2. Chromosomal aberrations
Definition :-
―Any deviation either in number or structure of the
chromosomes is referred as chromosomal aberrations‖
Types :-
1) Structural aberrations.
2) Numerical aberrations.

3. Terminologies:
 Diploid
 Hapliod
 Polyploidy : in multiple of ‗n‘
 Aneuploidy : any number which is not exactly a multiple
of ‗n‘
2n - 1 ------ > Turners syndrome (45X)
Or 2n + 1 ------ > Down‘s syndrome (47, trisomy 21)

4. Genesis of anuploidy
Non-disjunction in meiosis. Or after formation of zygote.

5. Structural aberrations
 Stable:–
- Deletions
- Translocation
- Insertion
- Inversions
- Isochromosomes
 Unstable:-
- Dicentric
- Ring chromosomes
May occur due to
a) Ionizing radiations
b) Chemical agents
c) viruses

6. Deletion
This Involves loss of a part of chromosome.
1. Terminal deletion.
2. Interstitial deletion.
1. Terminal deletion.
It involves a single break and the terminal part of the
chromosome is lost.
e.g. cri-du-chat syndrome

7. - Deletion of 5p arm
- Cry of baby
- Typical facial appearance
- Microcephaly, hypertelorism,
- Antimongoloid slant of
palpebral fissure.
- Low set ears, microganthia.

9. 2) Interstitial deletion.
It involves two breaks and the intervening portion of
the chromosome is lost.
 Wilm‘s tumor with anirida. (11q13)
 Prader- will syndrome. (15q11-13)
 Angelman syndrome. (15q11-13)
Microdeletion syndrome - Deletion of 3 – 4 Mb

10. Prader- will syndrome. (15q11-13)
- Inherited from father
- Short stature, hypotonia
- Obesity
- Small hands & feet
- Mild to moderate mental retardation
- Hypogonadism
Angelman syndrome. (15q11-13)
- Inherited from mother
- Severe mental retardation
- Seizures & ataxic gait
Difference is due to genomic imprinting.

12. Translocation
1) Robertsonian translocation
- Involves two acrocentric
chromosomes
- D/G Translocation
- Also called centric fusion
- In 4% of down‘s cases
- [50% from parents(balanced),
50% de novo in baby]

13. 2) Reciprocal Translocation
- Exchange of material distal to
breaks
- In non homologus chromosomes
- No chromosome material is lost
- Abnormal production of gamets
- Spontaneous abortions/ baby with
congenital malformations
- Carrier couple- repeated abortions.

14. Insertion
- Rare non-reciprocal type of translocation
- Involves 3 breaks
- 2 breaks to release fragment
- 1 break to admit fragment.

15. Inversions
 Pericentric – involves
both arms p & q
 Paracentric – either p or q
 Do not give abnormal
phenotype
 Abnormal gamets may
give abnormal progeny.

16. Isochromosomes
- Abnormal split along
the centromere
- Seperation of arms
- E.g. isochromosome X
(Xq)
- In some cases of
Turners syndrome

17. Ring chromosomes
- Two breaks at terminal ends
- Fusion of the cut ends
- 1/5th cases of turners syndrome

18. Factors playing role in chromosomal
aberrations
 Maternal age > 35 yrs
non-disjunction during meiosis 1
 Radiation
correlation between radiation and non-disjunction
 Chromosomal abnormalities
balnced translocation in parents may produce
aberrations in offsprings
 Autoimmune disorders - not clear
High titer of thyroid autoantibodies in mother
associated with Down‘s syndrome in their childrens

19. Numerical aberrations
 Autosomal :-
Trisomy 21 / Down‘s syndrome
Trisomy 18 / Edwards syndrome
Trisomy 13 / Patau syndrome
 Sex chromosome related :-
Turners syndrome / 45X
Polysomy X syndrome / e.g. XXX, XXXX
Klinfelters syndrome / 47 XXY

20. Autosomal
 Monosomies are fetal – Abortion.
 Trisomies are common.

21. Down’s syndrome / Trisomy 21
 1866 – first identified by Langdon
Down.
 1959- Lejeune & associates
demonstrated extra chromosome
no.21
 Mongolism
 Incidence- Approximately one in
1000 live births.

22. Clinical features
 Mental retardation –
predominant feature
 IQ – 25-50
 Small stature
 Hypotonia of muscles
 Brachycephaly with flat
occiput
 Epicanthal fold—mongoloid
slant
 Flat nose, low nasal bridge

23.  Mouth is open with
protruded tongue
 Highly arched palate
with delayed dentition
 Hands are short and
broad
 Cardiovascular defect in
1/10th cases.

24.  Ears are low set and malformed

25. Dermatoglyphics
 Simian crease- classical feature
 Wide gap between first and second toe.

26. Cytogenetics
 Trisomy 21 (47, +21), - 94 %, The frequency of trisomy
increases with increasing maternal age.
 Robertsonian translocation involving chromosome 21-
Approx. 3-4 %, not related to maternal age.
 Trisomy 21 mosaicism – 2 to 3 % cases

27. Karyotype of Down’s syndrome

28. Risk of Down’s syndrome
 Maternal age
 Does the couple already have baby with down’s
syndrome?
 What is karyotype of baby?(typical / translocation)
 Parent carrier of translocation?

29. Diagnosis
 Prenatal screening
 If no screening – It is recognized from the
characteristic phenotypic features.
 Confirmed by Karyotype.( chorionic villous biopsy ,
amniocentesis)

30. Management
Counseling
 May begin when a prenatal diagnosis is made.
 Discuss the wide range of variability in manifestation and
prognosis.
 Medical and educational treatments and interventions
should be discussed.
 Initial referrals for early intervention, informative
publications, parent groups, and advocacy groups.

31. Management cont..
1. Growth – Measurements should be plotted on the
appropriate growth chart for children with DS.
 This will help in prevention of obesity and early diagnosis
of celiac disease and hypothyroidism.
2. Cardiac disease – All newborns should be evaluated by
cardiac ECHO for CHD in consultation with pediatric
cardiologist.
3. Hearing – Screening to be done in the newborn period,
every 6 months until 3 yrs of age and then annually.

32. 4. Eye disorders - An eye exam should be performed in the
newborn period or at least before 6 months of age to detect
strabismus, nystagmus, and cataracts.
5. Thyroid Function – Should be done in newborn period and
should be repeated at six and 12 months , and then
annually.
6. Celiac Disease – Screening should begin at 2 yrs. Repeat
screening if signs/Sx develop.

33. 7. Hematology – CBC with differential at birth to evaluate for
polycythemia as well as WBC.
8. Atlanto-axial instability – X ray for evidence of AAI or sub-
luxation at 3 to 5 years of age.
9. Alzheimer‘s disease – Adult with a Down Syndrome has
earlier onset of symptoms. When diagnosis is
considered, thyroid disease and possible depression
should be excluded.