Double trisomy with 48, XXX+21 karyotype in a Down's syndrome child from Jammu and Kashmir, India

Abstract

An 11-day-old female child, the third in birth order of a nonconsanguineous
couple, was found to have a double trisomy
(48, XXX+21) upon karyotyping. The proband has the typical
Down’s syndrome phenotype and the same was attributed
to trisomy-21.
The occurrence of double aneuploidy is a relatively
rare phenomenon in human (MacFaul et al. 1981; Cyrus et
al. 2005). Most reported cases of double aneuploidy are
presented in the form of spontaneous abortions. The reported
cases involving autosome and/or sex chromosome
aneuploidy, such as double autosomal trisomy and autosomal
trisomy with sex chromosome monosomy or trisomy,
are extremely rare in live newborns (MacFaul et al. 1981;
Reddy 1997). The patient with double aneuploidy may have
manifestations of both chromosomal abnormalities

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c
Indian Academy of Sciences
RESEARCH NOTE
Double trisomy with 48, XXX+21 karyotype in a Down’s syndrome child
from Jammu and Kashmir, India
WAHIED KHAWAR BALWAN, PARVINDER KUMAR, T. R. RAINA and SUBASH GUPTA*
Human Genetic Research cum Counselling Centre, University of Jammu, Government Medical College,
Jammu 180 006, India
Introduction
An 11-day-old female child, the thirdin birth order of a non-
consanguineous couple, was found to have a double trisomy
(48, XXX+21) upon karyotyping. The proband has the typi-
cal Down’s syndrome phenotype and the same was attributed
to trisomy-21.
The occurrence of double aneuploidy is a relatively
rare phenomenon in human (MacFaul et al. 1981; Cyrus et
al. 2005). Most reported cases of double aneuploidy are
presented in the form of spontaneous abortions. The re-
ported cases involving autosome and/or sex chromosome
aneuploidy, such as double autosomal trisomy and autoso-
mal trisomy with sex chromosome monosomy or trisomy,
are extremely rare in live newborns (MacFaul et al. 1981;
Reddy 1997). The patient with double aneuploidy may have
manifestations of both chromosomal abnormalities. Dou-
ble aneuploidy that leads to trisomy and/or monosmy of
the two different chromosomes arises because of two mei-
otic nondisjunctional events (Lorda-Sanchez et al. 1991;
Park et al. 1995; Cyrus et al. 2005). However, in hu-
man, monosomy of chromosomes other than sex chrmo-
somes is virtually nonexistent, presumably due to incom-
patibility of autosomal monosomies at an early stage of
gestation (Hassold and Jacobs 1984). However, trisomy
is the most commonly identified chromosomal abnormal-
ity in humans occurring in at least 4% of all clinically
recognised pregnancies (Hassold and Jacobs 1984). The
vast majority of trisomies are associated with a single ad-
ditional chromosome, although two other types of trisomic
conceptions are occasionally observed, namely, those with
two additional chromosomes or double trisomies, and those
with either normal and trisomic-cell lines or mosaic tri-
somies (Hassold and Jacobs 1984). Double trisomy i.e., +21
*For correspondence. E-mail: drsubashgupta13@rediffmail.com.
and triple-X could have a same or different parental origin
(Park et al. 1995; Cyrus et al. 2005). The coincidence rate of
both trisomy-21 and triple-X in the same individual is very
low as compared to trisomy-21 (Papp et al. 1977; Verma et
al. 1979; Cyrus et al. 2005). Trisomy-21 and triple-X in the
same individual have been reported earlier (Breg et al. 1962;
Upadhyaya and Verma 1975; Papp et al. 1977; Verma et al.
1979; Park et al. 1995; Devlin and Morrison 2004). Present
report of double trisomy in a clinical Down’s syndrome case
is an addition to the existing literature.
Case history
An 11-day-old female infant with a clinical symptoms of
Down’s syndrome (figure 1) was taken up for chromosome
study. She was third in birth order of a nonconsanguineous
couple. At the time of the child’s birth the mother was 35
years old and father was 37 years old. The proband was
born 10 years after the second child. The proband had mon-
goloid face, flat nasal bridge, smaller mid-phalynx of short
finger, unilateral simian crease on right palm, thick furrowed
tongue, low set ears, open mouth and gap between the first
and second toes.
Cytogenetic study
Chromosomal study carried on the proband showed 48
chromosomes in every well-spread G-banded metaphase
plate. Some of these G-band metaphase plates were kary-
otyped. Every karyotype thus prepared showed two trisomies
viz. trisomy-21 and triple-X (figure 2).
Discussion
A rare case of double chromosome aneuploidy including
Down’s syndrome (trisomy-21) and triple-X was described.
Keywords. human karyotyping; Down’s syndrome; triple-X; double trisomy.
Journal of Genetics, Vol. 87, No. 3, December 2008 257

Wahied Khawar Balwan et al.
Figure 1. Phenotype of the proband.
The proband had features typical of Down’s syndrome and
chromosome study showed 48, XXX+21 karyotypes i.e. the
child had double trisomy. Study of the existing literature
shows the rate of both Down’s syndrome and triple-X in
the same individual to be far lower than trisomy 21 alone.
Double trisomy involving X-chromosome and chromosome
number 21 have earlier been reported by Papp et al. (1977),
Verma et al. (1979), Park et al. (1995) and Devlin and Mor-
rison (2004), and our findings in the proband are similar to
the previous reports and an addition to the existing literature.
Most cases of double aneuploidies in liveborns involve
the sex chromosomes combined with trisomy 13, 18 or 21
(Hou and Wang 1996). Both aneuploidies arise as a result of
nondisjunction in maternal meiosis II (Park et al. 1995) and
these results support the hypothesis that a segregation defect
at the cellular level may cause nondisjunction involving more
than one chromosome. The present case is an isolated one
in the family, as she is the third in birth order and both the
first two offspring of the couple are normal. The additional
X chromosome may have come from either the maternal or
Figure 2. Chromosome complement (2n=48) and karyotype (48, XXX+21) of
the proband.
258 Journal of Genetics, Vol. 87, No. 3, December 2008

Double trisomy and Down’s syndrome
paternal side. However, trisomy-21 has typically been cor-
related with the advanced maternal age (Verma et al. 1979;
Kothare et al. 2002). In the present study, the maternal age is
35 years and is likely a cause of the nondisjunction of chro-
mosome number 21.
The present case, and most of the published reports on
48, XXX+21, have shown features typical of Down’s syn-
drome alone (Verma et al. 1979; Papp et al. 1977; Park et
al. 1995). Further reports of double aneuploidy of trisomy-
21 and triple-X highlighting the clinical characteristics will
aid in a better understanding of the phenotype–genotype
relationship.
Acknowledgements
Authors are thankful to Jammu and Kashmir State Council, Science
and Technology, for providing financial support.
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Received 8 February 2008, in revised form 18 March 2008; accepted 28 April 2008
Published on the Web: 29 August 2008
Journal of Genetics, Vol. 87, No. 3, December 2008 259