Chromosomal abnormalities - A review

Shubhangi Khandekar, Alka Dive, Prashant Munde

Abstract
With the discovery in 1956 that the correct chromosome number in humans is 46, the new era of clinical
cytogenetics began its rapid growth. During the next few years, several major chromosomal
syndromes with altered numbers of chromosomes were reported, i.e. Downsyndrome (trisomy21),
turner syndrome (45,x) and klinefelter syndrome (47,xxy). Since then it has been well established that
chromosome abnormalities contribute significantly to genetic disease resulting in reproductive loss,
infertility, stillbirths, congenital anomalies, abnormal sexual developmentmental retardation and
pathogenesis of malignancy.specific chromosome abnormalities have been associated with over 60
identifiable syndromes. They are present in at least 50% of spontaneous abortions, 6% of stillbirths,
about 5% of couples with two or more miscarriages and approximately 0.5% of newborns. In women
aged 35 or over, chromosome abnormalities are detected in about 2% of all pregnancies. Some of the
abnormalities and their clinical consequences will be Discussed in the following sections.
Key Words: Chromosomal abnormalities, numerical, structural abnormalities, syndromes.

Introduction Chromosomal abnormalities may also be

A chromosomal disorder occurs when there is a
change in the number or structure of the
chromosomes. This change in the amount or
arrangement of, the genetic information in the
cells may result in problems in growth,
development and/or functioning of the body
systems1. The chromosomal abnormalities may
occur either during the production of the egg or
sperm or early after the baby's conception: a
spontaneous occurrence for unknown reasons2,3.
Address for Correspondence
Dr. Shubhangi Khandekar
Professor,
Department of Oral Pathology & Microbiology,
VSPM Dental College & Research Centre,
Nagpur – 440019. Mob. : + 91 8149336195
E-mail : pinkclimate@gmail.com
inherited from a parent.
There are two main types of chromosomal
disorders: changes in chromosome number and
changes in chromosome structure
Chromosomal disorders
Major category of human disease, represent 1%
of live births, 2% of pregnancies in women older
than 35, 50% of all spontaneous first trimester
abortions, responsible for more than 100 human
syndromes and are more common than all
Mendelian single-gene disorders5.
Chromosomal abnormalities
sometimes also called cytogenetic disorders –
are very common. Most fetuses with some
chromosomal abnormality usually do not
survive. About 50% of first–trimester abortions

