

explore the many ethical and legal dilemmas surroundingthe clinical and research use of the family pedigree, to as-

sure the protection of confidentiality of our patients andsubjects. A conference sponsored by the American Associa-tion for the Advancement of Science (AAAS)-AmericanBar Association (ABA) National Conference of Lawyersand Scientists, and the AAAS Committee on Scientific Free-dom and Responsibility met to address some of the issuesinvolved in pedigree research but did not arrive at a consen-

sus (Frankel and Teich 1993). The Council of BiologicalEditors has also raised the issue of protection of privacyfor individuals in published pedigrees (Glass et al. 1994).Problems such as misuse of published information, leadingto job loss and problems of obtaining life insurance, were

addressed. Solutions such as altering or omitting symbolsto disguise the family and obtaining consent from eachperson in a published pedigree were discussed, but no

agreement was reached. The professional human geneticssocieties may wish to consider the development of policystatements to address the issues of confidentiality for sub-jects in clinical and research pedigrees.

This document is the result of the thoughtful input frommany professionals in the genetics community. It is impossi-ble to develop uniform pedigree nomenclature without cre-

ating controversy. The problem is succinctly stated by Fran-ces Galton (1889, p. 249), who noted: "There are many

methods of drawing pedigrees and describing kinship, butfor my own purposes I still prefer those that I designedmyself." The proposed recommendations of the PSTF are

made as a starting point in the process of adopting uniformpedigree nomenclature. By beginning to use uniform guide-lines for pedigree construction in professional publicationand clinical and research practice, it is possible to reduce the

chances for incorrect interpretation of patient and familymedical and genetic information. It may also improve thequality of patient care provided by genetic professionals,as well as facilitate communication between researchersinvolved with genetic family studies.

AcknowledgmentsThis work was supported by grants from the National Society

of Genetic Counselors; the Washington State Department ofHealth; Maternal/Infant Health and Genetics, the Pacific North-west Regional Genetics Group Project #MCJ-411002-10; andthe University of Washington Division of Medical Genetics andDepartment of Obstetrics and Gynecology. The pedigree symbolsin the figures were formatted using Aldus PageMaker. We aregrateful to the many people who have commented on this projectand for the support from Ann Happ-Boldt, Wendy Uhlmann,and Vickie Venne.

AppendixFictitious Genetic Family History and Pedigree,Using Recommended Pedigree Nomenclature

Clinical ScenarioThe consultand, Mrs. Feene O'Type, age 35 years, and

her 36-year-old husband, Gene O'Type, are referred to youfor genetic counseling regarding advanced maternal age,since Mrs. O'Type is 16 wk into her pregnancy. Mrs.O'Type had one prior pregnancy, an elective termination(TOP) at 18 wk, of a female fetus with trisomy 21.

Mrs. OType and Her Side of the Family* Mrs. O'Type had three prior pregnancies with an ex-

husband, the first a TOP, the second a spontaneous abor-tion (SAB) of a female fetus at 19 wk gestation, and thethird a healthy 10-year-old son who was subsequentlyadopted by her 33-year-old sister, Stacy.

* Stacy had three pregnancies, two SABs (the second amale fetus at 20 wk with a neural tube defect and akaryotype of trisomy 18), and a stillborn female at32 wk.

* Mrs. O'Type has a 31-year-old brother, Sam, who isaffected with cystic fibrosis (CF) and is infertile.

* Her youngest brother, Donald, age 29 years, is healthyand married. By means of gametes from Donald and hiswife, an unrelated surrogate mother has been successfullyimpregnated.

* Mrs. O'Type's father died at age 72 years and her motherat age 70 years, both from "natural causes." Mrs.O'Type's mother had five healthy full sibs, who them-selves had many healthy children.

Mr. OType and His Side of the Family* Mr. O'Type has two siblings, anMZ twin brother, Cary,whose wife is 6 wk pregnant by donor insemination

751

752 Am. J. Hum. Genet. 56:745-752, 1995

* 72 3 24 34 5 6361 my

Is1, 1 130132~~~ 34 3 36, J~~~~+(y 21 3y ,'37 Sl 29 1 1

I45#1 , / 3t5 Sv 10 t EgNAOSA s, InsaD

I I~~~~~~~~~~~~~~~~41

I 2 E k 16ik toy SB 123 5 S 32,1

11

Down Syndrome El- ksryotype_ - Neual tube defect - Cystic fibrodsmutstudy Tuln by: OregrMendd

- C f - - Histois: Gen An Feee OType1 - Cc f~hnds E3 -D ofnoD ake: April 1, 1994- Redren color blihndnes E n dime u stuldy

* minedpe*- Hunuthgon~disse (efficted)

Figure Al Hypothetcal clinical pedigree, using recommended nomenclaure

(donor's history unknown), and a 32-year-old sister,Sterrie.

* Sterrie is married to Proto, her first cousin (Sterrie's fa-ther's sister's son), who has red/green color blindness.She is carrying a pregnancy conceived from Proto'ssperm and ovum from an unknown donor. Sterrie andProto also have an adopted son.

* The family history of Sterrie's mother, who has Hunting-ton disease (HD), is unknown.

* Mr. Gene O'Type's father has a set of twin brothers,zygosity unknown, and another brother and a sister (Pro-to's mother) who are also twins.

Later, You Obtain the Following Information* Feene O'Type's brother, Sam, with CF, has one AF alleleand one allele that cannot be identified.

* Donald carries the AF allele.* Gene O'Type and his twin brother show no clinical signs

of HD, on examination by the neurologist in your clinic.Gene would like DNA testing, but Cary is not interested.

* Sterrie has a normal neurological exam (for symp-toms of HD) in your clinic, but her DNA testingshows she has a CAG expansion of 45 and 18 repeats.

References

Bennett RL, Steinhaus KA, Uhrich SB, O'Sullivan C (1993) Theneed for developing standardized family pedigree nomencla-ture. J Genet Couns 2:261-273

Frankel MS, Teich AH (1993) Ethical and legal issues in pedigreeresearch. Report on a conference sponsored by the AAAS Com-mittee on Scientific Freedom and Responsibility and theAAAS-ABA National Conference of Lawyers and Scientists.American Association for the Advanced of Science, Washing-ton, DC

Galton F (1889) Natural inheritance. MacMillan, LondonGlass R, Motulsky AG, Juengst E, Squires B (1994) Ethicsand the publication of clinical genetics. CBE Views 17(5):70-71

Paris Conference (1971) supplement (1975): standardization inhuman cytogenetics. Birth Defects Original Article Series 11.Vol 9. National Foundation, New York

Resta RG (1993) The crane's foot: the rise of the pedigree inhuman genetics. J Genet Couns 2:235-260

Steinhaus KA, Bennett RL, Uhrich SB, Resta RG, Doyle DL,Markel DS, Vincent VA. Inconsistencies in pedigree nomencla-ture in human genetics publications: a need for standardization.Am J Med Genet (in press)