Chromosomal Abnormalities with images

1. Chromosomal
Abnormalities &
clinical presentations
Dr.MD.Firoz
1st year post graduate
Andhra medicalcollege

2. Basics of chromosomes
 Term Chromosome derived from greek
words(chroma;colour)(soma;body) because of its
strong staining with dyes
 Chromosome is made up of DNA ,histone proteins
and chaperone proteins
 Human cell contain 23pairs of chromosomes ;22
pairs are autosomes and one pair is sex
chromosomes

4. Karyotype: it is a image or photograph of standard
arrangement of chromosomes in decreasing order of their
length

5. Cells used for chromosomal analysis
 Any cell with a nucleus can be used but actively dividing
cells are preferred
 Lymphocytes
 Skin cells
 Tumor cells
 Amniotic cells
 Chorionic cells
 Rare fetal cells from maternal blood

7.  Other cytogenetic studies used for chromosomal analysis
are
 FISH (fluorescent in situ hybridisation technique)
 FISH is a cytogenetic technique that uses fluorescent
probes to detect the presence of small, submicroscopic
chromosomal changes that are beyond the resolution of
karyotype analysis.

8.  Genetic disorders are classified into 5types
 1)chromosomal disorders
 2)single gene disorders[mendelian disorders]
 3)mitochondrial disorders
 4)multifactorial disorders
 5)somatic cell genetic disorders

9. Chromosomal abnormalities
NUMERICAL
 Aneuploidy is a disorder of
chromosomal number
 No of chroms in a cell is not
in multiple of 23
 Mc clinically significant type
of chromosome abnormality
 Mc cause is non disjunction
STRUCTURAL
 Deletions
 Duplications
 Translocations
 Inversions
 Insertions
 Ring chromosomes

10. Aneuploidy
Autosomal aneuploidy
 Mc aneuploidy in live born
children
 Downs syndrome(trisomy21)
 Edward
syndrome(trisomy18)
 Patau syndrome(trisomy13)
 Others are trisomy 16,9,8,
tetrasomy 12p
Sex chromosome aneuploidy
 Klienefelter syndrome
 Tuners syndrome
 Others are xyy male,
trisomy x,xy female

11. Downs syndrome(trisomy21)
 Down syndrome was the 1st chromosome aberration to be
discovered in humans by the physician John Langdon Down
in 1886.
 It affects about 1 in 800 live births
 Mc cause is non disjunction of maternal chromosome -
95%,translocation of the long arm of chromosome 21 to
usually chromosome14 or 15-4%(familial downs),mosaic
downs1%
 the risk of having a baby with Down syndrome increases
with maternal age

12. Screening tests:
 In 1st trimester: PAPP-A(pregnancy assc plasma protein),beta
HCG, Nuchal translucency
 In second trimester: QUAD TEST with AFP, estriol, HCG,
inhibin A (80%)
 Most affected individuals are mildly to moderately mentally
retarded, have congenital heart defects, and a high risk of
acute leukemia. They are usually short, have a broad, short
skull, and possess hyper flexible joints, intellectual disability,
females may reproduce but not males.
 Life expectancy is 17 years, however, 8% make it upto 4o
years.

13. Downs syndrome

14. Edwards syndrome(trisomy18)
 Edwards syndrome affects 1 in 10 thousand live births
 Most affected fetuses fail to survive to birth. Those that survive are
usually female, with 80–90% mortality by 2 years of age

15. Patau syndrome(trisomy13)
 Affects 1 in 20 thousand live births

16.  Other rare autosomal aneuploidies are
 Trisomy 8
Karyotype 47XX/XY,+8
characterised by growth deficiency , intellectual disability,
and deep palmar and plantar furrows
 Trisomy 9
karyotype 47XX/XY+9
characterised by craniofacial, skeletal malformations and
heart defects
 Trisomy 16
M/C observed autosomal aneuploidy in spontaneous abortions

17.  Tetrasomy 12p
Karyotype 46XX+[12]
Its known as pallister killian syndrome
characterised by sparse anterior scalp hair,
eyelashes, prominent forehead, polydactyly
and streaks of hyperpigmentation and
hypopigmentation patches