35 Central India Journal of Dental Sciences, Vol. 4 (1), Jan - Mar 2013
are connected with some cytogenetic mistake.
The incidence of chromosomal abnormalities is
approximately 1 out of 200 of newborns1.
We are able to find the disorders due to
karyotype testing. The cytogeneticists get the
samples (blood, amnionic fluid), then stain the
chromosomes and arrange them in the right
order by their length. Then we can see some
changes in pattern (banding). The most typical
method is giemsa stain, so it is usually called "g
banding". This is important for structural
abnormalities. Numeral abnormalities we can
identify even easier6, 7.
Other classification of chromosomal
abnormalities depends on fact which type of
chromosome is affected – autosomes (down
syndrome, digeorge syndrome) or sex
chromosomes (klinefelter syndrome, turner
syndrome).
Etiology of chromosome abnormalities
Etiology of chromosome abnormalities is pretty
variable. The most often reason is mistake which
occurs during the cell division. It is connected
with wrong development of the sperm or ovum
(female reproduction cell)4.
There are two types of cell division – mitosis
and meiosis. Other causes are the maternal age
and the influence of the environmental.
Chromosome abnormalities are usually fatal.
Each second first-trimester abortion is caused
by them. Children who survive and get born
suffer from very serious mental and physical
problems5. The screening for chromosome
abnormalities is very important. The
cytogeneticists use the karyotype testing6.
Problems in the cell division
There are two main types of the cell division.
The first one is the meiosis. It is the process of
division of reproduction cells. The result is a cell
with 23 chromosomes (it is haploid). Fetus gets
36 Central India Journal of Dental Sciences, Vol. 4 (1), Jan - Mar 2013
23 chromosomes from the mother and 23
chromosomes from the father. Cells of fetus are
already diploid (2n). Mistake during meiosis
leads to incorrect number of the chromosomes
in the egg or in the sperm5. Child can get some
extra chromosome (trisomy) or miss it
(monosomy).
The second type of cell division is the mitosis. It
occurs in all non-reproductive cells. It is a form
of duplication of the genetic information,
followed by the halving of material. The parent
cell has 92 chromosomes (4n), two subsidiary
cells have 46 Chromosome each (2n).Mitosis
starts immediately after fertilization and
continues throughout whole life6,7. When
mistake occurs, the chromosomes may not be
equal. Problems in mitosis lead to the mosaicism
more often.
Parent Cell Parent Cell
(2N) (2N)
Daughter Cell
(2N)
Daughter
Cell (N)
Mitosis Meiosis
Fig. 1 - Problems in the cell division
Age of parents
There is strong influence of the maternal age
(especially in Down syndrome). The paternal
age is less important, but still has its importance.
The difference is in cell division of reproduction
cells1. The number of eggs (female´s cells) is
done by our birth. So eggs underway meiosis
many times. The later age of delivery means the
higher risk of some abnormalities. It takes just 72
hours to the development of sperm cells. It is less
probably to make a mistake during this period3.
To the older women is recommended to visit
some genetic counseling centre. "The older
women" means more than 35 years. The
prenatal diagnosis is the best way to find some
affected children. The method of prenatal
diagnosis as an amniocentesis5.
Fig. 2 - Relation between maternal age &
development abnormalities
Influence of the environment
It is very hard to tell how important the
environmental is. We can´t find any significant
differences between parents with child with a
chromosome abnormality and parents with
healthy child. They have usually very similar
lifestyle or habits.5 But there are still some
dangerous influences – x-rays, medication or
food. Most of them have a cumulative character.
Because we are not sure about the origin of
abnormalities, it is hard to recommend any
prevention. Sometimes it is said that the folic
acid has a positive role in prevention of
congenital abnormalities. Pregnant women
should also get vitamins to reduce risks7.
Types of structural abnormalities
Translocation
During translocation, a part of one chromosome
is transferred to another chromosome. It is very
important whether the translocation is balanced
or unbalanced. Balanced means that two
chromosomes just exchange their parts but the
37
number of chromosomes (46 chromosomes) as
well as no loss of genetic material stays the
same2,3.
Fortunately – typical place of break is near the
centromere, usually only small arms of the
acrocentric chromosomes are lost. There are no
crucially important genes coded by these
chromosomal segments. So, a carrier of such
robertsonian translocation can normally
survive this cytogenetic change.
Unfortunately problems occur during the
fertilization with a gamete of a carrier of a
balanced translocation. Carrier of the
translocation may produce unbalanced zygotes,
because the process of homologous
chromosomes pairing during meiosis is
interrupted. This is very important because
unbalanced gametes lead to abnormalities in
offspring. The reason is that the offspring
receives altered chromosome from the carrier
which may lack several important genes6.
Therefore the only clinical symptom found in
the carriers of balanced translocations may be
the reproduction failure.
Karyotype
44,XY
Balanced trans location
Chromosomal breaks
Karyotype
Chromosome 44,XY
is too small
Robertsonian trans location
Fig. 3 - Translocation
Central India Journal of Dental Sciences, Vol. 4 (1), Jan - Mar 2013
Types of translocation
Reciprocal – translocation between two
chromosomes ("a segment" goes to "b
chromosome" and "b segment" goes to "a
chromosome")
Robertsonian – translocation (or fusion) of two
acrocentric chromosomes
Segment
Chromosome
Aberration
Chromosomal breaks
Fig. 4 - Robertsonian translocation
Deletion
Deletion is characterized by the loss of a part of
chromosome. Two breaks have to occur for
deletion of the interstitial segment. For deletion
of terminal segment (telomere) one break is
enough. Segments which were deleted from the
chromosome are not able to "live" on their own
