Fanconi Anemia: Clinical, Cytogenetic and Experimental Aspects

275 Pages·1989·10.6 MB·English

by  Arleen D. Auerbach Ph. D.

T. M. Schroeder-Kurth A. D.Auerbach
G.Obe (Eds.)
Fanconi Anemia
Clinical, Cytogenetic
and Experimental Aspects
With 69 Figures in 122 Separate Illustrations
Springer-Verlag Berlin Heidelberg New York
London Paris Tokyo
Professor Dr. med. Traute M.Schroeder-Kurth
Institut fUr Humangenetik und Anthropologie
der Universitat Heidelberg
1m Neuenheimer Feld 328
0-6900 Heidelberg 1
Federal Republic of Germany
Arleen D. Auerbach, Ph. D.
Laboratory for Investigative Dermatology
The Rockefeller University
1230 York Avenue
New York, NY 10021-6399, USA
Professor Dr. Giinter Obe
Universitat Gesamthochschule Essen
Fachbereich 9 Genetik
UniversitatsstraBe 5
0-4300 Essen 1
Federal Republic of Germany
ISBN-13: 978-3-642-74181-4 e-ISBN-13: 978-3-642-74179-1
001: 10.1007/978-3-642-74179-1
Library of Congress Cataloging·in-Publication Data
Fanconi anemia: clinical, cytogenetic, and experimental aspects 1 T. M.Schroeder-Kurth,
A. D.Auerbach, G.Obe (eds.). p. cm. Includes index.
(U.S.)
1. Fanconi's anemia. I. Schroeder-Kurth, T. M. (Traute M.), 1930- II. Auerbach, A. D.
(Arleen D.), 1937- . III. Obe, G. RC641.7.F36F36 1989 616.1'52--dc19 88-38914 CIP
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© Springer-Verlag Berlin Heidelberg 1989
Softcover reprint of the hardcover I st edition 1989
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Preface
Sixty years ago, G. Fanconi published a paper entitled: "Familiiire
infantile pemiziosaartige Aniimie (pemizioses Blutbild und Konstitu
tion)", in which he reported that this type of severe aplastic anemia
represents a hereditary disease distinct from other pancytopenias
of childhood (Fanconi 1927). Later this syndrome was named Fan
coni anemia (FA; van Leeuwen 1933). A more recent study of the
genetics of FA confirmed that the syndrome is inherited in an au
tosomal recessive manner (Schroeder et al. 1976). Prenatal diagno
sis in FA families showed that about 25% of fetuses are affected
(Auerbach et al. 1985, 1986).
In 1964, Schroeder et al. discovered high frequencies of chro
mosomal aberrations in cultured peripheral blood lymphocytes
from patients with FA. Schuler et al. (1969) reported that cells from
FA patients are particularly sensitive to the chromosome-breaking
activity or clastogenic effect of a polyfunctional alkylating agent.
Since that time, studies of baseline and induced frequencies of
chromosomal aberrations have been used for the identification of
patients with FA. There is now a large body of data concerning the
possible mechanism(s) underlying the hypersensitivity of FA cells
to DNA cross-linking agents, the biochemical basis for which is
still unknown.
Complementation analysis, using cells from different FA pa
tients, has demonstrated genetic heterogeneity in the syndrome.
The new methods of gene technology are presently being applied
to the study of FA in an attempt to isolate and sequence the FA
gene(s). Unfortunately, we still have little knowledge of the molec
ular basis of the syndrome. Until a molecular probe is available for
use in diagnosis, there will continue to be difficulties in ascertain
ing and differentially diagnosing FA.
Five years ago, an International Fanconi Anemia Registry
(IFA R) was organized to provide a centralized computer database
for clinical, hematologic, and genetic information on FA patients.
Patients with clinical features of FA are registered, and then classi
fied according to their cellular sensitivity to DNA cross-linking
VIII Preface
agents. In the absence of a molecular probe, this is the best avail
able marker for the syndrome.
Recently it has been shown that in some cases the anemia in
FA patients can be cured by bone marrow transplantation. Thus
FA represents one of the riare inherited diseases which can be
treated successfully.
This book is intended to give an overview of our current know
ledge of FA, both clinical and experimental. We hope it will be
useful not only for specialists in the field, but also for others who
are interested in human genetic diseases.
We thank Springer-Verlag, particularly Dr. J. Wieczorek, and
Mrs. R. Till from the Institute of Human Genetics and Anthropolo
gy for their help in producing this book.
Heidelberg T. M. Schroeder-Kurth
New York A D. Auerbach
Essen G.Obe
References
Auerbach AD, Sagi M, Adler B (1985) Fanconi anemia: prenatal diagnosis in
30 fetuses at risk. Pediatrics 76: 794-800
Auerbach AD, Zhang M, Ghosh R, Pergament E, Verlinsky Y, Nicholas H,
Boue J (1986) Clastogen-induced chromosomal breakage as a marker for first
trimester prenatal diagnosis of Fanconi anemia. Hum Genet 73: 86-88
Fanconi G (1927) Familiare infantile perniziosaartige Anamie (pernizioses Blut
bild und Konstitution). Jahrb Kinderheilkd 117: 257-280
Schroeder TM, AnschUtz F, Knopp A (1964) Spontane Chromosomenaberra
tionen bei familiarer Panmyelopathie. Humangenetik 1: 194-196
Schroeder TM, Tilgen D, KrUger J, Vogel F (1976) Formal genetics of Fanconi's
anemia. Hum Genet 32: 257-288
Schuler D, Kiss A, Fabian F (1969) Chromosomal peculiarities and "in vitro"
examinations in Fanconi's anemia. Humangenetik 7: 314-322
van Leeuven HC (1933) Ein Fall von "konstitutioneller infantiler perniziosa
ahnlicher Anamie" (Fanconi) Folia Haematol (Leipz) 49: 434-443
Fig. 1. Three children affected with
Fanconi anemia
b
Fig. 2 a-c. Some radial
anomalies in three children
with Fanconi anemia.
a Preaxial polydactyly on
both hands. b Missing
thumb (left hand) and short,
misplaced thumb (right
c hand). c Typical radial
aplasia with absent thumb
Fig. 3 a-d. Three-year-old female with Fanconi anemia. The physical findings
are: low-set ears, stenotic ear canals, hearing loss (a), multiple cafe-au-Iait
spots, severe growth retardation (b), absent left thumb and radius, bowed and
shortened ulna, with scar from pollicization of index finger; right thumb pe
dunculated, treated by removal and pollicization of index finger (c), bilateral
second and third toe syndactyly (d). Large hematoma and ecchymoses between
eyes from a recent fall