18. Klinefelter syndrome(47xxy)
 This is the mc sex chromosome
aneuploidy in humans
 It’s the mc cause of hypogonadism and
infertility in males
 prevalence is 1/580 males
 Error in paternal chromosome
disjunction is the mc cause
 Puberty occur at normal age but delay
in secondary sexual characters
 Main Clinical presentation will be
infertility

19. Turner Syndrome(45xo)
 Its monosomy of x chromosome
 Birth prevalence is 1/5000 female live births
 In 75% patients the lost chromosome is of paternal in origin
 Turners patients have assc cardiac defects in 40%.mc defect
is nonstenotic bicuspid aortic valve ,other are coarctation of
aorta,AS,MVP
 Renal malformations like horse shoe kidney,pelvic kidney
 Turners pt with mosaicism having y chromosome should
under go prophylactic gonadectomy because of high risk of
gonadoblastoma

20. Turners syndrome

21.  Other sex chromosome aneuploidies are
 47XYY syndrome
karyotype is 47XYY
they have normal intelligence with increased risk of
learning disabilities ,and hyperactive behaviour,
Earlier reports that assign stigmata of criminality to this
disorder has been disproved

22. Structural abnormalities
 The structure of chromosome is alter here
 Deletions: A portion of the chromosome is missing or
deleted.

23. example;
wolf hirshhorn syndrome
Its caused by partial deletion of p arm chromosome 4
c/f ;greek helmet facies ,hypertelorism,
Frontal bossing, microcephaly,
down turned corners of mouth
Beaked nose with prominent ridges

24.  Duplications: A portion of the chromosome is duplicated,
resulting in extra genetic material.

25. example;
 Charcot-Marie-Tooth disease
type 1A which may be caused by
duplication of the gene encoding
peripheral myelin protein 22 (PMP22)
on chromosome 17
 The neuropathy of CMT affects
both motor and sensory nerves.
Motor nerves cause muscles to contract

26.  Contiguous gene syndrome:
it is characterised by microdeletions
and microduplication involving many genes
so that the affected individual have a
distinct phenotype based on genes
involved
ex; Williams syndrome

27. Williams syndrome
Microdeletions in 7q11.23
 It has distinct ‘elfin facies’
stellate pattern in irish ,
intellectual disability,
supravalvular aortic stenosis
other cvs problems

28.  Translocations: A portion of one chromosome is
transferred to another chromosome.
 There are mainly of two types of translocations:
 • Reciprocal translocation
 • Robertsonian translocation

29.  • Reciprocal translocation :
Segments from two different chromosomes have been
exchanged.
Carriers are phenotypically normal but are increased risk of
miscarriages

30.  • Robertsonian translocation:
 Mc structural chromosome abnormality in humans
 With a Frequency of 1/1000
 These occur with acrocentric chromosomes 13, 14, 15, 21 and
22.
 They are named after the American biologist William Rees
Robertson who described it first in grasshopper
 The two chromosomes break at their centromeres and the long
arms fuse to form a single chromosome with a single centromere.
 Carriers of robertsonian translocations are phenotypically N but
increased risk of miscarriage and unbalanced abnormal offsprings

31. Inversions: A portion of the chromosome has broken off,
turned upside down and reattached, therefore the genetic
material is inverted and sequence is disturbed.
Carriers may phenotypically normal but increased risk of
miscarriages

32.  Insertions: A portion of one chromosome has been deleted
from its normal place and inserted into another chromosome.

33.  Rings: A portion of a chromosome has broken off and formed a
circle or ring. This can happen with or without loss of genetic
material
 Person with ring chromosome may appear normal or near normal
or can have intellectual disability

34.  Chromosome instability syndromes are a group of
disorders characterized by chromosomal instability and
breakage.
 They often have increased tendency to develop certain
types of malignancies

35.  Most chromosome abnormalities occur as an accident in
the egg or sperm, and therefore the anomaly is present in
every cell of the body.
 Some anomalies, however, can happen after conception,
resulting in Mosaicism (where some cells have the
anomaly and some do not).