American Journal of Medical Genetics 124A:35 39 (2004)

DEB Test for Fanconi Anemia Detection

in Patients With Atypical Phenotypes
Carmen Esmer, Silvia Sanchez, Sandra Ramos, Bertha Molina, Sara Frias, and Alessandra Carnevale*
Department of Research in Human Genetics, National Institute of Pediatrics, Mexico City, DF, Mexico

Pancytopenia, hyperpigmentation, small

stature, congenital abnormalities, and predisposition to neoplasia characterize Fanconi
anemia (FA). The clinical phenotype is extremely variable, therefore the diagnosis is
frequently delayed until the pancytopenia
appears, making diagnosis difficult on the
basis of clinical manifestations alone. Hypersensitivity of FA cells to the clastogenic effect
of diepoxybutane (DEB) provides a unique
marker for the diagnosis before the beginning of hematological manifestations. Our
aim in this study was to detect FA in children
with atypical manifestations to define which
conditions should be routinely included in
the DEB test screening. We performed the
chromosomal breakage test in 34 patients
with probable FA and 83 patients with clinical conditions that could suggest FA, but
are not usually screened by the DEB test:
20 patients with aplastic anemia, 20 patients
with VACTERL association, 20 with radial
ray abnormalities, 7 with tracheo-esophageal
fistulae, 12 with anal atresia, and 4 with
myelodysplastic syndrome. We found 18 DEBpositive patients: 12 were in the group of
probable FA and 6 in the other groups.
Among the last ones: three were included
because of aplastic anemia, without any
other sign of FA, however when re-examined,
other anomalies were detected. The third
patient had anal atresia, renal hypoplasia,
pre-axial polydactyly, and normal blood cell
counts and was diagnosed as having VACTERL association. The other two patients

Grant sponsor: CONACYT; Grant numbers: 29140-M, 3388-M;

Grant sponsor: CONACYT (to C.E.); Grant number: 91769.
*Correspondence to: Dr. Alessandra Carnevale, Department of
Research in Human Genetics, National Institute of Pediatrics,
Insurgentes Sur 3700-C, 04530, Mexico.
E-mail: carneval@sni.conacyt.mx
Received 12 September 2002; Accepted 8 April 2003
DOI 10.1002/ajmg.a.20327

2003 Wiley-Liss, Inc.

lacking physical or hematological signs were

identified among the group of radial ray
abnormalities. Thus, our results highlight
the need to increase the number of abnormalities indicating need for a DEB test. Delay
in the diagnosis of FA may have serious consequences for the patients and their family
members. 2003 Wiley-Liss, Inc.
KEY WORDS: Fanconi anemia; chromosome breakage; diepoxybutane
test;
congenital
anomalies; VACTERL

INTRODUCTION
Fanconi anemia (FA) was first described in 1927
[Gordon and Rutherford, 1989]. It is an autosomal
recessive disorder with prevalence between 1/26,000
and 1/476,000 in different geographic regions [Macdougall
et al., 1994; Altay et al., 1997]. Until 1992, approximately 1,000 patients had been reported.
Among the most constant clinical characteristics are:
pancytopenia, growth delay, and skin hyperpigmentation present in over 60% of patients [Alter, 1993]. The
most frequent associated malformations are those of the
skeletal system, mainly of the radius and thumb. Less
than 50% have renal, genital, ocular, hearing, or heart
abnormalities [Alter, 1992; Porteus et al., 1992]. The
presence of malformations such as anal atresia, cardiac
defects, tracheo-esophageal fistula in FA patients may
lead to confusion with other entities such as the
VACTERL association or the BallerGerold syndrome
[Porteus et al., 1992; Rossbach et al., 1996; Perel et al.,
1998]. Approximately 20% of patients develop some
type of neoplasia, mainly hematological (leukemias) and
carcinomas, particularly liver cancer [DAndrea and
Grompe, 1997]. Generally, a FA patient has 15,000
times greater risk of developing cancer in pediatric ages
[Gordon and Rutherford, 1989; Alter, 1993], and it has
been reported that in 24% of FA patients developing
leukemia, this is the first symptom. The type of leukemia
seen with greatest frequency is acute myeloid leukemia
preceded or not by a myelodysplasic syndrome [Alter,
1996]. The FA clinical picture is extremely variable, up
to 37% of patients does not have associated congenital
malformations [Giampietro et al., 1997] and in such

36

Esmer et al.

