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)
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.
8.
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.
11.
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
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.
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.
