2.

Structural aberration

Aberrations in chromosome structure result from the

breakage and reunion of chromosome segments
and may involve one, two, or more chromosomes.

When a chromosome breaks, two unstable sticky

ends are produced. Generally, repair mechanisms
rejoin these two ends without delay. However, if
more than one break has occurred, repair
mechanisms may not be able to distinguish one
sticky end from another and may rejoin the wrong
ends.
 Chromosome breaks can occur from:
1) spontaneous errors in replication or
crossing-over
2) mutations in genes that normally repair
breaks
3) environmental agents, such as ultraviolet
light, radiation(exposure to ionizing
radiation ), viruses, or chemicals.
chromosome structure changes

1) Deletion
2) Duplication and Insertion
3) Inversion
4) Translocation
 Deletiontion

Terminal
deletion Terminal
Interstitial
(short deletion
deletion
arm) (long arm)
Duplication—extra copies of a
chromosome segment
Inversio
— a reversal in the order of a
n
chromosome segment

An inversions occurs
when a single
chromosome undergoes
two breaks and is
reconstituted with the
segment between the
breaks inverted.
 pericentric paracentric
inversion inversion

Including the centromere, in Not including the

which there is a break in centeomere, in which both
each arm. breaks occur in one arm
 insertion,ins

An insertion is a
nonreciprocal type of
translocation that occurs
when a segment
removed from one
chromosome is inserted
into a different
chromosome, either in
its usual orientation or
inverted.
 Translocation—movement of a
segment of one chromosome to
another chromosome

Reciprocal translocations: This

type of rearrangement results from
breakage of nonhomologous
chromosomes,with reciprocal
exchange of the broken-off
segments. Usually only two
chromosomes are involved , and
because the exchange is reciprocal,
the total chromosome number is
unchanged.
(Robertsonian translocation, rob)
(balanced translocation)

This type of rearrangement involves

two acrocentric chromosomes that
fuse near the centromere region with
loss of the short arms.
ring chromosome,r

isochromosome,(i)
is a chromosome in which one
arm is missing and the other
duplicated in a mirror-image
fashion.
(unbalanced translocation)
chromosomal disorder
 summarization
Approximately 20% of all conceptions
have a chromosomal disorder, but most of
these fail to implant or are spontaneously
aborted so the birth frequency is 0.6%.

The frequency of chromosomal disorders

in early spontaneous abortions is 60%,
whereas in late spontaneous abortions
and stillbirths, the frequency is 5%.
Various surveys indicate that 1 in 119-154
livebirths have a major chromosomal
abnormality. Sex chromosome abnormalities
occur once in every 300-400 births.

In mothers over 35 ,this frequency is even

greater, about 1 in 250.
Commonest chromosomal disorders seen in
newborns
Disorder Birth frequency
Balanced translocation 1 in 500
Unbalanced translocation 1 in 2000
Pericentric inversion 1 in 100
Trisomy 21 1 in 700
Trisomy 18 1 in 3000
Trisomy 13 1 in 5000
47,XXY 1 in 1000 males
47,XYY 1 in 1000 males
47,XXX 1 in 1000 females
45,X 1 in 5000 females

Notice!
 Notice!
Not all of these chromosomal changes are
associated with disease, but generally
autosomal abnormalities tend to be more
severe than sex chromosomal abnormalities
and deletions more severe than
duplications.
 Common problem
1) Congenital abnormalities
2) Ambiguous genitalia
3) Delayed development , Short stature
4) Mental retardation
5) Two or more unexplained miscarriages
6) Infertility
7) Amenorrhoea
8) Abnormal or inappropriate physical sexual
development
9) Family studies known to carry cytogenetic
anomalies
10) Family history of Down syndrome
 Down syndrome
Down syndrome is the most common type of
trisomy that babies may be born with.   

The karyotype is written 47, XX ,+ 21 or 47,

XY ,+ 21. 
 Clinical Manifestations
1) Short stature
2) Special facial features
upslanting palpebral fissures,
epicanthus, brushfield spots on the
iris, protruding tongue, small ears
3) Mild to severe mental retardation
4) 80% of trisomy 21 conceptions
result in early miscarriage.  
5) heart problems
 karyotype
47,XX,+21
An extra chromosome
21 is the classic
chromosomal
constitution of
individuals with Down
Syndrome.