cases the diagnosis is not made until the onset of

pancytopenia. This hematological manifestation, which
is present in 90% of cases, also behaves variably, is seen
in several degrees of severity, and starts at variable
ages [Gordon and Rutherford, 1989]. Although most of
patients are diagnosed between 3 to 7 years of age based
on the presence of pancytopenia, in 10%, the diagnosis is
made after the age of 16. The age range for diagnosis
varies between 0 and 38 years and the most frequent initial hematological manifestation is thrombocytopenia. It may be said that the clinical picture has a
continuous spectrum of manifestations. Some patients
have a relatively mild condition with normal skeletal
development, subclinical hematopoietic abnormalities,
surviving until the fourth or fifth decade of life. On the
other end of the scale, there are patients with severe
phenotype, multiple skeletal abnormalities, and an early
onset of aplastic anemia and/or cancer. There are also
atypical clinical conditions without anemia, of late onset
[Auerbach et al., 1989; Giampietro et al., 1997], or with
initial conditions that may be confused with other syndromes, as those mentioned earlier.
The definite diagnosis of FA is established when the
peripheral blood lymphocytes show a response to mitomycin C or diepoxybutane (DEB) 310 times greater
than a normal control. Comparative studies show that
the DEB test provides a highly sensitive and specific test
given that the chromosomal response of FA patients
cannot be confused with the response of a normal control
[Schroeder et al., 1964; Sasaki and Tonomura, 1973;
Frias et al., 1986; Auerbach et al., 1989; Auerbach,
1993].
Although the DEB test is highly effective in discriminating FA from other conditions, it remains underutilized mainly because there are some clinical
conditions in which FA is not usually suspected. The
purpose of this study was to screen patients with
manifestations related to the FA phenotype using the
DEB test that are not usually screened, in order to
detect FA patients in this group of children with atypical
manifestations and to define which conditions should
be included in the routine screening of the disease.
MATERIALS AND METHODS
Patients
Patients were referred to the Cytogenetics Laboratory
from the Outpatient Clinic at the National Institute
of Pediatrics in Mexico City, and from three other
medical centers on the basis of the clinical characteristics established for each of five groups, as follows:
1. Probable FA: patients with aplastic anemia, short
stature, hyperpigmentation, and typical congenital
abnormalities;
2. Aplastic anemia: patients with aplastic anemia
without any other finding;
3. VACTERL association: patients with
2 malformations such as vertebral or radial ray abnormalities,
anal atresia, tracheo-esophageal atresia, congenital
cardiovascular malformations;

4. Radial ray abnormalities, anal atresia, or tracheoesophageal atresia: patients with one of these isolated
congenital anomalies;
5. Myelod abnormalities: patients with myelodysplasic
syndrome or myeloid leukemia.
Chromosome Breakage Studies
Blood samples were obtained from each patient for
chromosomal instability studies, including testing for
hypersensitivity to the clastogenic effect of the DNA
cross-linking agent DEB. The cytogenetic diagnosis was
conventionally made in peripheral blood lymphocytes
stimulated with phytohemagglutinin in 72 hr cultures
[Frias et al., 1986; Auerbach, 1993], 0.5 ml of heparinized blood added to 5 ml of medium. Cultures were
paired for DEB studies, with a replicate set of cultures to
serve as untreated controls. DEB, at a final concentration in the medium of 0.1 mg/ml, was added to the treated
cultures; dilutions were prepared just before addition of
DEB to cell cultures. Untreated cultures were set and
processed under the same conditions. In addition, for
each patient, a unmatched control was studied with the
same methodology. Control subjets were phenotypically
normal individuals of both sexes ranging in age from 21
to 28 years, free of drugs, alcohol, or smoking habits who
signed the informed consent to voluntarily participate
in the study. Slides were prepared and codified for the
blind analysis of chromosome aberrations. Analysis
was performed on 50 Giemsa-stained metaphases, each
cell was scored for chromosome number and for the
numbers and types of structural abnormalities. Achromatic areas, less than a chromatid in width, were
excluded in the calculation of chromosome breakage
frequencies, while exchange configurations, translocations, dicentric and ring chromosomes were scored as
one chromosomal aberration. A patient was diagnosed
as having FA when the frequency of breaks/cell was at
least six times the frequency in the control lymphocyte
culture.
RESULTS
One hundred and seventeen patients were studied:
34 in Group 1 with probable FA; 20 in Group 2 with
only aplastic anemia; 20 in Group 3 with VACTERL
association; 39 patients in Group 4: 20 with radial ray
abnormalities, 7 with tracheo-esophageal atresia or
fistula, and 12 with anal atresia; and in Group 5, four
patients with myeloid abnormalities.
Among the 34 patients (Group 1) referred because
they had some clinical findings consistent with FA,
12 were diagnosed as affected based on the DEB test
(Table I). Table II shows the most frequent findings in
FA and non-FA patients in this group. The main clinical
manifestation in this groups FA patients was aplastic
anemia in all of the patients, associated with other
findings such as hyperpigmentation (83%) and suggestive FA facial anomalies (66%), as contrasted with
the non-FA group where only 77% of patients had
anemia and 18% had hyperpigmentation or the minor
anomalies. Short stature was seen with the same

