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Guidelines for Diagnosis and Management, Fourth Edition Fanconi Anemia: Guidelines for Diagnosis and Management Fourth Edition • 2014 We are deeply grateful to the following generous donors, who made this publication possible: Pat and Stephanie Kilkenny Phil and Penny Knight Disclaimer Information provided in this handbook about medications, treatments or products should not be construed as medical instruction or scientific endorsement. Always consult your physician before taking any action based on this information. copyright© 1999; second edition 2003; third edition 2008; fourth edition 2014 Fanconi Anemia: Guidelines for Diagnosis and Management Fourth Edition • 2014 Managing Editor: Laura Hays, PhD Editors: Dave Frohnmayer, JD, Lynn Frohnmayer, MSW, Eva Guinan, MD, Teresa Kennedy, MA, and Kim Larsen Scientific Writers: SciScripter, LLC These guidelines for the clinical care of Fanconi anemia (FA) were developed at a conference held April 5-6, 2013 in Herndon, VA. We owe a tremendous debt of gratitude to Eva Guinan, MD, for serving as moderator of the conference, as she did for the consensus conferences for the first three editions, and for her skill in helping the participants arrive at consensus. We would like to thank all the participants for donating their time and expertise to develop these guidelines. The names and contact information of all participants appear in the Appendix. These guidelines are posted on our Web site and are available from: Fanconi Anemia Research Fund, Inc. Phone: 541-687-4658 or 888-326-2664 (US only) 1801 Willamette Street, Suite 200 FAX: 541-687-0548 Eugene, Oregon 97401 E-mail: [email protected] Web site: www.fanconi.org Facebook: www.facebook.com/fanconianemiaresearchfund Twitter: https://twitter.com/FAresearchfund Material from this book may be reprinted with the permission of the Fanconi Anemia Research Fund, Inc. The Fanconi Anemia Research Fund, Inc., was founded in 1989 to provide support to FA families and to raise money for scientific research. The Fund publishes a newsletter twice a year, sponsors an annual family meeting and a meeting for adults with FA every 18 months, and provides resource identification and counseling support to families. To aid research into FA, the Fund gives grants to scientists and sponsors scientific conferences, including an annual scientific symposium. Board of Directors Advisor to the Board Barry Rubenstein, JD, President David Frohnmayer, JD Lynn Frohnmayer, MSW, Vice President Scientific Advisory Board Brian Matthews, PhD, Secretary/Treasurer Grover C. Bagby, Jr., MD, Chair Christopher Byrd, Esq. Joseph Califano, MD David Fiaschetti, DDS Richard Gelinas, PhD Amy Frohnmayer, MA Eva Guinan, MD Richard Gelinas, PhD Christopher Mathew, PhD Brian Horrigan Stephen Meyn, MD, PhD Kevin McQueen Raymond J. Monnat, Jr., MD Mark Pearl Elaine Ostrander, PhD Peter Pless, MD Bhuvanesh Singh, MD, PhD Sharon Schuman, PhD Elizabeth Swisher, MD Annette Waxberg, MBA Jakub Tolar, MD, PhD William N. William, Jr., MD Staff Laura Hays, PhD, Executive Director Teresa Kennedy, MA, Director of Family Support Services Cynthia Freeman, Special Projects Coordinator Kristi Keller, Administrative Assistant and Bookkeeper Kim Larsen, Conference Planner and Communications Editor Special thanks to the following authors who made major writing contributions: Blanche P. Alter, MD, MPH, FAAP (Chapter 15) Farid Boulad, MD (Chapter 12) Mercedes Castiel, MD (Chapter 6) Nancy F. Cincotta, MSW, MPhil (Chapter 18) David K. Fiaschetti, DDS (Chapter 10) Lynn Frohnmayer (Chapter 19) Alfred Gillio, MD (Chapter 16) Neelam Giri, MD (Chapter 7) Helmut Hanenberg, MD (Chapters 1 and 3) H. Jeffrey Kim, MD (Chapter 8) Betsy Hirsch, PhD, FACMG (Chapter 2) Sally Kinsey, MD (Chapters 1 and 3) Scott H. Kozin, MD (Chapter 5) David Kutler, MD (Chapter 14) Jeffrey M. Lipton, MD, PhD (Chapters 1 and 3) Jennifer Y. Lin, MD (Chapter 9) Margaret MacMillan, MD (Chapter 20) Susan Olson, PhD, FACMG (Chapter 2) Anna Petryk, MD (Chapter 7) Susan R. Rose, MD (Chapter 7) Philip S. Rosenberg, PhD (Chapter 15) Erica Sanborn, MS (Chapter 17) Mark M. Schubert, DDS, MSD (Chapter 10) Sarah Jane Schwarzenberg, MD (Chapter 4) Roopa Kanakatti Shankar, MD, MS (Chapter 7) Akiko Shimamura, MD, PhD (Chapter 3) Bhuvanesh Singh, MD, PhD (Chapter 14) Pamela Stratton, MD (Chapter 6) Flavia R. Teles, DDS, MS, DMSc (Chapter 10) Jakub Tolar, MD, PhD (Chapter 13) John Wagner, MD (Chapter 11) William William, MD (Chapter 14) Heather Zierhut, PhD, MS, CGC (Chapter 17) Table of Contents Introduction ...........................................................................................................................1 Chapter 1: Diagnosis and Evaluation.........................................................................................6 Chapter 2: