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Partial trisomy of chromosome 15q and partial monopsony of 6q due to maternal balanced translocation
J Pediatr Neurosci. 2014 May-Aug; 9(2): 178–181.
PMCID: PMC4166849
doi: 10.4103/1817-1745.139354
Partial trisomy of chromosome 15q and partial monopsony of 6q due to maternal
balanced translocation
Shilpy Singla, Kausik Mandal, 1 Suvasini Sharma, and Viswas Chhapola
Department of Pediatrics, Lady Hardinge Medical College and Associated Kalaw ati Saran Children's Hospital, New Delhi, India
1
Department of Medical Genetics, Medical Genetics, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow , Uttar Pradesh, India
Address for correspondence: Dr. Suvasini Sharma, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalaw ati Saran
Children's Hospital, New Delhi, India. E-mail: [email protected]
Copyright : © Journal of Pediatric Neurosciences
This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, w hich
permits unrestricted use, distribution, and reproduction in any medium, provided the original w ork is properly cited.
Abstract
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A 7-month-old male presented with developmental delay and multiple congenital anomalies. He was found to have partial
trisomy for the distal segment of chromosome 15 (q22-qter). Chromosome analysis of the mother showed a reciprocal
balanced translocation between long arms of chromosome 6 and 15, t (6;15)(q26;q22).
Keywords: Congenital anomalies, partial trisomy 15q, translocation 6;15
Introduction
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Partial trisomy of chromosome 15 was first reported by Fujimoto et al. in 1974.[1] Since then, over 20 such cases have
been reported in the medical literature.[2] Most of the cases involved distal segment of chromosome 15, with the
breakpoints at q22 or distal to it.[3,4] We report a case of a 7-month-old male with partial trisomy 15 due to balanced
translocation involving chromosomes 6 and 15 in the mother.
Case Report
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A 7-month-old male was brought with developmental delay. He was born to nonconsanguineous parents, mother aged
36 years and father aged 38 years, with three normal elder daughters. The fourth baby was a male, who died 6 h after
birth. He had dysmorphism, and the parents were told that the baby had some genetic disorder. However, no
documentation of dysmorphic features or karyotype was available. The fifth pregnancy, 1-year later, was a spontaneous
abortion at 3 months gestation.
The proband was conceived as the sixth pregnancy. The family came to medical attention at 23 weeks 3 days of
pregnancy when an ultrasound had detected bilateral club feet, thickened nuchal skin fold, cerebral ventriculomegaly,
hypoplastic cerebellum, unilateral right renal pelviectasis. The findings suggested chromosomal anomaly and
amniocentesis was done for fluorescent in-situ hybridization for chromosome 21 and karyotype analysis. The fluorescent
in-situ hybridization for chromosome 21 showed two signals in each cell. Karyotype showed an “extra genetic material”
on a long arm of chromosome 6 [Figure 1]. The parents were counseled about the risk of mental retardation in the baby
and were advised to undergo chromosomal analysis. They, however, decided to continue the pregnancy in view of
advanced gestational age.
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Partial trisomy of chromosome 15q and partial monopsony of 6q due to maternal balanced translocation
Figure 1
Karyotype of the baby (prenatal sample) showing an extra chromosomal material on chromosome 6
At term, the mother went into labor. Fetal distress was detected in the form of fetal bradycardia and meconium stained
liquor. The baby was delivered by a lower segment cesarian section. He cried immediately at birth. He developed fast
breathing and received oxygen and intravenous fluids. He improved gradually and was discharged after 6 days. There
was no history of seizures, encephalopathy, or jaundice in the neonatal period.
He developed social smile at 3 months, and was recognizing his mother and reaching out for objects at the time of
presentation. He had achieved partial neck holding. Vision and hearing were normal. There was no history of seizures.
On examination, the infant had an abnormal posture with his legs in abducted and flexed position. He weighed 7.5 kg
(<25th centile for age), measuring 72.5 cm in crown-heel length (>75th centile for age). The child had microcephaly
(head circumference of 40 cm, <−3 standard deviation). He had facial asymmetry, strabismus involving the left eye,
narrow down-slanting palpebral fissures, prominent nose, overhanging columella, long philtrum, small pointed chin,
midline crease in the lower lip and high arched palate [Figure 2]. He also had club feet, and long tapering fingers, with
middle finger being overlapped by other fingers. The neurological and systemic examination was normal.
Figure 2
(a) Facial asymmetry, strabismus involving the left eye, narrow down-slanting
palpebral fissures, prominent nose, overhanging columella, long philtrum, small
pointed chin, midline crease in the lower lip. (b) Long and tapering fingers, with
middle finger ...
Investigations revealed a normal hemogram, liver, and kidney function tests. Ultrasonographical evaluation of the
abdomen revealed no abnormality. Magnetic resonance imaging of the brain revealed mild thinning of the corpus callosum
without any other abnormalities. Echocardiography was normal.
Karyotype analyses of parents were carried out in view of previous sibling death with dysmorphism and history of
spontaneous abortion in mother. Father's karyotype was normal. Karyotype of the mother revealed a balanced
translocation between chromosomes 6 and 15; t (6;15)(q26;q22) [Figure 3].