AF in Patients With Atypical Phenotypes

TABLE I. Chromosomal Breakage in Peripheral Blood
Lymphocytes of Group 1 Patients With Probable FA
Spontaneous
(breaks/cell)
Patients

Control

Patient

0.04
0.33
0.76
0.12
0.0
0.0
0.28
0.24
0.32
0.32
0.04
0.08
0.12
0.22
0.08
0.0
0.08
0.02
0.04
0.12
0.28
0.20
0.12
0.0
0.0
0.0
0.04
0.0
0.12
0.04
0.24
0.0
0.0
0.32

0.04
0.04
0.04
0.0
0.04
0.0
0.0
0.0
0.0
0.04
0.04
0.0
0.0
0.0
0.04
0.04
0.08
0.0
0.08
0.0
0.04
0.04
0.0
0.24
0.0
0.0
0.0
0.0
0.08
0.04
0.04
0.0
0.08
0.04

0.12
3.17
5.72
4.32
0.0
0.04
2.84
5.86
3.2
2.84
0.04
0.0
0.12
2.44
0.08
0.0
0.04
0.12
0.12
0.04
0.04
0.32
0.2
0.0
0.04
0.08
2.84
0.04
0.08
1.68
1.39
0.08
0.0
3.44

AF1
AF2a
AF3a
AF4a
AF5
AF6
AF7a
AF8a
AF9a
AF10a
F11
AF12
AF13
AF14a
AF15
AF16
AF17
AF18
AF19
AF20
AF21
AF22
AF23
AF24
AF25
AF26
AF27a
AF28
AF29
AF30a
AF31a
AF32
AF33
AF34a
a

TABLE III. Chromosomal Aberration in Peripheral Blood

Lymphocytes From Group 2 Patients With Aplastic Anemia
Spontaneous
(breaks/cell)

DEB (breaks/cell)

Patient

Control
0.08
0.0
0.08
0.0
0.0
0.04
0.0
0.08
0.04
0.08
0.12
0.08
0.0
0.08
0.08
0.08
0.04
0.0
0.04
0.08
0.08
0.0
0.12
0.24
0.04
0.0
0.08
0.12
0.16
0.04
0.04
0.08
0.12
0.04

Patients
AA1
AA2
AA3
AA4
AA5
AA6
AA7
AA8
AA9
AA10a
AA11a
AA12
AA13
AA14b
AA15
AA16
AA17
AA18
AA19
AA20

Patient

Control

Patient

Control

0.04
0.0
0.0
0.08
0.0
0.48
0.08
0.0
0.04
0.12
0.24
0.0
0.04
0.12
0.16
0.08
0.0
0.16
0.08
0.08

0.04
0.0
0.0
0.12
0.04
0.04
0.04
0.0
0.12
0.04
0.0
0.08
0.0
0.16
0.2
0.04
0.04
0.04
0.04
0.0

0.0
0.2
0.12
0.04
0.04
0.04
0.04
0.04
0.0
4.5
4.32
0.12
0.12
1.32
0.16
0.04
0.08
0.08
0.04
0.08

0.0
0.2
0.04
0.04
0.08
0.0
0.04
0.0
0.04
0.0
0.0
0.08
0.04
0.36
0.04
0.08
0.24
0.12
0.12
0.08

positive (Table IV). On physical examination, performed

after the diagnosis, hyperpigmentation, minor facial
anomalies, and short stature were also found. The
patient was not anemic at the time of the study but a
year later started with thrombocytopenia.
TABLE IV. Lymphocyte Chromosomal Aberration in Group 3
Patients With VACTERL Association

frequency in both groups. FA patients had four or

more abnormalities, while non-FA subjects had three of
them. In Group 2, including 20 patients with aplastic
anemia, 3 were diagnosed as having FA (Table III).
Two were 12- and 8-year-old boy patients, one with a
renal anomaly, and the other had hypoplasia of the first
metacarpal bone. The third was a 6-year-old girl with
aplastic anemia and short stature. Among the patients
with VACTERL association (Group 3), one with anal
atresia, polydactyly, and renal hypoplasia was DEB

