American Journal of Medical Genetics 87:434–435 (1999)
Apple-Peel Intestinal Atresia Associated With
Balanced Reciprocal Translocation
t(2;3)(q31.3;p24.2) mat
Kiyoshi Imaizumi,1* Junko Kimura,1 Mitsuo Masuno,1 Yoshikazu Kuroki,1 and Toshiji Nishi2
1
Division of Medical Genetics, Kanagawa Children’s Medical Center, Yokohama, Japan
2
Division of Surgery, Kanagawa Children’s Medical Center, Yokohama, Japan
Apple peel intestinal atresia is an apple-
peel-appearing bowel obstruction of un-
known cause. We describe a Japanese girl
with the apple-peel jejunal atresia associ-
ated with apparently balanced reciprocal
translocation between chromosomes 2 and
3, t(2;3)(q31.3;p24.2)mat. The translocation
breakpoints in the patient may become can-
didate regions for the putative gene causing
apple-peel atresia. Alternatively, the asso-
ciation of the two abnormalities in the pa-
tient is coincidental because her phenotypi-
cally normal mother had the same chromo-
some translocation. Am. J. Med. Genet.
87:434–435, 1999. © 1999 Wiley-Liss, Inc.
KEY WORDS: apple-peel jejunal atresia;
chromosome 2; chromosome 3
INTRODUCTION
Jejunal atresia is the most common cause of newborn
bowel obstruction, and it is classified into five types
according to its anatomic appearance [Martin and Zer-
ella, 1976]. Apple-peel type (Type IIIb, MIM 243600) is
often familial [Mishalany and Najjar, 1968; Farag et
al., 1993; Blyth and Dickson, 1969; Seashore et al.,
1987]. Although the cause of this condition remains
unknown, autosomal recessive inheritance has been
suggested as one of underlying mechanisms [McKu-
sick, 1999]. Here, we report on a patient with apple-
peel jejunal atresia and a balanced reciprocal translo-
cation, t(2;3)(q31.3;p24.2)mat. The possible role of
the translocation playing in the intestinal atresia is
discussed.
Contract grant sponsor: The Ministry of Health and Welfare of
Japan.
*Correspondence to: Kiyoshi Imaizumi, M.D., Division of Medi-
cal Genetics, Kanagawa Children’s Medical Center, Mutsukawa
2-138-4, Minami-ku, Yokohama 232-8555, Japan.
Received 1 April 1999; Accepted 27 July 1999
© 1999 Wiley-Liss, Inc.
CLINICAL REPORT
The girl was the first product of healthy and noncon-
sanguineous parents. At her birth, the mother was 31
and the father 35 years old. She was born at 36 weeks
of gestation after an uneventful pregnancy with a birth
weight of 2,186 g, length of 45.0 cm, and OFC of 32.0
cm. Family history was unremarkable. One day after
birth, she had bilious vomiting, and a radiograph with
barium showed a jejunal obstruction. Atresia of the je-
junum with intestinal malrotation was found, the ob-
structed jejunum having a coiled “apple peel” appear-
ance. The necrotic jejunal segment was excised and
end-to-end anastomosis between the proximal and dis-
tal jejunum was constructed, leaving 12 cm of viable
small bowel. Histopathological examination of the ex-
cised intestinal segment showed hemorrhagic necrosis.
Her postoperative course was poor, in part due to short
bowel syndrome. She was discharged by age 7 months.
Her somatic growth was poor, but she had no minor
anomalies or delayed psychomotor development.
GTG-banded chromosome analysis of peripheral
blood lymphocytes from the patient showed a
46,XX,t(2;3)(q31.3;p24.2) karyotype (Fig. 1). This find-
ing was confirmed by fluorescence in situ hybridiza-
tion (whole chromosome painting). High-resolution
chromosome analysis confirmed that there was no
visible deletion on the translocated chromosomes.
The karyotype of the mother was the same as that
of the patient, whereas her father had a normal 46,XY
karyotype.
DISCUSSION
“Apple peel” intestinal atresia may be heterogeneous
and may include the atresia/bowel malrotation as
single-gene defects, i.e., autosomal dominant or reces-
sive atresias [McKusick, 1999], or as polygenic disor-
ders. It occurs either as an isolated anomaly or as part
of clinical manifestations of genetic syndromes. In fact,
over 15% of reported patients with apple-peel atresia
had multiple congenital anomalies [Seashore et al.,
1987]. Our patient and her mother have an apparent
balanced reciprocal translocation, t(2;3)(q31.3;p24.2).
