REPORT OF A NEW CASE WITH PENTASOMY X
AND NOVEL CLINICAL FINDINGS
Demirhan O, Tanriverdi N, Yilmaz MB, Kocaturk-Sel S,
Inandiklioglu N, Luleyap U, Akbal E, Comertpay G,Tufan T, Dur O
*Corresponding Author: Professor Dr. Osman Demirhan, Department of Medical Biology and Genetics, Faculty
of Medicine, Çukurova University, 01330 Saricam, Adana, Turkey. Tel: +90-322-338-7140. Fax: +90-322-
338-6572. E-mail: osdemir@cu.edu.tr
page: 85
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DISCUSSION
Pentasomy X is a rare chromosomal abnormality
with an unknown prevalence, and has been associated
with severe clinical conditions. Pentasomy X
syndrome was first reported by Kesaree and Wooley
in 1963 [1]. These patients usually have normal
genitalia, but secondary sex characteristics can be
incomplete. Pentasomy X syndrome has been associated
with severe clinical conditions, presumably
resulting from failure or disruption of X chromosome
inactivation [7]. No adults with pentasomy X have
been reported since the prognosis is universally poor.
Here, we describe a case of 49,XXXXX karyotype
in a 1-year-old girl. The principal features of the
pentasomy X syndrome are set out in Table 1 and
illustrated in Figure 1.
Pentasomy X chromosomes result sporadically
from either meiotic non disjunction, where a chromosome
fails to separate during the first or second
division of gametogenesis, or from mitotic non disjunction
in the developing zygote. If by chance the X
chromosomes do not separate properly and they go
on to the next cell division and again do not divide
properly, when the sperm fertilizes the egg the fetus
can then end up with four X chromosomes and one
X (49,XXXXX). Just as in our study, all the chromosome
X-specific STR markers of the case were
inherited from the mother (origin of the aneuploidy
is maternal) and heterozygosity was retained in all regions
(proximal, medial and distal regions) of the four
chromosomes. This is the expected conditions of non
disjunction in both meiosis I and meiosis II. Some
researchers indicate that molecular genetic analyses
using polymorphic DNA markers have enabled the
study of non disjunction of fetal aneuploidy as well as
determination of parental origin and cell stage errors
at meiosis I or II [3,5,6].
In the present study, the most important prognostic
feature consists of extreme thenar atrophy,
hypotonia, micrognathia and cardiovascular anomalies
(Figure 1). Some of these clinical manifestations
were consistent with those described previously in
patients with pentasomy X, except for thenar atrophy.
The hands and feet are generally small and camptodactyly,
clinodactyly, and radioulnar synostosis are
common findings in the pentasomy X syndrome.
In addition to these hand findings, we report the
first case with extreme thenar atrophy, which was
not found in previous cases. A karyotype is therefore
mandatory in infants with moderate-to-severe
thenar atrophy, in order to exclude polyploidy X
chromosome. Girls with a pentasomy X generally
have mental retardation, mongoloid face, short neck,
simian crease, clinodactyly of the fifth finger and
congenital heart disease [7]. Because most patients
with pentasomy X syndrome (including ours) have
developmental delay, postnatal growth deficiency,
epicanthus and a mongoloid slant of facial anomalies
and hypotonia, similar to the abnormalities seen in
Down’s syndrome, occasional diagnostic problems
have also been reported [8] (Figure 1). Because patients
can be misdiagnosed as having Down’s syndrome,
the correct diagnosis requires cytogenetic
analysis.
The patients with pentasomy X syndrome have a
poor prognosis due to severe cardiac failure and infectious
diseases [2,9-12]. Immunoglobulin anomalies
and an increased susceptibility to infection have also
previously been reported in patients with pentasomy
X. Immunoglobulin values in our case had not been
tested. However, history of a greatly increased incidence
of recurrent infections and fever was found in
our case, whereas Boeck et al. [13] described their patient
as having a lifelong history of eczema, recurrent
pneumonia and staphylococcal abscess. Pneumonia
development from early infancy, as seen in our case,
has also been described in this syndrome. The normal
external genitalia seen in our case have been reported
in previous patients, although gonadal dysfunction
has been seen in many cases, including a postmortem
case [1,14-16]. These findings suggest that despite the
normal appearance of the external genitalia, there is
an underlying gonadal dysfunction in patients with
pentasomy X syndrome. Because our case was an
infant, her sexual development and bone maturation
remain to be assessed. Growth deficiency was evident
in the majority of affected children at the time of birth.
Birth weight of our case was unknown. However,
she was born by Cesarean section during the 32nd gestational week as a result of premature membrane
rupture, and had postnatal growth deficiency and developmental
delay; these anomalies have also been
described in this syndrome. Her intellectual functions
had not been formally tested, but were suspected to
be at low-average.
Patients with pentasomy X syndrome generally
have congenital heart defects; usually patent
ductus arteriosus or a ventricular septum defect
[1,8,9,11,12,14,16]. Just as documented, cardiac
defects were present in nine (45.0%) of 20 children
with 49,XXXXX (Table 1). Our case had a surgical
operation for cardiac murmurs and patent ductus arteriosus.
Reports in the medical literature agree that
around 50.0% of girls are born with a heart condition.
However, the medical literature includes girls
with an innocent heart murmur. The most common
defects are holes between the lower chambers of the
heart and a condition called persistent ductus arteriosus
that is left-over from the way the circulation
operates during fetal life. Some cases are born with
a more complex heart condition and will need a surgical
operation. Three of those children developed
congestive heart failure within the first year of life
and required surgical ligation of the ductus. A karyotype
is therefore mandatory in female newborns with
moderate-to-severe hypotonia (including our case),
in order to exclude polyploid mosaicism of the X
chromosome [17]. Genetic counseling is indicated
during subsequent pregnancies. Parents must realize
that, apart from somatic areas being affected (facial
dysmorphism, skeletal, cardiovascular and gonadal
systems), all major areas of development will be
affected by the addition of extra X chromosomes.
However, an overall prognosis seems impossible due
to a substantial variability within all polysomy X
groups. In addition, the other structural abnormalities,
del(13)(q22-p2) and chtbr(3q), were observed in two
cells of our case (Figure 2). This loss of chromosome
and chromatid break may affect susceptibility to the
progression of the disease.
In conclusion, the clinical manifestations observed
in our case were consistent with those described
previously in patients with pentasomy X.
To the best of our knowledge, we are the first to
report thenar atrophy in a case with 49,XXXXX.
Chromosome karyotyping is generally required in
the presence of facial dysmorphism or other somatic
abnormalities, to exclude underlying sex chromosomal
aneuploidy disorder, such as the 49,XXXXX
syndrome. Additional studies about polyploidies
are needed to determine the nature of the errors in
such cases. Evaluation of exceptional instances of
segregation failure may be useful in improving our
understanding of the general mechanisms of non disjunction.
Molecular techniques could be useful for
the pre and postnatal diagnosis of the common aneuploidies
and determining its parental origin. These
kinds of studies will improve our knowledge about
the mechanisms of aneuploidies, and enable appropriate
and prompt genetic counseling.
Declaration of Interest. The authors report no
conflicts of interest. The authors alone are responsible
for the content and writing of this article.
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