TABLE II. Clinical Manifestations of Group 1 Patients According

to the Diagnosis (FA and Non-FA)

Aplastic anemia
Short stature
Hyperpigmentation
Suggestive facies
Radial ray abnormalities
Renal malformation

DEB (breaks/cell)

On the DEB test the FA patient shows exchange configurations and

chromosomal breaks while control only shows chromosomal breaks.
a
DEB positive patients.
b
Additional MMC test was performed: 3.84 ab/cell (patient) vs. 0.12 ab/cell
(control).

DEB positive patients.

Characteristics

37

FA (n 12) (%)

Non-FA
(n 22) (%)

12 (100)
11 (91)
10 (83)
8 (66)
7 (58)
2 (16)

17 (77)
20 (90)
4 (18)
4 (18)
15 (68)
5 (22)

Spontaneous
(breaks/cell)
Patients
V1
V2
V3
V4
V5
V6
V7
V8
V9a
V10
V11
V12
V13
V14
V15
V16
V17
V18
V19
V20
a

DEB positive.

DEB (breaks/cell)

Patient

Control

Patient

Control

0.0
0.0
0.04
0.08
0.0
0.04
0.0
0.04
0.28
0.12
0.08
0.04
0.0
0.12
0.0
0.2
0.16
0.04
0.04
0.12

0.0
0.04
0.08
0.0
0.0
0.0
0.04
0.08
0.04
0.0
0.04
0.0
0.04
0.08
0.04
0.04
0.12
0.04
0.0
0.0

0.08
0.04
0.0
0.04
0.2
0.08
0.0
0.0
4.4
0.04
0.32
0.12
0.04
0.08
0.04
0.28
0.08
0.04
0.12
0.16

0.0
0.08
0.08
0.08
0.0
0.04
0.08
0.0
0.04
0.0
0.16
0.12
0.04
0.24
0.08
0.12
0.04
0.04
0.12
0.0

38

Esmer et al.

In Groups 4 and 5, where patients with only one

anomaly (renal, radial, anorrectal, or myeloid) were
included, two FA newborn patients were detected among
those with isolated radial ray abnormalities, they have
absence of thumbs and low birth weight and normal
blood cell counts (Tables V, VI).
Therefore among the 117 patients included, we found
18 with chromosomal instability exhibiting a higher
frequency of breaks after DEB exposure. Analysis of
baseline chromosomal breakage in the FA group showed
that the patients frequency differs from that found in
normal controls or in the non-FA group. The range of
breakage in untreated cells was 0.041.6 breaks/cell
(mean 0.30) for the FA patients and 00.48 breaks/cell
(mean 0.07) for the non-FA group. There were no significant differences in the baseline breakage frequencies
TABLE V. Chromosomal Breakage in Peripheral Blood
Lymphocytes in Group 4 Patients With Single
Congenital Malformations
Spontaneous (breaks/cell)
Patients

Patient

Esophageal atresia
AE1
0.0
AE2
0.04
AE3
0.2
AE4
0.0
AE5
0.08
AE6
0.04
AE7
0.04
Radial ray abnormality
R1
0.0
R2
0.04
R3
0.08
R4
0.08
R5
0.24
R6
0.0
a
0.16
R7
R8
0.04
R9
0.12
R10
0.16
R11
0.40
R12
0.04
R13
0.04
R14
0.0
R15
0.04
R16
0.2
R17
0.08
R18
0.04
R19
0.04
a
1.60
R20
Anorectal malformation
AR1
0.12
AR2
0.0
AR3
0.12
AR4
0.08
AR5
0.08
AR6
0.04
AR7
0.24
AR8
0.0
AR9
0.04
AR10
0.2
AR11
0.0
AR12
0.16
a

DEB positive patients.

