Guidelines for Diagnosis and Management

429 Pages·2015·3.35 MB·English

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: [phone] or 888-326-2664 (US only)
1801 Willamette Street, Suite 200 FAX: [phone]
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 prescript ive, 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 recomm endations.
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 molecu lar pathways has become increasingly complex
and sophisticated. Genotype determination and mutation analysis for each
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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 care.
• Phenotypic and genotypic predictors of the natural history and outcome of
the disease are beginning to emerge. As the costs of full genomic analyses
continue to fall, we may expect the development of even more specific and
powerful methods of diagnosis and, hopefully, therapy.
• The identification of BRCA2 and other FA genes linked to breast cancer
susceptibility has brought an influx of new scientific talent and interest to
the field of FA research. The relev ance of these findings to heterozygotes
(carriers) is being evaluated.
• A growing cohort of post-transplant adult FA survivors presents new
medical surveillance and treatment issues that include the unknown issues
of aging with underlying FA, the pitfalls of pharmaceuticals commonly
used in adult medicine in persons with FA, and the common presentation of
anticipated post-transplant complications with the unknowns of alternative
presentations and treatment tolerance in individuals with FA.
• With increased longevity for patients with FA the management of
transfusion-acquired iron overload requires serious consideration.
• A series of major scientific publications on the role of aldehydes in FA has
markedly changed the focus of research inquiry and therapeutic strategy
in very recent years. These discoveries bear not only on the on-going
debate as to whether DNA damage is the primary biological mechanism
underlying FA disease pathology, but suggest that attention be turned
to understanding the relevance of limiting exposure of persons with FA
to exogenous and endogenous aldehydes, including alcohol. Finally,
this rapidly developing research has inspired development of new small
molecule therapies and other forms of intervention that might lessen
damage to FA stem cells, suppress malignant transformation, or both.
• The availability of pre-implantation genetic diagn osis (PGD) for FA and
for HLA determination provides a potential parental choice for securi ng a
HLA-matched umbilical cord stem cell transplantation.
• Evaluation of adult FA patients reveals a striking and ominous incidence
of squamous cell carcin omas (SCC), especially of the head and neck and
gynecological tract. This underscores the need for continuous monitoring
and more effect ive treatment options throughout the patient’s lifetime.
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