Laboratory Diagnostics ..........................................................................................27 Chapter 3: Hematologic Abnormalities in Patients with Fanconi Anemia ....................................43 Chapter 4: Gastrointestinal, Hepatic, and Nutritional Problems ................................................74 Chapter 5: Hand and Arm Abnormalities .................................................................................99 Chapter 6: Issues Facing Women with Fanconi Anemia: Improved Survival and New Dilemmas ...121 Chapter 7: Endocrine Disorders ..........................................................................................142 Chapter 8: Hearing and Ear Abnormalities in Fanconi Anemia .................................................177 Chapter 9: Dermatologic Issues ...........................................................................................194 Chapter 10: Oral and Dental Health Care .............................................................................201 Chapter 11: Hematopoietic Stem Cell Transplantation ...........................................................217 Chapter 12: Long-Term Follow-Up After Transplantation .......................................................242 Chapter 13: Novel Stem Cell Treatment Options ...................................................................257 Chapter 14: Head and Neck Cancers in Patients with Fanconi Anemia ....................................269 Chapter 15: Non-Head and Neck Solid Tumors in Patients with Fanconi Anemia ......................285 Chapter 16: The Adult Patient with FA ..................................................................................294 Chapter 17: Genetic Counseling ...........................................................................................306 Chapter 18: Psychosocial Issues .........................................................................................333 Chapter 19: The Grieving Process and the Physician’s Role: A Mother’s Perspective ................352 Chapter 20: Clinical Management Checklist ..........................................................................367 Abbreviations and Important Terms ...................................................................................382 Appendix ............................................................................................................................394 Index ..................................................................................................................................401 Introduction Fanconi Anemia: Guidelines for Diagnosis and Management, Fourth Edition, is the result of a Consensus Conference held by the Fanconi Anemia Research Fund in Herndon, Va., April 5-6, 2013. It replaces earlier editions published in 1999, 2003, and 2008. These guidelines are published for physicians who provide care for FA patients, and for patients and families who wish to secure optimal treatment by improving their understanding of all facets of Fanconi anemia, medical consultation, and appropriate referral. These guidelines begin with detailed information on diagnosis and evaluation of FA. Subsequent chapters examine more specific health issues faced by persons with FA, followed by two chapters on psychosocial considerations that bear upon the well-being of the person with FA and his or her extended family. The guidelines conclude with a comprehensive checklist and diagnostic criteria for physicians and medical specialists. Where possible, the guidelines rely on evidence-based medicine. Where adequate data are lacking because of limitations of numbers, time frame, or present knowl edge, the consensus of expert opinion underlies the rec- ommendations. Every effort has been made to give fair voice to discordant medical opinions when evidence is lacking and controversy exists. All chapters have been peer-reviewed and describe best practices as of the date of publication. To avoid being excessively prescriptive, the title of this book was changed in our last edition from “Standards” to “Guidelines.” From the discussions at this and earlier Consensus Conferences, the authors realize that a more robust clinical database must be developed to gather additional evidence upon which to base recommendations. FA-related science has significantly advanced since the last publication in 2008: • At least 16 FA genes now have been identified. The understanding of interactions among molecular pathways has become increasingly complex and sophisticated. Genotype determination and mutation analysis for each 1 Fanconi Anemia: Guidelines for Diagnosis and Management patient bear directly on the appropriateness of some treatment choices and it is anticipated that this information will become increasing relevant to patient
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