Clinical Genetic Skills: Family History & Pedigree Construction

Short version. The first clinical skill taught in genetics is the structured family-history interview, captured as a three-generation pedigree drawn in NSGC-standard notation. The current reference is the 2022 update from Bennett et al. (J Genet Couns 31:1238), building on the 1995 and 2008 versions. Around the symbols sit a series of refinements: ethnicity- and geography-informed history; pregnancy outcomes; consanguinity loops; the diagnostic interview; the dysmorphology examination; and the case vignette as the standard teaching format. Published guidelines such as NICE CG164 and NG101 describe features that warrant further work-up; this page describes those features as they appear in the literature, not as recommendations to the reader.

The structured family-history interview

A genetic family-history interview proceeds in a defined order so that nothing is missed and so that the resulting pedigree is reproducible. Most teaching texts describe a sequence broadly equivalent to the following: introduction and consent for record-keeping; identification of the proband and chief complaint; the proband's own history including age at onset, age at diagnosis, and treatment history; first-degree relatives (parents, siblings, children) with ages, ages at any diagnosis, and ages at death; second-degree relatives (grandparents, aunts, uncles, half-siblings, nieces, nephews); third-degree relatives where information is volunteered or where the pedigree pattern requires it (first cousins); ethnicity and geographic origin of each branch of the family; consanguinity question; pregnancy outcomes including miscarriages, stillbirths, terminations, and infant deaths; adoption and donor-conception status; and any known molecular-genetic test results in relatives.

The NSGC practice resource on genetic family-history collection (Riley et al. 2012, J Genet Couns 21:151) is the standard reference for the order, depth, and language of the questions, and (Hampel et al. 2015, Genet Med 17:70) is the NSGC practice guideline for cancer-specific family-history risk assessment. Each emphasises the same principle: the family history is collected once carefully and updated thereafter, because incomplete or mis-remembered history is the most common source of subsequent misclassification of risk.

The three-generation pedigree convention

A three-generation pedigree is the minimum customary record. The proband's generation is the index; the parents and the parents' siblings are the second generation; the grandparents and their siblings are the third. In practice, four generations is preferred where the information is available, because four generations can resolve patterns of incomplete penetrance, late-onset disease, and reduced expression that three generations cannot. Five and six generations are common in research-pedigree settings, particularly for late-onset adult-disease analysis and for population-isolate studies.

The 2022 Bennett et al. update consolidates the Bennett 1995 and Bennett 2008 references into a single notation reference. The major changes in 2022 are around the more inclusive recording of sex and gender (preserving the long-established square / circle / diamond distinction while introducing a clearer convention for transgender and intersex individuals where the family wishes that to be recorded), and clarifications on adoption, donor conception, surrogacy, and assisted-reproductive-technology lineage. The full notation reference is reproduced on Evagene's NSGC pedigree notation page; three-generation family history covers the depth and width conventions.

Standard pedigree symbols

The symbol set described by Bennett 1995 / 2008 / 2022 is the published consensus. The headline conventions:

Square = male; circle = female; diamond = unknown or unspecified sex.
Filled / shaded shape = affected for the catalogued condition; quadrant fills distinguish multiple conditions.
Diagonal line through a shape = deceased; cause and age at death annotated.
Arrow = proband (the index individual through whom the family came to attention).
Horizontal partner line; double horizontal partner line for consanguinity (with the relationship coefficient annotated).
Vertical descent line; horizontal sibship line; siblings in birth order, eldest on the left.
Triangle for pregnancy / miscarriage / termination, with gestational age annotated.
Brackets around an individual = adopted into the family; square brackets and double dashes describe donor-conceived and adopted-out individuals respectively.
Roman numerals down the left margin for generations; Arabic numerals within a generation for individual identifiers (II-3 = the third individual in the second generation).

For software-assisted drawing, see pedigree drawing tool, pedigree chart, how to draw a pedigree chart, and clinical pedigree drawing. Pedigree symbols reference is the symbol table.

Consanguinity loops

A consanguineous union is one between individuals with one or more common ancestors. In the pedigree the partner line between them is drawn as a double horizontal line, and the loop back to the common ancestor is drawn as a connecting line above. The relationship coefficient (the kinship coefficient F) is annotated; first-cousin matings have F = 1/16, second-cousin matings 1/64. The loop matters because for autosomal recessive disorders the empirical risk of a homozygous-affected child is increased by the parental coefficient of relationship, and pedigrees that conceal a consanguineous loop will misrepresent that risk. See Evagene's consanguinity calculator for the underlying coefficient calculation.

