Genetic history, pedigree construction and inheritance patterns

A registrar is asked to assess a three-year-old with global developmental delay and is told, almost as an afterthought, that "there is something in the family." The fellowship task is not to reach for an exome first — it is to sit down and draw the pedigree. Three generations, both parental lines, the consanguinity double-line if it applies, the uncles who died in infancy, the maternal male cousin in a wheelchair, the ethnicity, the miscarriages. From that single sheet of paper the inheritance pattern declares itself, the investigation narrows, and the recurrence risk becomes a number the family can use. The pedigree is the foundation of all of clinical genetics, and it is the skill most often skipped. [1] [2]

Overview & Definition

A genetic family history is the structured collection of information about disease in a child's relatives, and a pedigree is its graphical representation, drawn in standardised symbols across at least three generations. The pedigree is not a decoration for the notes — it is a clinical investigation that reorganises a vague sense that "something runs in the family" into a recognisable inheritance pattern, a recurrence risk, and a rational plan for testing and counselling. The National Society of Genetic Counselors standardised pedigree nomenclature precisely so that any clinician, anywhere, could read the same family story from the same symbols. [1] [2]

The reason the pedigree is the foundation of clinical genetics is that the inheritance pattern governs everything that follows — which test to order, what the result means, what the risk is to siblings and future children, and what reproductive options exist. An autosomal dominant family is offered a different conversation from an autosomal recessive family, and both differ from an X-linked family in which the carrier sisters face their own reproductive decisions. Recognising the pattern early prevents the common error of ordering the wrong test, or the right test on the wrong relative. [1] [6]

Inheritance patterns are conventionally grouped into Mendelian (autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive), non-Mendelian (mitochondrial or maternal, genomic imprinting and parent-of-origin effects, anticipation from trinucleotide-repeat expansion, mosaicism), and multifactorial or polygenic inheritance, with chromosomal disorders forming a parallel category. The same paediatric presentation — developmental delay, a birth defect, a metabolic decompensation — can arise from any of these, and the pedigree is the instrument that distinguishes them. [2] [7]

References10Show ledgerHide ledger

1. [1]Bennett RL, French KS, Resta RG, Doyle DL. Standardized human pedigree nomenclature: update and assessment of the recommendations of the National Society of Genetic Counselors. J Genet Couns, 2008.PMID 18792771
2. [2]Bennett RL, Steinhaus KA, Uhrich SB, et al. Recommendations for standardized human pedigree nomenclature. Pedigree Standardization Task Force of the National Society of Genetic Counselors. Am J Hum Genet, 1995.PMID 7887430
3. [3]Bittles AH, Black ML. Evolution in health and medicine Sackler colloquium: Consanguinity, human evolution, and complex diseases. Proc Natl Acad Sci U S A, 2010.PMID 19805052
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6. [6]Gelb BD. 2024 ASHG presidential address: Incomplete penetrance and variable expressivity: Old concepts, new urgency. Am J Hum Genet, 2025.PMID 40054435
7. [7]Butler MG. Clinical Presentation, Genetics, and Laboratory Testing with Integrated Genetic Analysis of Molecular Mechanisms in Prader-Willi and Angelman Syndromes: A Review. Int J Mol Sci, 2026.PMID 41683698
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9. [9]Lecoquierre F, Drouot N, Coutant S, et al. Parental germline mosaicism in genome-wide phased de novo variants: Recurrence risk assessment. PLoS Genet, 2025.PMID 40163539
10. [10]Verebi C, Gravrand V, Bienvenu T, et al. A retrospective cohort study and review of the literature about germline mosaicism in Duchenne muscular dystrophy. J Genet Couns, 2025.PMID 38895972