and the genes present in those segments are lost.
One special example of deletion exists. It is
called "ring chromosome". It is a situation when
chromosome lost both of its ends. The long and
the small arms then connect together and
chromosome became a ring shaped.
Chromosome Ring chromosome
Segment
Ends of chromosome
Fig. 5 - Ring chromosome
38
Isochromosomes
Isochromosomes are created by the incorrect
division of centromere. Normally centromere
divides vertically. In this case it divides
horizontally.
The result is usually the loss of one arm. It means
that newly created chromosome has just two
long arms or two short arms which are normally
connected by centromere. It occurs relatively
frequently in X chromosome. It is a huge
problem during the fertilization. Because fetus
then becomes trisomic for one arm and
monosomic for the second arm.
Two long arm
Short arm
Two short arm
Centromore
Horizontal
Division
Long arm
Isochromosome
Fig. 6 - Isochromosome
Inversion
For inversion are typical two breakages in the
different part of the chromosome. The newly
created segments then replace each other.
Inversion was discovered in 1921. Although we
still don´t know why inversion exists, we know
that it is the most important mechanism of
reorganizing of the genome.
There are 2 types of inversion:
Pericentric – causing deletions, insertions or
abnormal centromere;
Paracentric – more common type, it is less
harmful for its carrier.
Inversion suppresses the recombination
process.
Central India Journal of Dental Sciences, Vol. 4 (1), Jan - Mar 2013
Parts of a chromosome
When we want to describe the location of some
structural abnormality we used special marks.
We have to count the regions always from the
centromere – for both arms. Example: 1q13
The first number is a number of chromosome –
chromosome 1;
(p) and (q) are used for marking of arm – (p) for
small arm and (q) for long arm – the long arm;
The third number is for the region of
chromosome – region 1;
Chromosomal marking last number is for the
band – band 3. So the change is located on the
long arm of chromosome 1
Abnormalities in chromosomal
number
Nondisjunction - Mistake in cell division where
chromosomes do not separate properly in
anaphase.Usually in meiosis, although in
mitosis occasionally. In meiosis, can occur in
anaphase I or II.
Polyploidy – complete extra sets (3n, etc.) – fatal
in humans, most animals.Aneuploidy – missing
one copy or have an extra copy of a single
chromosome. Three copies of a chromosome in
your somatic cells: TRISOMY. One copy of a
chromosome in your somatic cells: Monosomy
Most trisomies and monosomies are lethal well
before birth in humans; exceptions covered
below. Generally, autosomal aneuploids tend to
be spontaneously aborted. Over 1/5 of human
pregnancies are lost spontaneously after
implantation.Chromosomal abnormalities are
the leading known cause of pregnancy loss.
Data indicate that minimum 10-15% of
conceptions have a chromosomal abnormality.
At least 95% of these conceptions spontaneously
abort (often without being noticed)
39 Central India Journal of Dental Sciences, Vol. 4 (1), Jan - Mar 2013
Aneuploidy in human
sex chromosomes
X_ female (Turner Syndrome)
Short stature; sterile (immature sex organs);
often reduced mental abilities. About 1 in 2500
human female births
XXY male (Klinefelter syndrome)
Often not detected until puberty, when female
body characteristics develop. Sterile; sometimes
reduced mental abilities; testosterone shots can
be used as a partial treatment; About 1 in 500
human male births.
XYY male (XYY syndrome)
Usually tall, with heavy acne; some correlation
with mild mental retardation and with
aggressiveness; usually still fertile. About 1 in
1000 human male births
XXX female (triple X syndrome)
Usually just like XX females, except for having 2
Barr bodies in somatic cells. HOWEVER, more
likely to be sterile, and if fertile, more likely to
have XXY and XXX children. About 1 in 1000
human female births. Aneuploidy in human
autosomes
Autosomic monosomy
appears to be invariably fatal, usually very early
in pregnancy. Most autosomic trisomy is fatal,
but sometimes individuals trisomic for
autosomes 13, 15, 18, 21, or 22 survive to birth
and even beyond. Chromosome number reflects
size; bigger number = smaller size, and usually
fewer genes. Extra 13, 15, or 18 lead to multiple
defects and usually death well before 1 year of
age. Extra 22 is much like extra 21 (Down
syndrome, covered below), but usually more
severe, with shorter life expectancy.
 Trisomy 21 (Down syndrome)
The only autosomal trisomy condition in
humans that allows an appreciable number of
individuals to survive to adulthood Found in
about 1 in 750 live births.
A phenotypic ally identical condition occurs
that is not due to a true trisomy (it involves a
chromosomal translocation, covered later)
Traits include abnormal facial appearance, high
likelihood of mental retardation (degree varies
considerably), and increased likelihood of
developing leukemia and Alzheimer's disease
Likelihood of a child being born with Down
syndrome increases with the age of the mother
rate is as high as 1 in 16 live births for mothers
age 45 and over at conception. Not completely
clear why the odds go up so dramatically, likely
a combination of factors. It is clear that
Nondisjunction is more common in eggs than
sperm.Appears that spontaneous rejection of
aneuploids pregnancies is more common in
younger women.
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2. Emery's Elements of Medical Genetics 13 th
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Ellard.2009
3. Nussbaum et al Genetics in Medicine
(Edition 7.0), Saunders 2007
4. Rubin E., Farber J.L. [1999]. Pathology [3rd
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5. Noviski, Edwards (1977) Human Gentics-
p1:16-NY.
6. Strachan-Tomand read andrewp (1999)-
Human molecular Genetics second edition
p 47-49 bios scientific publisher, oxford, uk.
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Source of Support : Nil, Conflict of Interest : None declared

40 Central India Journal of Dental Sciences, Vol. 4 (1), Jan - Mar 2013

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