The presence or absence of any effect of a gene is called penetrance. If a gene generates any evidence of phenotypic features, no matter how minimal, it is termed penetrant. If it is not expressed at any level of detection, it is termed nonpenetrant.
In families with an autosomal dominant mutant gene that has 100% penetrance of the phenotype, an average of 50% of the offspring will inherit the gene and show evidence of the disease.
Although penetrance has an exact statistical definition, its clinical ascertainment is affected by diagnostic awareness and the methods of physical examination. For example, many mild cases of Marfan syndrome would be missed without careful biomicroscopy of the fully dilated pupil and echocardiography of the heart valves and great vessels. Similarly, if the criteria for identification of the retinoblastoma gene include indirect ophthalmoscopy and scleral depression, some “nonpenetrant” parents or siblings in families with “dominantly inherited” retinoblastoma may be found to have a spontaneously involuted tumor, which clearly identifies them as bearers of the gene. In another example, some family members who have a gene for Best macular dystrophy will be identified not by clinical ophthalmoscopic examination but only by electro-oculographic testing. Therefore, in examining a potential bearer of a gene, the examiner must carefully search for any manifestations of the gene’s effects in all susceptible tissues before dismissing someone as from a “skipped generation.”
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.