Pregnancy outcomes

Recording pregnancy losses is part of the family history. A triangle marks a non-live-birth pregnancy outcome; a horizontal bar through the triangle indicates termination; gestational age in weeks is annotated below; cause and / or molecular finding (if known) is annotated where the family is comfortable. Recording a pregnancy outcome on the pedigree is sometimes painful for the family; the literature on bereavement-aware family-history collection recommends asking permission first and recording sensitively, particularly in reproductive-genetics settings.

Ethnically and geographically informed family history

Carrier frequencies for several recessive conditions vary substantially by ancestry, reflecting historical bottlenecks and patterns of consanguinity in particular communities. The principal examples taught in genetics curricula:

Ashkenazi Jewish heritage: elevated carrier frequencies for Tay-Sachs disease, Canavan disease, familial dysautonomia, Niemann-Pick disease type A, mucolipidosis type IV, Bloom syndrome, Fanconi anaemia C, Gaucher disease, and several others; in the cancer context, the three founder pathogenic variants in BRCA1 and BRCA2 (BRCA1 c.68_69del [185delAG], BRCA1 c.5266dup [5382insC], BRCA2 c.5946del [6174delT]) are well-recognised.
Mediterranean heritage: elevated carrier frequencies for beta-thalassaemia and (in subsets) glucose-6-phosphate-dehydrogenase deficiency.
South Asian heritage: elevated carrier frequencies for beta-thalassaemia and certain congenital metabolic disorders; consanguinity rates in the literature are higher than the European average.
Sub-Saharan African heritage: elevated carrier frequencies for sickle-cell disease, alpha-thalassaemia, and G6PD deficiency.
Population-specific founder variants are also described in Finnish (Finnish disease heritage), French Canadian (Quebec), Acadian, Old Order Amish and Mennonite, and various other isolated and historically endogamous communities.

Asking about ethnicity and geographic origin is therefore part of a structured family-history interview. The literature (and the 2022 Bennett et al. update) emphasises asking openly and recording without inference; assigning ancestry on the basis of surname or appearance is a recognised source of error.

Red-flag features described in published guidelines

Published guidelines describe specific patterns in a family history as warranting further evaluation. The features below appear in NICE CG164 (familial breast cancer), NICE NG101 (Lynch syndrome), and the NCCN family-history guidelines, among others. They are described here as features the literature flags, not as advice to the reader; clinical decisions in any particular case sit with the clinician responsible for the consultation.

Multiple primary cancers in one individual.
Bilateral disease (e.g., bilateral breast cancer, bilateral retinoblastoma).
Early-onset disease (e.g., breast cancer under age 40, colorectal cancer under age 50).
Clusters of related cancers in a family (the breast-and-ovarian, colorectal-and-endometrial, and gastric-diffuse-and-lobular-breast clusters are characteristic).
Two or more affected first-degree relatives.
An affected male in a typically female-biased disease (e.g., male breast cancer).
Specific syndromic combinations (sebaceous neoplasms with colorectal cancer for Muir-Torre; medullary thyroid with phaeochromocytoma for MEN2; etc.).
Known pathogenic variant in the family.
Ancestry from a population in which a founder variant has been characterised.

The published criteria translate these features into specific thresholds (e.g., the Manchester Score, the BOADICEA model, the Amsterdam II / Bethesda criteria for Lynch). Evagene includes implementations of several of those thresholds for teaching and research use; see hereditary cancer risk assessment, Lynch syndrome risk calculator, BRCAPRO calculator, MMRpro calculator, and the CanRisk file bridge (Evagene exports a CanRisk 2.0 file; clinical-grade BOADICEA computation is run at canrisk.org).

