DANIEL J. WATTENDORF, MAJ, MC, USAF E DONALD W. HADLEY, M.S.
I'm a family doctor.2005;72(3):441-448
See editorial on page 386.
Author Disclosure: Nothing to disclose.
Collecting family history can range from simply asking patients if family members have the same illness, to graphing complex medical and psychosocial relationships as part of a family genogram. The three-generation pedigree provides a visual representation of disease within a family and is the most efficient way to assess hereditary influences on disease. Two recent events have made the assessment of family history more important than ever: the completion of the Human Genome Project, with the consequent identification of the hereditary causes of many diseases, and the establishment of national clinical practice guidelines based on systematic reviews of preventive interventions. Family history is useful for stratifying a patient's risk for rare single-gene diseases and more common diseases with multiple genetic and environmental contributors. Major organizations have advocated the use of standardized symbols in family trees to identify inherited contributions to disease.
A three-generation pedigree was used for diagnostic consideration or risk assessment of rare or single-gene chromosomal disorders. However, the usefulness of family history in assessing the risk of common diseases is increasingly recognized.1–3The most common diseases result from a combination of environmental factors and variations in multiple genes. Inherited variations within these genes confer individual risks that can vary widely from population averages. Assessing family history is helpful in identifying increased risks for diseases with modifiable risk factors or preventable exposures. Clinical Preventive Measures for Asymptomatic Patients Approved by the US Preventive Services Task Force include consideration of relevant family history (table 14–13🇧🇷 Evaluation of family history can also help identify relatively rare disorders that may not be considered in a differential diagnosis (Table 2🇧🇷 Alternatively, when a relatively common disease is caused by an inherited mutation in a single gene, investigation of family history can lead to earlier diagnosis and more aggressive treatment.Tisch 3).
|ONE||Aspirin for primary prevention of cardiovascular events4||Discuss aspirin chemoprevention with adults at increased risk of coronary artery disease.||Risk assessment should include questions about age, sex, diabetes, high total cholesterol, low high-density lipoprotein cholesterol, high blood pressure, family history, and smoking.|
|ONE||colon cancer screening5||Screen men and women age 50 and older for colorectal cancer.||For those most at risk (for example, a first-degree relative diagnosed before age 60), it makes sense to start screening earlier.|
|Expert guidelines exist for screening very high-risk patients, including those with a history suggestive of familial polyposis or hereditary nonpolyposis colorectal cancer.|
|B||Behavioral counseling in primary care to promote healthy eating6||Counsel adult patients with hyperlipidemia and other known risk factors for chronic cardiovascular and nutritional disorders.||—|
|B||Breast cancer chemoprevention7||Discuss chemoprevention with women at high risk of breast cancer and low risk of chemoprevention side effects.||Advanced age, a family history of breast cancer, and a history of atypical hyperplasia on breast biopsy are the most important risk factors for breast cancer.|
|B||Abdominal aortic aneurysm screening8||Perform a single ultrasound on men aged 65 to 75 who have ever smoked.||Major risk factors include age (65 years or older), male gender, and a history of smoking (at least 100 cigarettes in a person's lifetime). A family history of a first-degree abdominal aortic aneurysm that requires surgical repair also increases the risk in men.|
|B||breast cancer screening9||For women age 40 and older, get a screening mammogram with or without a clinical breast exam every one to two years.||Women at higher risk of breast cancer (eg, women with a family history of breast cancer in a mother or sister, a previous breast biopsy with atypical hyperplasia, first birth after age 30) are more likely to benefit regular mammograms than low-risk women.|
|B||Screening for lipid disorders in adults10||Evaluate men aged 20 to 35 years and women aged 20 to 45 years with diabetes, family history of cardiovascular disease before age 50 for male relatives or before age 60 for female relatives, or family history that indicates familial hyperlipidemia.||—|
|D||Pancreatic cancer screening11||Do not routinely screen pancreatic cancer by abdominal palpation, ultrasonography, or serological markers in asymptomatic adults.||People with hereditary pancreatitis may have a higher risk of developing pancreatic cancer during their lifetime.|
|you||prostate cancer screening12||There is insufficient evidence to recommend for or against routine prostate cancer screening with prostate-specific antigen testing or digital rectal examination.||Men over age 45 who are at risk (eg, African American men, men with a family history of prostate cancer in first-degree relatives) are more likely to benefit from screening.|
|you||Hearing screening for newborns13||There is insufficient evidence to recommend or against routine screening for hearing loss in newborns during the postpartum hospitalization.||Screening throughput and proportion of true positives are significantly higher when screening is directed toward high-risk infants (eg, family history of infant sensorineural hearing loss, congenital infections, and craniofacial abnormalities).|
|primary symptom||family history||illness||generation|
|fatigue or arthralgia||diabetes or cirrhosis||hereditary hemochromatosis||HFE|
|non-febrile seizure||Seizures, developmental delay, mental retardation, tumors||tuberous sclerosis||TS1, TS2|
|recurrent UTI or hematuria||Hypertension, nephrolithiasis, cerebral aneurysm or renal failure||autosomal dominant PKD||ADPKD1, ADPKD2|
|difficulty breathing||Nosebleeds, telangiectasias||hereditary hemorrhagic telangiectasia||GER, ACVRL1|
|difficulty breathing||Heart failure (cor pulmonale)||idiopathic pulmonary hypertension||BMPR2|
|Syncope||syncope, sudden death||long QT syndrome||Several|
|To diagnose||family history||disease etiology||generation|
|TVT||DVT, pulmonary embolism||hereditary thrombophilia||Several; F5|
|Most common: activated protein resistance factor V Leiden|
|Glaucoma (primary open storage)||Glaucoma||hereditary glaucoma||MYOK|
Prevention efforts are enhanced by family discussions that shed light on lifestyles or behaviors in the family that have adverse health outcomes. Prevention is also achieved by identifying patients at higher risk than the population average due to shared hereditary factors associated with the disease. In some cases, standard screening can be replaced with targeted genetic testing and a shift in clinical intervention to those at high risk of disease, eg B. in people with a strong family history of cancer.
