HL7 Clinical Genomics Work Group
The Family History Standard – Implementation Guide
(US Realm)
DRAFT - August 14, 2012
Pedigree R1 Co-Editors:
Dr. Amnon Shabo (Shvo)[1]
Dr. Kevin S. Hughes[2]
US Realm IG Co-Editors:
Dr. Amnon Shabo (Shvo)
Mollie H. Ullman-Cullere
Yan Heras
[please add your name if you contribute to this document]
© 2011 Health Level Seven, Inc.
Ann Arbor, MI
All rights reserved.
Table of Contents
1 Introduction 6
2 storyboards 7
2.1 Cancer - BRCA 7
2.1.1 Storyboard Presentation 8
2.2 Sample Pedigrees 10
2.2.1 Annie Proband: 10
2.2.2 Indiviual with PKU: 11
2.2.3 Indiviual with Dominantly Inherited Hypertrophic Cardiomyopathy: 12
2.2.4 Indiviual with an X-linked Dilated Cardiomyopathy: 13
3 The Family history model 15
3.1 Model Walkthrough 15
3.1.1 Entry Point - FamilyHistory 15
3.1.2 Patient & Person 15
3.1.3 Clinical 16
3.1.4 Informant 16
3.1.5 PedigreeAnalysisResults 16
3.1.6 Relative 18
3.1.7 ? 18
3.1.8 subjectOf2 Shadow 19
3.1.9 Person and Relative 19
3.1.10 Relative’s Mother and Father Identifiers 20
4 vocabularies 22
4.1 Family Relationships 22
4.2 Genetic Data within a Pedigree/Family History 22
4.3 Age Attributes 23
4.3.1 Age at Death 23
4.3.2 Age of Onset of Disease 23
4.3.3 Age of Living Subject 23
4.4 Race 24
4.5 Ethnicity 24
4.6 Relative 24
5 Exchange of a person’s family health history 26
6 appendix a: The family history (Pedigree) model 29
7 appendix B: hierarchical vs. flat representation 31
8 appendix C: The Geneticlocus r-mim 33
9 appendix D: xml schema and samples 34
10 appendix E: HITSP specifications on personalized healthcare 35
Table of Figures
Figure 1: Common Visualization of a Family Health History: Breast Ovarian Cancer Syndrome 11
Figure 2: Common Visualization of a Family Health History: PKU 12
Figure 3: Common Visualization of a Family Health HIstory: Dominantly Inherited Hypertrophic Cardiomyopathy 13
Figure 4: Common Visualization of a Family Health History: X-linked Dilated Cardiomyopathy 14
Figure 5: The Recursive Association of Person and Relative Which Enables a Hierarchical Representation of a Pedigree to Any Depth Needed 21
Figure 6: The Family History (Pedigree) Model R-MIM 30
Figure 7: The GeneticLocus R-MIM 33
Figure 8: Construct Personal and Family Health History & Pedigree 36
Figure 9: Scenario 1: Clinical Assessment Component Data Flow Diagram 37
Table of Tables
Table 1: Outline for Family History of a Cancer Patient 7
Table 2: Age at Death 23
Table 3: Age of Onset of Disease 23
Table 4: Age of Living Object 23
Table 5: Race Value Set (excerpt) 24
Table 6: Ethnicity Value Set 24
Table 7: Personal Relationship Role Type Value Set (excerpt) 24
1 Introduction
A number of family history applications were in use by health care professionals (e.g., HughesRiskApps, CAGENE, Progeny) as well as by patients (e.g., the US Surgeon General’s Family History Program). Each application had its own proprietary data format for pedigree drawing and for the maintenance of family history health information.
Interoperability between applications had been essentially non-existent. In 2007, the HL7 Pedigree standard has been approved by ANSI as a normative specification, and thus disparate family history applications can now easily exchange patient information.
The receiving application can understand the semantics of the incoming family history and enable the user to view and/or to edit that data using the receiving applications interface.
This US-Realm specific Implementation Guide (IG) of the Pedigree standard provides guidance on the use of the standard in the US by illustrating the preferred representation formats of key data elements such as genetic findings and clinical data. This guide also provides guidance on the exchange mechanism of family health data. Note that the guidance included in this IG accommodates the US Meaningful Use requirements regarding family health history.
In this first release of the US Guide, the guidance relates to merely demographc and clinical data. For details on the way genetic data could be represented as well as how risk assessment results coujld be captured, please refer to the ANSI standard (HL7 Pedigree R1) as well as to an informative document titled “HL7 Clinical Genomics Family History Model R2 - US Realm Implementation Guide – Genetic Data” that provides XML examples.
