The Practical Guide to the Genetic Family History

Robin L. Bennett

• Editorial: Wiley-Blackwell
• Año: 2011
• ISBN:
  9781118209813
• Edición: 2
• Categoría: Medicine
• Categoría: Genetics in Medicine

HELPS YOU DEVELOP AND ASSESS PEDIGREES TO MAKE DIAGNOSES, EVALUATE RISK, AND COUNSEL PATIENTS

The Second Edition of The Practical Guide to the Genetic Family History not only shows how to take a medical-family history and record a pedigree, but also explains why each bit of information gathered is important. It provides essential support in diagnosing conditions with a genetic component. Moreover, it aids in recommending genetic testing, referring patients for genetic counseling, determining patterns of inheritance, calculating risk of disease, making decisions for medical management and surveillance, and informing and educating patients. Based on the author's twenty-five years as a genetic counselor, the book also helps readers deal with the psychological, social, cultural, and ethical problems that arise in gathering a medical-family history and sharing findings with patients.

Featuring a new Foreword by Arno Motulsky, widely recognized as the founder of medical genetics, and completely updated to reflect the most recent findings in genetic medicine, this Second Edition presents the latest information and methods for preparing and assessing a pedigree, including:

• Value and utility of a thorough medical-family history
• Directed questions to ask when developing a medical-family history for specific disease conditions
• Use of pedigrees to identify individuals with an increased susceptibility to cancer
• Verification of family medical information
• Special considerations when adoptions or gamete donors are involved
• Ethical issues that may arise in recording a pedigree

Throughout the book, clinical examples based on hypothetical families illustrate key concepts, helping readers understand how real issues present themselves and how they can be resolved.

This book will enable all healthcare providers, including physicians, nurses, medical social workers, and physician assistants, as well as genetic counselors, to take full advantage of the pedigree as a primary tool for making a genetic risk assessment and providing counseling for patients and their families.

Chapter 1

The Language of the Pedigree

Pedigrees are a challenge. With their intricate patterns of geometric symbols, pedigrees are like biological crossword puzzles which dare the clever and creative geneticists to solve them for clues about inheritance, family dynamics, or the localization of a gene.

—Robert G. Resta (1995)

1.1 WHY TAKE TIME TO RECORD A GENETIC FAMILY HISTORY

The field of human genetics has revolutionized the practice of medicine. The cyberspace bible of human genetics—Victor McKusick’s Online Mendelian Inheritance in Man (better known as OMIM)—lists more than 10,000 hereditary traits and conditions. Identification of genetic mutations through the International Human Genome Project makes genetic testing for most of these conditions a reality. Genetic susceptibility mutations are being identified as part of the causal nexus for complex medical conditions such as cancer, diabetes, heart disease, Alzheimer disease, and mental illness. Human genetics is no longer just a topic for obscure medical journals. Headlines heralding genetic advances are splashed across the fronts of newspapers and popular magazines. The gripping stories of people making heart-wrenching decisions about genetic testing and diagnosis increase the Nielsen ratings of Oprah Winfrey-style talk shows and hospital-based television medical dramas. Patients come to you wanting to know if they need to worry about a genetic disease during their pregnancies, in their children, or in relation to their own healthcare.

How can you as a clinician identify individuals at risk for genetic disorders? Often, the first step is to take a genetic family history, recorded in the shorthand form of a pedigree. A pedigree, commonly referred to as a family tree, is a graphic representation of a medical-family history using symbols. A concise pedigree provides both critical medical data and biological relationship information at a glance. In many circumstances, the pedigree is just as important for providing medical services to the patient as any laboratory test. In fact, the pedigree has been described as the “first genetic test.” This is both a historical reference to the fact that pedigrees have been used in medicine for over 100 years and also that a pedigree is the first step for genetic evaluation. The pedigree is truly the symbolic language of clinical genetic services and of human genetic research.

Genetic diseases affect all organ systems. Therefore health professionals from all specialties need to learn to think genetic. You need not be a “clever and creative geneticist” (Resta, 1995) to take a genetic family history. The purpose of this book is to provide you with practical screening tools to make an assessment as to whether your client might benefit from more extensive genetic evaluation and/or testing. My goal is provide you with not just the family history questions to ask but the logic behind this questioning. Health professionals working with clients in family practice, internal medicine, pediatrics, neurology, oncology, and obstetrics will find these screening tools particularly useful.

A focus of this book is genetic screening questions for clinical specialists by disease system (see Chapter 4). The emphasis in Chapter 5 and Appendix 3 is family history tools for identifying individuals with an inherited susceptibility to cancer. Researchers in human genetics will find useful information on how to obtain family history information, as well as ethical issues to consider in family studies and the publication of pedigrees (see Chapter 10). For the benefit of professionals involved in adoption, in Chapter 7 I discuss the unique issues surrounding a genetic family history and adoption. In Chapter 8 I delve into some of the challenging aspects of family history in the context of assisted reproductive technologies and the use of donor gametes. Appendix 4 is a medical-family history questionnaire that could be used for a child being placed for adoption, or for health information for an egg or sperm donor, or surrogate mother.