Family History Office Collection
Doctors can use several approaches to gather family information and create a family tree. The more traditional approach is a physician-led patient or family interview. Nurses, medical assistants, and other trained physicians can also complete this process. This approach usually takes 15 to 30 minutes. Alternatively, patients can be given questionnaires about their family history before visiting a doctor. This method still requires a doctor to review the information and create a pedigree.
Unfortunately, a health visit does not allow that time to be devoted to taking a family history.14In fact, the average office visit lasts 16 minutes, and family history conversations last less than three minutes.quince,sixteenMany physicians compensate for this time constraint by collecting fragmented family history information over multiple visits. Checklists can be used to speed up data collection, but the usefulness of this approach may be limited by patient memory. Checklists should also not distinguish which family members are affected or how close they are to the patient. In addition, unknown family medical information, the patient's focus on an acute problem, and fear of discrimination can make it difficult to collect a complete and accurate family history.
Collection of family history of patients
With guidance, patients can create their own family trees, which must be reviewed by the physician to ensure accuracy. The American Medical Association has developed a pocket guide that provides instructions and examples for patients to create a pedigree. It is available online athttp://www.ama-assn.org/ama/pub/category/2380.html.
A print and web-based tool developed as part of the US Surgeon General's Family History Initiative was developed17is available online athttp://www.hhs.gov/historia familiar🇧🇷 This tool, available in both English and Spanish, guides the collection of family history, which is then translated into a standardized, printable three-generation family tree. Specific questions focus on six adult diseases: heart disease; Diabetes; running; and breast, ovarian, and colon cancer. These diseases are highlighted because they are common and require a change in clinical evaluation or intervention based on family history. Families are encouraged to obtain specific information directly from family members, their physicians and medical records.
Whether the family history was obtained in the physician's office or at the patient's home, the assessment should be performed at the initial patient assessment and updated regularly to identify newly diagnosed medical or developmental conditions in the family. Clinicians should begin by recording the current age and age at onset of symptoms or diagnosis for the patient and first-, second-, and third-degree relatives on both sides of the family. The age and cause of death of deceased relatives should also be recorded. The accuracy of the information generally decreases as the degree of relatedness decreases. Therefore, clinicians need to know that the information is coming from a medical source and not from family history.
The most useful family history includes information about the medical, developmental, and pregnancy outcomes of first-, second-, and third-degree relatives.18The degree of relatedness indicates the percentage of common genes (Table 4🇧🇷 For example, a patient's half-siblings and uncles inherit an equal proportion (25%) of genes identical to the patient's. Standard symbols and diagrams allow quick assignment of diseases to specific family branches (illustration 119🇧🇷 If two relatives on the same side of the family have cancer (one with endometrial cancer and one with colon cancer), the suspicion of hereditary nonpolyposis colon cancer (an inherited form of colon cancer) is raised more than if one relative of the father's side came from the family and the other from the mother's side.
|First degree relatives (50% common genes)||Second degree relative (25% common genes)||Third-degree relative (12.5% of common genes)|
|Kinder||aunts and uncles||cousins|
|nieces and nephews|
Medical information is often not known due to generational, cultural or health literacy issues. For example, older relatives mistakenly believe that discussing a cancer diagnosis is pointless because there has been no effective treatment in the past. A couple planning to have children may not realize the importance of asking about previous miscarriages in the family, and family members may not willingly share this emotionally sensitive information. Conditions thought to occur sporadically may actually be inherited. For example, a family history of several relatives with Down syndrome suggests an inherited translocation, not sporadic nondisjunction. A woman may not realize that her paternal grandmother's and aunt's breast cancer diagnoses pose the same risk to her as if they were maternal relatives. Therefore, an encouraging collection of health information for three generations of relatives is warranted.