Several explanations are possible for the association of
the atresia with the translocation. If the atresia is an

Fig. 1. G-banded partial karyotype of the proband. Arrows show break-
points at 2q31.3 and at 3p24.4.
autosomal recessive trait and if the paternal allele in
the patient is considered to be mutated, the transloca-
tion might disrupt the maternal allele, leading to un-
masking of such a recessive gene. Second, the putative
disease gene might be paternally imprinted, and the
active maternal allele is disrupted by the translocation,
resulting in a functional nullizygous condition in the
patient, as suggested by Fukushima et al. [1993]. In
this case, the intact, active allele in the phenotypically
normal mother would have come from the grand-
mother. However, although maternal uniparental di-
somy for chromosome 2 has been reported in a baby
with growth failure, hypothyroidism, and hyaline
membrane disease [Harrison et al., 1995], no imprinted
genes have been identified on chromosomes 2 and 3
[Morison and Reeve, 1998]. Alternatively, because the
phenotypically normal mother has a translocation
Apple-Peel Intestinal Atresia 435
identical to that of the patient, the simultaneous occur-
rence of the atresia and translocation in the patient is
coincidental.
Numbers of genes have been assigned to 2q31-q32
and to 3p24.2. Among them, the HOXD1-HOXD13
gene complex, the integrin alpha-V subunit genes (IT-
GAV), and the postmeiotic segregation increased (S.
cerevisiae)-like 1 gene (PMS1), all at 2q31-q32, are of
potential interest because HOXD genes may play a role
in body axis determination [Krumlauf, 1994], liveborn
mice nullizygous for the mouse homolog (ItgaV) of IT-
GAV consistently exhibit intracerebral and intestinal
hemorrhages, and mutations in PMS1 was found in
colorectal cancers (hereditary nonpolyposis type 3)
[Nicolaides et al., 1994]. It remains to be seen whether
mutations of these genes are related to the apple-peel
anomaly. Mapping of the genes to the breakpoint and/
or cloning of the breakpoint DNA will clarify the
question.
REFERENCES
Bader BL, Rayburn H, Crowley D, Hynes RO. 1998. Extensive vasculogen-
esis, angiogenesis, and organogenesis precede lethality in mice lacking
all alpha-V integrins. Cell 95:507–519.
Blyth HM, Dickson JAS. 1969. Apple peel syndrome (congenital intestinal
atresia): a family study of seven index patients. J Med Genet 6:275–
277.
Farag TI, Al-Awadi SA, Ei-Badramany MH, Usher R, Ei-Ghanem M. 1993.
Second family with ‘apple peel’ syndrome affecting four siblings: auto-
somal recessive inheritance confirmed. Am J Med Genet 47:119–121.
Fukushima Y, Ohashi H, Wakui K, Fujiwara M, Nakamura Y, Ogata K.
1993. Polysplenia syndrome and paracentric inversion of chromosome
11 [46,XX, inv (11)(ql3q25)]. Am J Hum Genet 53:1543A.
Harrison K, Eisenger K, Anyane-Yeboa K, Brown S. 1995. Maternal uni-
parental disomy of chromosome 2 in a baby with trisomy 2 mosaicism
in amniotic fluid culture. Am J Med Genet 58:147–151.
Krumlauf R. 1994. Hox genes in vertebrate development. Cell 78:191–201.
Martin LW, Zerella JT. 1976. Jejunal atresia: a proposed classification. J
Pediatr 11:399–403.
Mishalany HG, Najjar FB. 1968. Familial jejunal atresia: three cases in
one family. J Pediatr 73:753–755.
Morison IM, Reeve AE. 1998. A catalogue of imprinted genes and parent-
of-origin effects in human and animals. Hum Mol Genet 7:1599–1609.
Nicolaides NC, Papadopoulos N, Liu B, Wei Y-F, Carter KC, Ruben SM,
Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM, Adams MD,
Venter JC, Dunlop MG, Hamilton SR, Petersen GM, de la Chapelle A,
Vogelstein B, Kinzler KW. 1994. Mutations of two PMS homologues in
hereditary nonpolyposis colon cancer. Nature 371:75–80.
Seashore JH, Collins FS, Markowitz RI, Seashore MR. 1987. Familial
apple peel jejunal atresiac: surgical, genetic, and radiographic aspects.
Pediatrics 80:540–544.