DEB (breaks/cell)

Control

Patient

Control

0.0
0.0
0.0
0.0
0.08
0.08
0.0

0.04
0.08
0.0
0.0
0.2
0.16
0.08

0.16
0.04
0.0
0.0
0.28
0.28
0.04

0.0
0.02
0.0
0.0
0.0
0.0
0.0
0.08
0.04
0.04
0.04
0.04
0.0
0.0
0.04
0.04
0.04
0.04
0.04
0.12

0.02
0.08
0.0
0.08
0.24
1.44
3.84
0.04
0.17
0.08
0.72
0.0
0.0
0.08
0.04
0.0
0.08
0.04
0.10
3.0

0.12
0.16
0.0
0.12
0.24
1.68
0.04
0.04
0.0
0.2
0.0
0.12
0.0
0.20
0.20
0.12
0.0
0.04
0.0
0.0

0.0
0.04
0.04
0.32
0.12
0.0
0.24
0.16
0.08
0.08
0.12
0.12

0.04
0.04
0.0
0.04
0.12
0.08
0.0
0.04
0.24
0.04
0.16
0.04

0.0
0.04
0.0
0.16
0.04
0.04
0.24
0.2
0.08
0.08
0.16
0.16

TABLE VI. Chromosomal Breakage in Periferal Blood

Lymphocytes in Group 5 Patients With Myeloid Abnormalities
Spontaneous
(breaks/cell)
Patients
M1
M2
M3
M4

DEB (breaks/cell)

Patient

Control

Patient

Control

0.12
0.08
0.04
0.0

0.0
0.0
0.0
0.28

0.04
0.04
0.04
0.04

0.04
0.0
0.0
0.08

for these two groups. The mean DEB-induced chromosomal breakage in the FA group was 3.39 breaks/cell
(range 1.325.86), while the mean breakage frequency
for the non-FA patients was 0.09 breaks/cell (range 0
1.44). As expected, differences between FA vs. non-FA
or controls were statistically significant (Table VII).
DISCUSSION
FA is one of several disorders that have in common
the presence of increased chromosomal fragility or
cellular hypersensitivity to mutagenic chemicals, associated with developmental defects. Cells from FA patients are uniquely hypersensitive to the clastogenic
effect of DNA cross-linking agents such as DEB, and can
thus be distinguished from cells of the patients with
other syndromes on this basis.
Clinical diagnosis of FA is complicated because of
other disorders, both genetic and non-genetic, are characterized by many of the clinical manifestations seen
in FA. Familial associations of various combinations of
radial, renal, cardiac, hearing, growth, skin pigmentation, and hematologic abnormalities have been well
documented, and a number of different syndromes
delineated. Among these are dyskeratosis congenita,
TAR syndrome, HoltOram syndrome, Aase syndrome,
WT syndrome, Shwachman syndrome, IVIC syndrome,
and the VACTERL association. Thumb abnormalities have been reported in a number of patients with
BlackfanDiamond anemia. The extreme phenotypic
diversity associated with FA makes the availability of a
diagnostic laboratory test especially valuable.
In the present study we found 12/34 (30%) FA patients
among cases suspected of having FA on the basis of
anemia characteristic facial appearence, short stature,
hyperpigmentation, renal or radial ray anomalies. This
result coincides with that reported by Auerbach et al.
[1989], who found 104/328 (29%) patients with these
TABLE VII. Mean Chromosomal Breaks Among Controls, FA,
and Non-FA Patients

Control (n 117)
FA (n 18)
Non-FA (n 99)

Spontaneous
(breaks/cell)

Induced with DEB

(breaks/cell)

0.04
0.30
0.07

0.09
3.39
0.10

Control vs. spontaneous FA; P 0.006 (MannWhitney test).

Control vs. FA DEB 0.64; P 0.000 (MannWhitney test).

