SIU School of Medicine

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Department of Internal Medicine

Genetics in Clinical Practice

Rationale

Advances in the understanding of human genetics have occurred rapidly in the past two decades. Some advances are subspecialty, discipline, or disease specific; however, increasingly, genetic principles are becoming applicable to daily clinical practice.

Prerequisites

Prior knowledge, skills, and attitudes acquired during the pre-clerkship experience should include:

  • basic knowledge of human genetics, including structure and function of DNA, basic mechanics of DNA replication, the nature of genetic variation in general and in regard to individual alleles, the effects and types of mutations, and the role of single nucleotide polymorphisms .
  • mechanisms and patterns of inheritance, including autosomal dominant and recessive, x-linked, and mitochondrial
  • the genetics of common or prototypical inherited diseases, such as cystic fibrosis, hemophilia, thalassemia, colon and breast cancer, and Huntington’s Disease
  • commonly used laboratory techniques, including microarray analysis, PCR, Western and Southern Blots, and chromosome analysis
  • basic concepts of drug metabolism, including inheritance and function of CYP system enzymes

Knowledge

Students should be able to define, describe and discuss:

  • the purposes of genetic testing (Diagnostic, Predictive, Carrier identification, Prenatal testing, Preimplantation, Newborn Screening)
  • the value and appropriate use of the family history
  • the inheritance of colon cancer, including FAP and HNPCC and the approach to high risk individuals or families
  • the inheritance of breast cancer, including BRCA1 and BRCA2, and the approach for high risk individuals or families
  • the inheritance of common polygenic conditions, including diabetes mellitus type 2, coronary artery disease, hypertension, hyperlipidemia, and common cancers, and the clinical approach for individuals or families who are at high risk for these conditions
  • the genetic basis for hemochromatosis and how genetic testing is used in diagnosis and treatment
  • the genetic basis for cystic fibrosis, and how genetic testing is used in diagnosis and treatment
  • the genetic basis for alpha-1 antitrypsin deficiency and how genetic testing is used in diagnosis and treatment
  • the genetic basis for hypercoagulable states, and how genetic testing is used in diagnosis and treatment
  • the common ethical, legal, and social issues (ELSI) related to the use of genetic testing in medical practice
  • the best resources for learning more about genetics in clinical practice, especially genetests.org

Skills

Students should demonstrate specific skills, including:

  • History-Taking Skills: Students should be able to obtain, document, and present an age-appropriate medical history, that differentiates among etiologies of disease including:
    • screening family history to identify common inherited conditions, such as colon cancer with attention to HNPCC, breast cancer with attention to BRCA1 and 2, diabetes mellitus type 2, coronary artery disease, hypertension, and hyperlipidemia
    • targeted family history for less common inherited diseases, such as cystic fibrosis, alpha 1 antitrypsin deficiency, hemophilia, hemochromatosis, Huntington’s Disease, Wilson’s Disease, MEN syndromes
    • responses to or side effects from drugs that might be explained by inherited variation in drug metabolism
  • Physical Exam Skills: Students should be able to perform a general physical exam on an adult with attention to identifying physical exam findings common in breast cancer, colon cancer, diabetes, coronary artery disease, hyperlipidemia, cystic fibrosis, alpha 1 antitrypsin deficiency, hemophilia, hemochromatosis, Huntington’s disease, Wilson’s disease and MEN syndromes
  • Differential Diagnosis: Students should be able to generate a prioritized differential diagnosis recognizing specific history and physical exam findings that suggest a specific inheritance pattern or genetically related condition, including:
    • colon cancer—HNPCC, FAP, or polygenic inheritance
    • breast cancer—BRCA1, BRCA2, or polygenic inheritance
    • MEN syndromes
    • iron overload and hemochromatosis
    • cystic fibrosis
    • alpha 1 antitrypsin deficiency
    • hypercoagulable states, including Protein C and S deficiencies, Factor V Leiden, and Prothrombin gene mutations
    • hemophilia
    • altered responses to selected drugs

  • Laboratory Interpretation: Students should be able to define the indications for and interpret (with consultation) the significance of the results of genetic tests for the following target conditions :
    • BRCA 1 and 2 in breast and ovarian cancer
    • Ret-oncogene in medullary carcinoma of the thyroid
    • MLH1, MSH2, and microsatellite instability testing in colon cancer
    • C282Y testing in hemochromatosis
    • Cystic fibrosis genetic screens
    • Factor V Leiden and prothrombin gene mutations
    • CYP2D6, CYP2C9, and CYP2C19 testing for drug metabolism

  • Communication Skills: Students should be able to:
    • communicate the diagnosis, treatment plan, and subsequent follow-up to patients and their families
    • discuss general risks and benefits of genetic testing for at risk or affected patients or family members, for diagnosis, for predictive purposes, or for carrier detection

  • Management Skills: Students should be able to develop an appropriate evaluation and treatment plan for patients that includes:
    • appropriate consultation from a geneticist or genetic counselor for predictive genetic testing
    • identifying conditions for which family history information will alter screening, diagnosis, or treatment.
    • a cost-effective approach based on the differential diagnosis
    • patient preferences

Attitudes and Professional Behaviors

Students should be able to:

  • recognize the importance of patient preferences when selecting among diagnostic and therapeutic options related to genetic testing
  • respond appropriately to patients or family members who decline genetic testing
  • demonstrate ongoing commitment to self-directed learning regarding genetics in clinical practice
  • appreciate the impact genetic testing may have on a patient or family
  • recognize important ELSI (Ethical, Legal and Social Issues) related to genetic conditions and testing in medical practice, including confidentiality, informed consent and inappropriate use of genetic test results,
  • recognize the importance of and demonstrate a commitment to the utilization of other healthcare professions in genetic testing and counseling of patients and families.

Resources

  • Clerkship Seminar, “Genetics in Clinical Practice,” D. Steward, MD, MPH
  • www.genetests.org
  • www.genome.gov
  • Thompson & Thompson Genetics in Medicine, 6th edition, 2004; by Nussbaum, McInnes, and Willard. Saunders Publishing,
  • Case Studies in Genes and Disease, a Primer for Clinicians, 2004. by Bryan Bergeron, M.D. Published by American College of Physicians

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