To do:
- refer to MU Stage 2 & 3 requirements regarding family health history and describe how it’s related to this IG
- add portion on minimal core dataset
- add alignment with ONC personalized healthcare use case and HITSP work
- describe Pedigree pilots in multiple diverse clinical settings (e.g. genetic testing lab, clinicians office, mammography center) and disease areas (e.g. cardiology, cancer, and prenatal/ObGyn).
- Mention usage by My Family Health Portrait and available for as open source software for integration into systems
2 storyboards
This section describes ….
2.1 Cancer - BRCA
The objective of this storyboard is to illustrate the way a patient's pedigree could be represented for risk analysis purposes in the context of breast and ovarian cancers and other diseases. The context for this storyboard is set by the broader breast cancer storyboard and includes a sample outline for the patient's pedigree. Note that the storyboard presneation has references to genetic data but as aformenetioned, this first release fo the US guide provides guidance to merely demographic and clinical data. Thus, the storyboard will remain the same acrossd future versions and releases of this guide.
2.1.1 Storyboard Presentation
1. Ms. Eve Everywoman has a family history of breast and ovarian cancer, and she is not of Ashkenazi Jewish descent.
2. She believes she is at high risk of developing breast cancer.
3. She goes to see her clinician (Medical oncologist, surgical oncologist, radiation oncologist, primary care provider) who takes a thorough family history. This history is recorded in the chart and the electronic medical record.
4. The clinician reviews the family history, decides what genetic syndrome her family might have, and categorizes the patient as to degree of risk (Perhaps high, medium, or low risk). The clinician thinks the patient is at high risk of having a BRCA1/2 mutation.
5. The clinician compares her Family History to tables of risk (Claus, Myriad) and runs computer models (algorithms such as BRCAPRO, see http://www.isds.duke.edu/~gp/brcapro.html). This gives a percentage risk of carrying a mutation and/or a risk of developing breast and/or ovarian cancer. Her risk of a mutation is 25%, because her father's 4 sisters had ovarian caner.
6. The patient is considered to be at high risk of having a mutation, and this information is given to her.
7. She is referred to a Risk Clinic.
8. She agrees to go to the Risk Clinic.
9. Ms Eve Everywoman 's Genetic History details are sent to this clinic (the HL7 Interaction POCG_IN000001 is used), including her Family History, the syndrome suspected and her level of risk.
10. The counselor at the risk clinic (Nurse geneticist, genetic counselor, MD, etc.) reviews the family history information collected by the primary clinician, edits it and adds additional details.
11. The Counselor reviews the family history, decides what genetic syndrome her family might have, and categorizes the patient as to degree of risk (Perhaps high, medium, or low risk). The Counselor thinks the patient is at high risk of having a BRCA1/2 mutation.
12. The clinician compares the family history to tables of risk (Claus, Myriad) and runs computer models (algorithms such as BRCAPRO). This gives a percentage risk of carrying a mutation and/or a risk of developing breast and/or ovarian cancer. Her risk of a mutation is 25%, because her father's 4 sisters had ovarian caner.
13. The patient is considered to be at high risk, and she is told she is a candidate for genetic testing. This includes a thorough discussion of the pros and cons of testing. This discussion is recorded in the electronic medical record.
14. Ms. Eve Everywomanwants to have testing, but as she is not affected, it is the standard of care to test a living affected relative first.
15. The Counselor suggests that her Aunt, Ms. Jeanne Aunt, is the most appropriate candidate for testing. Ms. Jeanne Aunt had ovarian caner, and is still living.
16. Ms. Eve Everywoman agrees to contact Ms. Jeanne Aunt.
17. Ms Eve Everywomansigns consent to release her own Family History details to Ms Jeanne Aunt and her Provider.
18. Ms. Jeanne Aunt is a 39-year-old woman had been diagnosed with ovarian cancer at age 35.
19. Ms Jeanne Aunt agrees to discuss testing, and provides the name and address of the Risk Clinic she will attend.
20. Ms Eve Everywoman's FH details are sent to this clinic.
21. The counselor at the risk clinic (Nurse geneticist, genetic counselor, MD, etc.) reviews the family history information collected by the primary clinician through a pedigree drawing program, and changes the Proband[3] to Ms Jeanne Aunt, edits it and adds additional details (The family history message had had Ms Eve Everywomanas the Proband (Self), and Ms Jeanne Aunt as the aunt. The pedigree from the point of view of Ms Jeanne Aunt must have Jeanne Aunt as the Proband (Self) and must show Ms Eve Everywomanas the niece).
22. The Counselor reviews the family history, decides what genetic syndrome her family might have, and categorizes the patient as to degree of risk (Perhaps high, medium, or low risk). The Counselor thinks the patient is at high risk of having a BRCA1/2 mutation.