Figure 3
Karyotype of the mother showing a balanced translocation between
chromosomes 6 and 15; t(6;15)(q26;q22)
From the above dysmorphic features, physical findings and the patient's and his mother's karyotype, a diagnosis of partial
trisomy of chromosome 15 (q22 → qter) due to balanced translocation in the mother was made. As the child inherited
the derivative chromosome 6 from the mother, it was clear that, he also had terminal deletion of 6q (q26 and q27). The
child was started on physical and occupational therapy.
Genetic counseling was provided to the family. The family was able to understand that the anomalies and developmental
delay are due to the chromosomal imbalances in the affected child. They also were able to understand that the
chromosomal anomaly in this child and probably some of the previous pregnancy losses are related to the balanced
translocation in one of the parents. The recurrence risk and availability of prenatal testing early in pregnancy has been
explained. Other reproductive options like use of a donor ovum have also been discussed. The importance of extended
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Partial trisomy of chromosome 15q and partial monopsony of 6q due to maternal balanced translocation
family screening for the same balanced translocation on the mother's side; and its importance for the prevention of
recurrences in the extended family has been explained.
Discussion
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The karyotype of our patient contained an extra genetic material on a long arm of chromosome 6 (46, XY, 6q+).
Chromosomal analysis of the parents showed the mother to be a balanced translocation carrier, with the karyotype 46,
XX, t (6;15)(q26;q22). The extra genetic material was thus found to be a segment of chromosome 15, which was
attached to the long arm of chromosome 6 in the proband. The congenital anomalies and the global developmental delay
in our case were thus, due to a partial distal trisomy of chromosome 15. Partial distal trisomy of chromosome 15, in some
cases, has been reported to be due to a balanced translocation in one of the parents.
The range and severity of symptoms and physical findings may vary from case to case, depending upon the length and
location of the duplicated portion of chromosome 15 and the second chromosome involved in the translocation.[3,4]
Even though the breakpoint in the second chromosome is often in the terminal region, modifying effects of an
undetectable deletion or duplication of genetic material involving the second chromosome may still occur. As is evident
from the clinical profile, all the cases reported until date, the phenotype due to a partial distal trisomy of chromosome 15
is clinically distinguishable. It is usually characterized by a delay in language development and motor skills such as walking
or sitting up, growth and mental retardation. Distinctive craniofacial features may include microcephaly, antimongoloid
slant, epicanthal folds, micrognathia, flattened nasal bridge, long philtrum, puffy cheeks and high arched palate.[4,5,6,7]
Other abnormalities may include hypotonia, seizures, skeletal deformities and abnormal fingers and toes.
Cardiomyopathy, renal anomalies or abnormal genitalia may also be found.[6,7]
Our patient had microcephaly, micrognathia, long philtrum and high arched palate, which was consistent with the physical
appearance described in this anomaly. Also, our patient had strabismus and flexion deformities of fingers and toes, which
have been reported in very few patients with this disorder.[8] The second chromosome involved in our case is
chromosome 6 and some features like ventriculomegaly and hypoplasia of corpus callosum, might be contributed by the
terminal monosomy of chromosome 6.[9,10] Our case thus helps in expanding the spectrum of partial trisomy 15. Unlike
our case, there can be translocations leading to smaller imbalances in the offspring. Prenatal karyotype by Giemsa
banding might miss such small imbalances, which might have unfavorable consequences. Multiplex ligation-dependent
probe amplification, fluorescence in-situ hybridization or cytogenetic microarray may be used as an adjunct diagnostic
technique to look for small cryptic imbalances in the fetus. Importance of detection of such chromosomal anomalies lies in
the fact that the family can be provided genetic counseling so that the family can adapt to the problem and also take a
decision regarding future pregnancies. As mother is a carrier of balanced translocation; she is likely to produce gametes
with chromosomal imbalance during meiosis. The overall chance of having normal children is around 60-70%. The
private risk for the balanced translocation described by us is not available. Prenatal testing early in pregnancy by
chromosomal analysis from chorionic villus sample (9-11 weeks) or amniotic fluid (15-16 weeks) or by ultrasonography
to look for associated physical anomalies as described in the affected child, are viable methods to prevent recurrences.
Footnotes
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Source of Support: Nil
Conflict of Interest: None declared.
References
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2. Scarbrough PR, Howard-Peebles PN, Finley WH, Finley SC. Complex chromosome rearrangement resulting in
trisomy l5q22-15qter. Am J Hum Genet. 1981;33:119.
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Partial trisomy of chromosome 15q and partial monopsony of 6q due to maternal balanced translocation
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9. Gerber JC, Neuhann TM, Tyshchenko N, Smitka M, Hackmann K. Expanding the clinical and neuroradiological
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10. Chen CP, Chen YY, Chern SR, Wu PS, Su JW, Chen YT, et al. Prenatal diagnosis and molecular cytogenetic
characterization of de novo partial trisomy 12q (12q24.21 → qter) and partial monosomy 6q (6q27 → qter) associated
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Articles from Journal of Pediatric Neurosciences are provided here courtesy of M e dknow Publications
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