Table of Contents
Part I Clinical and Therapeutical Aspects
International Fanconi Anemia Registry: First Report
A.D.Auerbach, A.Rogatko, and T.M.Schroeder-Kurth . 3
Fanconi Anemia in The Netherlands
M. L. Kwee and L. P. Kuyt . . . . . . . . . . . . . . . . . . 18
Clinical Aspects of a Cluster of 42 Patients in South Africa
with Fanconi Anemia
S. Smith, M. P. Marx, C. J. Jordaan, and C. H. van Niekerk .. 34
Therapeutic Aspects of Fanconi Anemia
W. Ebell, W. Friedrich, and E. Kohne . . . . . . . . . . . . 47
Bone Marrow Transplantation for Fanconi Anemia
E. Gluckmann, A. Devergie, and J. Dutreix . . . . . . . . 60
Part II Spontaneous and Induced Chromosomal
Breakage for Diagnosis of Patients with Fanconi Anemia
and Their Relatives
Diepoxybutane Test for Prenatal and Postnatal Diagnosis
of Fanconi Anemia
A. D.Auerbach, R. Ghosh, P. C. Pollio, and M. Zhang . . . . 71
Chromosomal Breakage in Response to Cross-linking Agents
in the Diagnosis of Fanconi Anemia
F. Arwert and M. L. K wee . . . . . . . . . . , . . . . . . . 83
Cytogenetic Studies in Fanconi Anemia: Induced
Chromosomal Breakage and Cytogenetics of Leukemia
R. Berger and M. Le Coniat . . . . . . . . . . . . . . . .. 93
Aplastic Anemia and Fanconi Anemia: Response
of Lymphocytes to X-Rays and Mitomycin C
A. T. Natarajan, J. M. J. J. Vossen, and M. H. van Weel-Sipman . 100
Variation in Cellular Sensitivities Among Fanconi Anemia
Patients, Non-Fanconi Anemia-Patients, Their Parents and
Siblings, and Control Probands
T.M.Schroeder-Kurth, T.H.Zhu, Y.Hong, and I. Westphal . .. 105