AF in Patients With Atypical Phenotypes

manifestations. Also, we found six FA patients among

groups that are not usually tested for chromosomal
breakage: three had aplastic anemia not associated with
other manifestation, agreeing with the expected 10%
reported by Auerbach et al. [1989]. One FA patient was
found among those with VACTERL association. The
frequency of FA in patients with VACTERL criteria
without aplastic anemia is still unknown, although 10%
of FA patients meet three of the diseases criteria and
20% meet two. Two newborn patients with isolated
radial ray malformation, were diagnosed as having FA,
which was particularly important both for genetic
family counseling, as well as for establishing surveillance on hematological manifestations. None out of
19 patients with a gastrointestinal abnormality were
affected, although 5.1% of the FA patients have anorectal anomalies and 3.5% have tracheal-esophageal
fistula as part of their clinical manifestations [Perel
et al., 1998]. No patients were affected in Group 5, but
the number should be increased, since it is known
that there are patients in which hematologic neoplasms
are the diseases initial manifestation, and that there
are variants in the FANCC sequence in patients with
acute myeloid leukemia [Awan et al., 1998].
Our results emphasize the importance of routinely
conducting a diagnostic test in patients with aplastic
anemia, with criteria of VACTERL association, or with a
radial ray anomaly without any other anomaly. On the
contrary, we suggest that patients with isolated intestinal abnormalities do not need the test. An accurate
diagnosis will influence the choice of therapy, considering that FA patients have a high response rate to treatment using androgens. Information regarding DEB
sensitivity is also extremely important in patients to
be treated with bone marrow transplantation or chemotherapy. Since FA patients are hypersensitive to
all DNA cross-linking agents, they require a modified
pre-transplantation conditioning regimen, with a lower
than usual dose of cyclophosphamide or lower doses of
chemotherapeutic agents [Alter, 1996; DAndrea and
Grompe, 1997].
In conclusion, the results of this study indicate that
FA patients are probably underdiagnosed and that
testing for hypersensitivity to the clastogenic effect of
DEB is a useful method for pinpointing FA cases from

39

other patients manifesting some of the clinical features

of the syndrome.
REFERENCES
Altay C, Alikasifoglu M, Kara A, Tuncbilek E, Ozbek N, Schroeder-Kurth
TM. 1997. Analysis of 65 Turkish patients with congenital aplastic
(Fanconi anemia and non-Fanconi anemia): Hacettepe experience. Clin
Genet 51:296302.
Alter BP. 1992. Fanconi anemia. Current Concepts. Am J Pedriatr Hematol
Oncol 14:170176.
Alter BP. 1993. Fanconis anaemia and its variability. Br J Haematol 85:
914.
Alter BP. 1996. Fanconis anaemia and malignancies. Am J Hematol 53:
99110.
Auerbach AD. 1993. Fanconi anemia diagnosis and the diepoxibutane (DEB)
test. Exp Hematol 21:731736.
Auerbach AD, Rogatko A, Schroeder-Kurt TM. 1989. International Fanconi
Anemia Registry: Relation of clinical symptoms to diepoxibutane
sensitivity. Blood 73:391396.
Awan A, Taylor GM, Gokhale DA, Dearden S, Will A, Stevens RF, Birch JM,
Eden T. 1998. Increased frequency of Fanconi anemia group C genetic
variants in children with sporadic acute myeloid leukemia. Blood
91:48134814.
DAndrea AD, Grompe M. 1997. Molecular biology of Fanconi anemia:
Implications for diagnosis and therapy. Blood 90:17251736.
Frias S, Carnevale A, y Del Castillo V. 1986. Utilidad de la prueba de
exposicion de linfocitos a mitomicina C en el diagnostico de anemia de
Fanconi. Rev Invest Clin 36:219224.
Giampietro PF, Verlander PC, Davis JG, Auerbach AD. 1997. Diagnosis of
Fanconi anemia patients without congenital malformations: An International Fanconi Anemia Registry Study. Am J Med Genet 68:5861.
Gordon EC, Rutherford TR. 1989. Fanconi anaemia-constitutional, familial
aplastic anaemia. Bailleres Clin Haematol 2:139151.
Macdougall LG, Rosendorff J, Poole JE, Cohn RJ, McElligott SE. 1994.
Comparative study of Fanconi anaemia in children of different ethnic
origin in South Africa. Am J Med Genet 52:279284.
Perel Y, Butendandt O, Carrere A, Saura R, Fayon M, Lamireau T, Vergnes
P. 1998. Oesophageal atresia, VACTERL association: Fanconis anaemia
related spectrum of anomalies. Arch Dis Child 78:375376.
Porteus MEM, Cross Y, Burn J. 1992. VACTERL with hydrocephalus: One
end of the Fanconi anemia spectrum of anomalies. Am J Med Genet
43:10321034.
Rossbach HC, Sutcliffe MJ, Haag MM, Grana NH, Rossi Ar, Barbosa JL.
1996. Fanconi anemia in brothers initially diagnosed with VACTERL
association with hydrocephalus, and subsequently with BallerGerold
syndrome. Am J Med Genet 61:6567.
Sasaki MS, Tonomura A. 1973. A high susceptibility of Fanconis anemia to
chromosome breakage by DNA crosslinking agents. Cancer Res
33:18291836.
Schroeder TM, Anschutz F, Knopp A. 1964. Spontaneous chromosome
aberrations in familial panmyelopathy. Hum Genet 1:194.