2. Chromosomal abnormalities Types of Chromosomal abnormalities  Numerical abnormalities Aneuploidy: trisomy (2n+1), monosomy (2n-1), tetrasomy (polysomy) (2n+2) Result from Non-disjunction at meiosis or mitosis Polyploidy: triploidy (3n), teteraploidy (4n),and so on Result from Karyokinesis without cytokinesis  Structural abnormalities

3. Numerical abnormalities  Polyploidy Metaphase chromosomes of triploidy Spontaneous abortion (1%) Embryonic mortality (99%)

4. Numerical abnormalities-cont’d  Aneuploidy

5. Clinical features 1-Flat broad face 2- Single palmar crease (Simian crease) 3-Squint 4-Mental retardation Aneuploidy of autosomes : Trisomy 1-Trisomy 21(47,XX,+21 or 47,XY,+21) (Down ׳s syndrome) Results from:  Pure trisomy 95%  Translocation 3%  Mosaicism 2%

6. Aneuploidy of autosomes : Trisomy-cont’d G-banding karyotype of 47,XX,+21 Trisomy 21(Down ׳s syndrome) 1-Trisomy 21(47,XX,+21 or (47,XY,+21) (Down ׳s syndrome)

7. Clinical features 1- Fixed flexion fingers with characteristic grasp (overlapping the 2nd and 5th fingers over 4th finger) 2-Small jaw 3- Elongated occiput 4- Incompatible with life Aneuploidy of autosomes : Trisomy-cont’d 2-Trisomy 18 (47,XX,+18 or 47,XY,+18) (Edward׳s syndrome) Results from:  Pure trisomy (Most of cases)  Mosaicism and Translocation also observed

8. G-banding karyotype of 47,XY,+18 Trisomy 18 (Edward׳s Syndrome) Aneuploidy of autosomes : Trisomy-cont’d 2-Trisomy 18 (47,XX,+18 or 47,XY,+18) (Edward׳s syndrome)

9. Clinical features 1- Cleft lip and palate 2- Polydactyly (extra finger) 3- Incompatible with life Aneuploidy of autosomes : Trisomy-cont’d 2-Trisomy 13 (47,XX,+13 or 47,XY,+13) (Patau׳s syndrome) Results from:  Pure trisomy (Most of cases)  Mosaicism and Robertsonian translocation also observed.

10. G-banding karyotype of 47,XY,+13 Trisomy 13 (Patau׳s syndrome) Aneuploidy of autosomes : Trisomy-cont’d 2-Trisomy 13 (47,XX,+13 or 47,XY,+13) (Patau׳s syndrome)

11. Clinical features 1-Long Stature 2-Breast development 3-Small testis 4- Azoospermia Aneuploidy of sex chromosomes : Trisomy Klinefelter׳s syndrome Results from:  Extra one X chromosome

12. Aneuploidy of sex chromosomes : Trisomy-cont’d Klinefelter׳s syndrome G-banding karyotype of 47,XXY Aneuploidy of sex chromosomes (Klinefelter׳s syndrome)

13. Clinical features 1-Short stature 2- Webbed neck 3- streak gonads 4- compatible with life Aneuploidy of sex chromosomes : Monosomy Turner׳s syndrome Results from:  Missing one X chromosome (most cases)  Mosaicism  Isochromosome  Ring chromosome  Deletion

14. Aneuploidy of sex chromosomes : Monosomy-cont’d G-banding karyotype of 45,X0 Monosomy X (Turner׳s syndrome) Turner׳s syndrome

15. Mosaicism  Down ׳s syndrome (46,XY/ 47,XY,+21)  Edward׳s syndrome (46,XX/ 47,XX,+18)  Patua׳s syndrome (46,XY/ 47,XY,+13)  Turner׳s syndrome (46,XX/ 45,X0) Result from Non-disjunction at zygotic mitotic division

16. Structural abnormalities  Deletion  Inversion  Ring chromosome  Isochromosome  Translocation  Insertion  Duplication

17. Clinical features 1-Underdevelopment of larynx hence affected new born make characteristic cat like cry 2-Microcephaly Structural abnormalities-cont’d Deletion-Terminal deletion Cri-due chat syndrome Results from:  Terminal deletion

18. G-banding karyotype of 46,XX,5p- Cri-due chat syndrome Structural abnormalities-cont’d Deletion-Terminal deletion Cri-due chat syndrome

19. Giemsa stain karyotype of 46,XY,5p- Cri-due chat syndrome Structural abnormalities-cont’d Deletion-Terminal deletion Cri-due chat syndrome

20. Structural abnormalities-cont’d Translocation Types of Translocation:  Reciprocal translocation  Robertsonian translocation

21.  Reciprocal translocation Structural abnormalities-cont’d G-banding karyotype of 46, XX, t (3q;17q)

22.  Robertsonian translocation (centric fusion): Normal carrier Structural abnormalities-cont’d G-banding karyotype of 45,XX,-14,-21,+t(14q21q) Normal carrier

23. G-banding karyotype of 45,XY,-21,-21,+rob(21q21q) Structural abnormalities-cont’d  Robertsonian translocation (centric fusion): Normal carrier

24. How can normal carrier produce Down syndrome? Structural abnormalities-cont’d  Robertsonian translocation (centric fusion)-cont’d

25. Structural abnormalities-cont’d G-banding karyotype of 46,XY,-14,+rob(14q21q) (Down Syndrome)  Robertsonian translocation (centric fusion)-cont’d How can normal carrier produce Down syndrome?

26.  Isochromosome: Structural abnormalities-cont’d G-banding karyotype of 46, X, i (Xq) Turner syndrome