Consanguinity, the shared relationship of a common ancestor, is common in many cultures and should be considered when evaluating a patient with unusual symptoms or symptoms indicative of a rare disease. Individuals from cultures where intermarriage is common share a greater proportion of genes. In Iraq, for example, 29.2% of marriages are between first cousins and 57% of marriages have some degree of consanguinity.20An autosomal recessive disorder is more likely to run in a consanguineous family because a person is more likely to have two copies of the same mutation in a gene.21Recurrence of common complex disorders may also increase in children born to consanguineous parents due to a higher proportion of shared genes.
Physicians must identify patients' ancestors and, if known, their grandparents' countries of origin. A single gene can have genetic variations, whose frequencies differ depending on the origin of the ancestors. A low mean corpuscular volume and normal iron levels in a patient without chronic disease indicate a diagnosis of trait thalassemia. If a patient and their partner with these findings are confident that their ancestors were from Africa, the chance of having a clinically affected child is very small. But if the patient or partner is of Southeast Asian descent, there is an increased risk of H-thalassemia or even fatal hydrops in their child. Many diseases are more common in certain ancestral groups. For example, people of Ashkenazi Jewish or Muslim Arab origin share a one in four chance of having a defective gene for familial Mediterranean fever.22In these patients, it is important to be aware of the risk of disease, as early diagnosis prevents prolonged detection of other diseases and allows for effective treatment.
The memory of miscarriages, stillbirths, illnesses and deaths in the family can provoke strong emotional reactions in patients. Feelings of guilt and disapproval are not uncommon in families where several members are affected by the same illness. Viewing the family history in pictorial form can shed light on risks for a patient that have not been previously assessed. It may be helpful to establish a relationship with a geneticist or genetic counselor, although geneticists are not widely available. Additional time in the clinic and support from mental health professionals may be needed.
Family members who are at significant risk of disease and for whom early intervention can improve outcomes can sometimes be identified. The patient should be encouraged to inform these family members of their risk and refer them to a physician. In such cases, the physician's duty to directly alert other family members is unclear.23There have been successful malpractice suits against physicians for failing to warn patients that their relatives were at increased risk for colon and breast cancer.24
The physician's precise duty in these cases often goes unexamined, especially given the limitations of the Health Insurance Portability and Accountability Act, and is subject to interpretation by individual state courts. Therefore, disclosure to other family members must be carefully considered with respect to privacy and balanced with the obligation to give notice.
When family history suggests a genetic condition
In some patients, family history may be significant enough (eg, multiple affected relatives with early-onset disease) to warrant consideration of genetic testing for an identified or suspected mutation in a single gene. If the analyzed gene is part of a complex disease, the mutation found provides susceptibility or predictive information, but not confirmatory information. The level of risk attributed to variations or mutations in a single gene can range from a modest contribution in complex diseases to almost 100% certainty. For example, a variation inAPCGene found in Ashkenazi Jewish population confers modest risk of colon cancer.25Other mutations in the same gene cause familial adenomatous polyposis with a lifetime colorectal cancer risk of nearly 100 percent.
Sensitivity or predictive testing for familial cancers can significantly reduce morbidity or mortality through changes in disease management. Alternative screening tests with less specificity but greater sensitivity (eg, MRI for breast cancer detection) may be sought, and chemoprophylaxis (eg, tamoxifen [Nolvadex] for breast cancer prevention) may be offered. breast cancer). Aggressive screening and surgical prophylaxis (eg, colonoscopy to detect and remove precancerous lesions in patients with hereditary nonpolyposis colorectal cancer) may be instituted. As a preventive measure, early surgical intervention may be recommended (for example, for relatives of a patient with a genetic mutation).MEN2AGene that inherits a mutation inWITHDRAWNand are virtually certain to develop medullary thyroid carcinoma) or offered (eg.BRCA1/2Mutation). Predictive tests can also be started for non-cancerous conditions. In an adult with asthma that does not improve with bronchodilators, the risk of α-1 antitrypsin deficiency increases if there is a family history of emphysema or bronchiectasis. If lung function tests show that the airway obstruction is incompletely reversible, the patient is a candidate for genetic testing.26
Family history can also guide the diagnosis, even when DNA-based genetic testing for an inherited disorder is not available. In a child who has a syncopal episode, a family history of syncope suggests long QT syndrome.27In an adult with fatigue or arthralgia, a family history of diabetes and cirrhosis should prompt measurement of transferrin saturation and consideration of hereditary hemochromatosis.28
New guidelines that incorporate genomic principles into the assessment of family history enhance the usefulness of this powerful clinical tool. Taking a traditional "directed" family history may be necessary in emergencies or when time is limited, but it should not replace the three-generation pedigree chart for each patient.
Glossary of Genomics
Consanguinity:A genetic relationship between people who descend from a common ancestor. The blood relationship increases the chance of inheriting identical versions of a given gene.
Tutor:A person who seeks genetic counseling to obtain information about a disease or condition in the family.
Predictive genetic tests:Determine the genetic variation in an asymptomatic individual to determine whether the probability of a given disease or condition is greater than the population mean.
test:The person in a family affected by a disease or condition that raises suspicion that other family members may be more susceptible to the same disease or condition.