1.2 WHAT DO CRANES HAVE TO DO WITH ANYTHING?

The word pedigree comes from the French pie de grue, or “crane’s foot.” The term first appeared in the English language in the 15th century. It described the curved lines resembling a bird’s claws that were used to connect an individual with his or her offspring (Resta, 1993). Such vestiges of a bird’s talons are obvious in the example of the sippschaftstafel drawn by Ernst Rüdin shown in Figure 1.1. The sippschaftstafel was a form of depicting family ancestry used by German eugenicists in the early 20th century (Mazumdar, 1992; Resta, 1993).

Figure 1.1 A sippschaftstafel drawn by German eugenicist Ernst R üdin in 1910. Note the proband (circle with irregular edge) is placed in the center of the pedigree and the maternal and paternal lineages radiate from curved lines drawn to the proband). Here the proband is shown being crushed by the weight of her dysgenic ancestry. (Reprinted with permission from Mazumdar, 1992; and Resta, 1993.)

A pedigree is of limited value if the symbols and abbreviations cannot be easily interpreted. Historically, many different pedigree styles have been used in the published literature and in patient medical records (Bennett et al., 1993; Resta, 1993; Steinhaus et al., 1995). In fact, genetics professionals probably use as many pedigree dialects as there are forms of the human language. As Francis Galton (an early geneticist and cousin to Charles Darwin) observed, “There are many methods of drawing pedigrees and describing kinship, but for my own purposes I still prefer those that I designed myself” (Galton, 1889). By using uniform symbols, it is possible to reduce the chances for incorrect interpretation of patient, family, medical, and genetic information.

Through a peer-reviewed process, the Pedigree Standardization Task Force (PSTF) of the National Society of Genetic Counselors (NSGC) developed standardized nomenclature for symbolizing pedigrees (Bennett et al., 1995). These have become an international standard, and the symbol set has required little revision since the original publication (Bennett et al., 2008). All pedigree symbols in this book conform to these standards.

1.3 THE PEDIGREE IS A COST-EFFECTIVE TOOL FOR GENETIC DIAGNOSIS AND RISK ASSESSMENT FOR MANY DISEASES

“But who has time to take a family pedigree?” is a common lament from the busy practitioner. Most clinicians record some information about a patient’s family illnesses in textual form. This can be just as time-consuming as recording a pedigree, and the text may be both lengthier and less informative than a pedigree. For example, consider this excerpt from a medical record:

Linda’s grandmother and two aunts died of breast cancer.

Did the cancer occur in Linda’s maternal or paternal grandmother? Are the aunts the sisters of Linda’s mother or her father? Did they have breast cancer before or after onset of menopause? The exact relationship of these affected relatives to Linda, their ages at diagnosis, and if the breast cancer was unilateral or bilateral can make a critical difference in your clinical assessment of Linda’s lifetime risk of developing breast cancer. Instead, using the associative icons of a pedigree, the relevant family and medical information can be recorded quickly and precisely, in an easily interpretable format. A family pedigree has many functions; it is a tool for:

• Making a medical diagnosis.
• Deciding on testing strategies.
• Establishing the pattern of inheritance.
• Identifying at-risk relatives.
• Calculating disease risks.
• Determining reproductive options.
• Distinguishing genetic from other risk factors.
• Making decisions on medical management and surveillance.
• Developing patient rapport.
• Educating the patient.
• Exploring the patient’s understanding.

Each of these benefits of collecting a pedigree will be explored further in this chapter.

1.4 JUST DO IT ©

The popular advertisement “Just Do It” from the sports company Nike (Center for Applied Research, 2008) is applicable to the attitude that should be assumed by most health professionals regarding documenting a patient’s medical-family history. Taking a directed genetic history is a primary step in the evaluation of many medical disorders. Barton Childs (1982) predicts that “to fail to take a good family history is bad medicine and someday will be criminal negligence.” Notation of a genetic family history is likely to become an essential component of a patient’s electronic medical record (Bennett et al., 2008). The family history that is placed in a newborn’s electronic medical record may travel through the health system during that person’s life, with the pedigree undergoing various iterations as the individual faces age-related health risks and changing familial risks as diseases develop in relatives.

The ability to elicit a comprehensive medical family history including a family pedigree, is stated as a fundamental skill for all health professionals, according to the National Coalition for Health Provider Education in Genetics (NCHPEG, 2007). Peter Schwartz of Yale University School of Medicine states that for early screening and detection of gynecological malignancies, “Family history is crucial, and it’s not a superficial history. You have to go into depth” (Stone, 1998). Both the American College of Obstetrics and Gynecology (ACOG) and the American Society of Clinical Oncologists (ASCO) have had long-standing statements recording the importance of family history in obstetrics evaluations and cancer risk assessment, respectively (ACOG, 1987; ASCO, 1997).

Using a pedigree to symbolize a patient’s medical and genetic history is no more time-consuming that dictating a detailed summary for the medical chart. A pedigree is a way to compress pages and pages of medical information on to an 8¹/₂ by 11-inch piece of paper, or the screen of an electronic medical record. I always keep the patient’s pedigree in the front of his or her medical file. This saves me time at subsequent visits because most of the critical information I need is readily accessible and succinctly summarized in one page. The pedigree gives me an immediate image...