The diagnostic interview

The genetic consultation extends the family-history interview into a full diagnostic interview structured along the same lines as a general medical history, with genetic emphasis:

Chief complaint: the reason the patient or family is being seen. Often includes a referral question (a specific suspicion of a syndrome, a known family variant, a developmental concern).
History of present illness: timeline of the presenting features, age at onset, progression, treatments, response, current status.
Family history: the structured three-generation pedigree as described above.
Developmental history: pregnancy, delivery, neonatal, milestones, schooling, behavioural features. Critical for paediatric-genetics evaluations and dysmorphology referrals.
Past medical and surgical history, medications, and allergies.
Social history: occupation, exposures, tobacco / alcohol / recreational drug use where relevant, partner and reproductive plans.
Review of systems: directed by the differential.

Clinical examination: the dysmorphology assessment

In paediatric and syndromic-genetics consultations, the clinical examination centres on dysmorphology — the systematic description of variations in form (face, hands, feet, skin, hair, ears, nails, palate, palmar creases). Standard reference texts (Hennekam, Krantz & Allanson; Smith's Recognizable Patterns of Human Malformation) define the descriptive vocabulary; the international Elements of Morphology series (Allanson et al. 2009 onwards, Am J Med Genet A) standardised the terms across centres. Photography (with consent) and structured documentation in Human Phenotype Ontology (HPO) terms are increasingly the norm; HPO terms travel through Phenopackets as part of a structured patient summary.

The dysmorphology assessment is taught alongside the cytogenetic / chromosomal context. Karyotype and chromosomal-microarray findings are visualised with ISCN notation on the pedigree, and the karyogram viewer provides a teaching surface for chromosomal aberrations.

The case vignette as a teaching format

Most clinical-genetics teaching uses the case vignette as the primary format: a brief presenting story (chief complaint, age, basic family history) followed by progressive disclosure of additional information, the construction or interpretation of a pedigree, the proposed differential, and the proposed diagnostic and counselling pathway. Case vignettes work because they reproduce the order in which information appears in a real consultation; they teach the trainee to ask the next question rather than simply to recall a fact.

For self-study, the published vignette collections in GeneReviews on the NCBI Bookshelf are an authoritative resource, structured by condition with worked clinical cases, family-history scenarios, and management literature reviewed by the chapter authors. The OMIM entries provide the molecular and phenotypic backbone. Evagene's pedigree chart examples page and the inheritance-pattern-specific calculator pages (autosomal dominant, autosomal recessive, X-linked recessive, mitochondrial, imprinting / UPD, digenic) cover the canonical patterns through worked teaching examples using fictional or anonymised families.

Pedigree drawing in the consultation

In the consultation itself, two practices coexist. Drawing the pedigree on paper in front of the family is widely taught because it slows the conversation to a pace the family can follow, lets the family verify the structure as it grows, and allows the clinician to point at branches as the discussion develops. Drawing the pedigree directly into software during the consultation is increasingly common because the result is preserved as both a structured record and an exchangeable file. Most teaching curricula now expect the trainee to be fluent in both.

Software pedigree drawing is the medium for documentation, exchange, and downstream analysis. Evagene's pedigree drawing tool is a browser-based gesture-driven drawing surface that emits NSGC-compliant SVG, GEDCOM, PED, Phenopackets, and CanRisk files. The tool is positioned as a documentation and teaching surface; clinical-grade computation for risk models is provided either as Evagene's own teaching implementations of the published algorithms (BRCAPRO, MMRpro, Tyrer-Cuzick as an IBIS-style approximation) or via off-platform routes such as the CanRisk file bridge for BOADICEA.

After the family history: where the trainee goes next

Once the pedigree is drawn and the diagnostic interview complete, the clinical-genetic skills strand of training hands off to the diagnostics-and-counselling strand: molecular test choice, variant classification, and the result-disclosure conversation. That is the subject of the companion page diagnostics and counselling. The third strand — the ethical, legal, and social issues of what is being asked of the family, the relatives, and the data — sits at ethics, legal, and social issues.

Boundary statement

This page is a teaching survey of how the family-history interview and pedigree construction skill is taught and described in the literature. It is not a clinical protocol, not a referral guideline, and not advice to any particular case. The Evagene pages it links to are research-, education-, and family-history-documentation tools; none of them is a medical device, none is intended to diagnose, prevent, monitor, predict, treat, or manage disease, and none determines eligibility for screening, testing, referral, or treatment. Where published guidelines describe specific actions, those guidelines are linked; clinical decisions sit with the clinician responsible.

Clinical genetic skills: family-history interview and pedigree construction