23. The clinician compares the family history to tables of risk (Claus, Myriad) and runs computer models (algorithms such as BRCAPRO). This gives a percentage risk of carrying a mutation and/or a risk of developing breast and/or ovarian cancer. Ms. Jeanne Aunt is virtually at 100% risk of having a mutation.
24. The patient is considered to be at high risk, and she is told she is a candidate for genetic testing. This includes a thorough discussion of the pros and cons of testing. This discussion is reviewed in the electronic medical record.
25. Ms. Jeanne Aunt wants to have testing. She signs an informed consent document.
26. The order for testing is issued, and the informed consent, and the family history are included with the lab requisition. All are MESSEGED to the blood drawing facility.
27. The blood is drawn, and sent to the central testing facility along wit the informed consent, the family history and the lab requisition.
28. At the central testing facility, the specimen is checked in, and the DNA is separated and PCRed.
29. Full gene sequencing of BRCA1 and BRCA 2 are undertaken.
30. The sequence is assessed for mutations.
31. Identified mutations are assessed for functional significance by determining if they are truncating (deleterious), or if they are irrelevant (No change in amino acid coded by that codon). All other mutations are compared to known mutations to determine if information is available on their functional significance.
32. The actual mutation, and the assessment of functional significance are sent to the counselor.
33. In this case, a mutation is identified in BRCA1 and the mutation is Deleterious.
34. The counselor discusses the result with the patient.
35. Management decisions (Screening, chemoprevention, prophylactic surgery) are probably beyond the scope of this storyboard.
36. Ms Jeanne Aunt agrees to share this information with Ms Eve Everywoman's Clinician.
37. This information is sent to Ms Eve Everywoman's Clinician.
38. Ms. Eve Everywoman wants to have testing. She signs an informed consent document.
39. The order for testing is issued, and the informed consent, and the family history are included with the requisition, as well as the results of Ms Jeanne Aunt’s test. All are messaged to the blood drawing facility.
40. The blood is drawn, and sent to the central testing facility along with the informed consent, the family history, the results of Ms Jeanne Aunt’s test, and the lab requisition.
41. At the central testing facility, the specimen is checked in, and the DNA is separated and PCRed.
42. Full gene sequencing is not needed. Testing only for the identified mutation is undertaken.
43. The DNA is assessed for that specific mutation.
44. The mutation is not found.
45. The normal result is sent to the counselor.
46. The counselor discusses the result with the patient.
47. Management decisions (Screening, chemoprevention, prophylactic surgery) are probably beyond the scope of this storyboard.
48. Table 1: Outline for Family History of a Cancer Patient
Data Element Name / ValueRelative Type (Self)
Cancer
Year Diagnosed
Age Diagnosed
Familial Syndrome Suspected
Mother ID
Father ID
Relative ID
Relative Type (Brother, Sister …)
Cancer
Year Diagnosed
Age Diagnosed
Syndrome Suspected
Mother ID
Father ID
Relative ID
Relative Type (Brother, Sister …)
Cancer
Year Diagnosed
Age Diagnosed
Syndrome Suspected
Mother ID
Father ID
…
2.2 Sample Pedigrees
2.2.1 Annie Proband:
Annie Proband is a 42 year old woman with a family history strongly indicating a hereditary breast ovarian cancer syndrome.. The pedigree below shows a maternal grandparent and cousin with breast cancer. Early age of onset (30) for her cousin’s breast cancer is another indicator of familial risk. In addition, her mother’s Ovarian cancer is an additional risk factor.
Figure 1: Common Visualization of a Family Health History: Breast Ovarian Cancer Syndrome
The XML representations of the above pedigrees can be found in the package containing this guide.
2.2.2 Indiviual with PKU:
This is the pedigree of an individual with Phenylketonuria(PKU) a recessive disease:
Test_AR DOB:01/01/1991 MRN: 999_AR
Figure 2: Common Visualization of a Family Health History: PKU
2.2.3 Indiviual with Dominantly Inherited Hypertrophic Cardiomyopathy:
This is the pedigree of an individual with dominantly inherited hypertrophic cardiomyopathy.
Test Dominant DOB:09/09/1909 MRN: 999
Figure 3: Common Visualization of a Family Health HIstory: Dominantly Inherited Hypertrophic Cardiomyopathy
2.2.4 Indiviual with an X-linked Dilated Cardiomyopathy:
This pedigree shows the family history of an X-linked dilated cardiomyopathy. X-linked dilated cardiomyopathy (XLDC, sometimes abbreviated as XLDCM) is a clinical phenotype of dystrophinopathy which is characterized by preferential myocardial involvement without any overt signs of skeletal myopathy. It is a familial myocardial disease that presents with lethal congestive heart failure in young males in their teens or early twenties. A significant portion of XLDC-patients carry mutations in the dystrophin gene.