Establishing a pedigree or drawing a family tree is the key to clinical genetics. The most useful strategy is to start with open questions, such as, Are there any eye diseases in the family? Then proceed further to more targeted questions, as in the case of potential Leber hereditary optic neuropathy (LHON): Did any men on the maternal side of your family lose vision as a young adult?
For patients with a family history, it is best to convert this information into a pedigree diagram—which can be a challenge in some electronic medical records. An initial, rough outline can be drawn on paper and the information can be entered into a simple or more sophisticated pedigree-drawing software program. The standard protocol for pedigree symbols is outlined in Figure 6-1.
Drawing one’s own extended family tree is a useful exercise for the clinician. A basic pedigree should include parents, siblings, and children and should note those affected or unaffected by the disorder of interest. Often, specific inquiry of grandparents, uncles, aunts, and cousins can help clarify the inheritance pattern.
Figure 6-1 Symbols commonly used for pedigree analysis.
(Courtesy of David A. Mackey, MD.)
The interviewer should always ascertain whether brothers and sisters are half siblings or full siblings. This procedure may not only limit the possible patterns of inheritance, but also identify other individuals at risk for the disorder under consideration. Information regarding parentage must be pursued aggressively (but always privately and confidentially). Although incest and nonpaternity are sensitive social issues, their occurrence is not rare. Therefore, when considering rare autosomal recessive diseases, the interviewer must ask specifically about consanguinity. Are the parents cousins? Are there common last names in the families of both parents? Were the parents born in the same area, or do they belong to known ethnic or religious isolates?
Age at death may be useful in specific situations and can be recorded near the appropriate symbols. In the case of a child with ectopia lentis and no family history of similar ocular disease, a clinician may find the identification of a relative who died from a dissecting thoracic aorta in his fourth decade of life very informative, leading to a tentative consideration of Marfan syndrome in the differential diagnosis. In another example, the clinician’s casual observation of atypical tear-shaped congenital hypertrophy of the retinal pigment epithelium (CHRPE) in each eye (Fig 6-2) in a young adult may trigger remembrance that a parent had died at age 50 years from metastatic adenocarcinoma of the colon and a sibling from a brain tumor at age 10 years. Taken together, this information may lead to a diagnosis of Gardner syndrome and referral to a gastroenterologist for further diagnostic evaluation.
Taking a family history does not end with the initial consultation because it may be the first time a patient has heard of the disease. On discussing the new diagnosis with the family, the patient may discover additional family history. Clinicians should encourage patients to talk to their families, and then have patients update their family history at subsequent consultations. For more complicated genetic diseases, a genetic counselor will be able to assist patients with an extensive pedigree.
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;17(5):424–433.
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;56(3):745–752.
Figure 6-2 Atypical congenital hypertrophy of the retinal pigment epithelium (CHRPE) is found in 70%–80% of individuals with familial adenomatous polyposis (FAP). Patients with FAP and other tumors may have Gardner or Turcot syndrome, depending on the type and location of the tumor. Parts A and B demonstrate atypical tear-shaped CHRPE with depigmentation at 1 margin, usually the apex, which points toward the optic nerve. They can be multiple (as shown in part A) or solitary (as shown in part B).
(Reproduced with permission from Bowling B. Kanski’s Clinical Ophthalmology: A Systematic Approach. 8th ed. Oxford: Elsevier Limited; 2016:516.)
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.