Partial trisomies of
chromosome 21 and
mosaicism has also
been observed
associated with Down
Syndrome.
 trisomy 21 Mosaic
XX
llll ll
X
ll
X
ll ll ll

X X X X
ll ll lll l
ll l l

Yl

46,XX(XY)/ 47,
XX(XY),+21
47,XX(XY),
+21
 trisomy 13 and trisomy 18

Trisomy 13, or Patau syndrome, and trisomy

18, Edward syndrome, are very severe
chromosome changes and both usually lead to
early infant death, often within the first year
of life.  Most trisomy 13 and 18 conceptions
result in early miscarriage.

An extra copy of any of the other autosomes

results in early miscarriage.
5P15.2
Changes in the number of sex chromosomes
Changes in the number of sex chromosomes has a
less severe effect on development and sometimes
individuals with extra sex chromosomes can even be
asymptomatic.

Examples of the inheritance of an extra sex

chromosome include: XXY, XXX or XYY.

Sex-chromosome abnormalities may also be caused

by nondisjunction of one or more sex chromosomes.
karyotype
 Turner syndrome

gonadal differentiation, no pubes,

undevelopmental breast, amenorrhea
infertile
short in stature, characteristic webbing of the
neck, low posterior hair line, cubitus valgus,
cardiac defects,
normal intelligence. (The majority of those that
do survive are probably ‘mosaics’ i.e. they have
a normal cell line in some tissues.)
Diagnosis
 Klinefelter Syndrome
47, XXY
men , enlarged breasts, sparse facial and body hair,
small testes, and an inability to produce sperm.
Overweight or taller.
Although they are not mentally retarded, most XXY
males have some degree of language impairment.
Femals body shap with gynaecomastia in aolescence,
breast cancer, hypogonadism
Many naevi
 Causes
No one knows what puts a couple at risk for
conceiving an XXY child.
Advanced maternal age increases the risk for the
XXY chromosome count, but only slightly.
recent studies show that half the time, the extra
chromosome comes from the father.
an egg with two Xs, or a sperm having both an X
and a Y chromosome..
Diagnosis
Treatment

Surgery, can reduce breast size.

Regular injections of the male hormone testosterone
Special education for compensating for language
disability.
 Testosterone
Treatment
Ideally, XXY males should begin testosterone
treatment as they enter puberty. XXY males
diagnosed in adulthood are also likely to benefit
from the hormone. A regular schedule of
testosterone injections will increase strength and
muscle size, and promote the growth of facial and
body hair.

In addition to these physical changes, testosterone

injections often bring on psychological changes as
well. As they begin to develop a more masculine
appearance, the self-confidence of XXY males tends
to increase. Many become more energetic and stop
having sudden, angry changes in moods.
 47,XYY
The abnormality has
a variable phenotype
that can include tall
stature and acne.
 49,XXXXY
This karyotype shows a variant of Klinefelter's syndrome.
Individuals with this syndrome are male, typically with the
karyotype 47,XXY.
They exhibit a characteristic
phenotype including tall stature,
infertility, gynecomastia and
hypogonadism.

Aneuploidy above one extra

chromosome is usually fatal but
because of X-inactivation, which
"turns off" all but one X
chromosome per cell, the
effects of 3 extra chromosomes
are reduced.
 Gonadal Dysgenesis
A syndrome of gonadal dysgenesis in which there
is a testis on one side and a "streak gonad" on the
other. The phenotype is generally male, but may
be female since the individual is a mosaic.

Various karyotypes have been identified,

including 45,XO/47,XYY; 45,XO/46,XY; and
45,XO/46,XYo.
 Prenatal detection ---
amniocentesis
Prenatal detection of chromosomal abnormalities
is accomplished chiefly by amniocentesis. A thin
needle is inserted into the amniotic fluid
surrounding the fetus (a term applied to an unborn
baby after the first trimester). Cells are withdrawn
have been sloughed off by the fetus, yet they are
still fetal cells and can be used to determine the
state of the fetal chromosomes such as Down's
Syndrome and the sex of the baby after a
karyotype has been made.