Chromosome abnormalities Ajith Sominanda Department of Anatomy Faculty of Medicine Peradeniya

Development of cytogenetic techniques to analyze chromosomes led to discovery and characterization of chromosome disorders (1950s) Within years (from 1956), the cause of Down syndrome (47,XX/XY+21) Turner syndrome (45,X) and Klinefelter sysndrome (47,XXY) was established Now more than 20,000 chromosome abnormalities have been reported but these conditions are very rare in the population Chromosome abnormalities are a major cause for early pregnancy loses

Types of chromosome abnormalities Numerical abnormalities (Abnormal changes in the chromosome number in a cell) Structural abnormalities (abnormalities of the chromosome structure Others

Failure of chromosomes to seggregate (move) during cell division : Non-dysjunction Normal Gametes Mono somic gametes Nullisomic gametes

Non dysjunction Occurs with advancing age; especially maternal age Maternal oocytes have a long delay between different phase of the cell division With advancing age, spindle formation become defective and leads to non dysjunction

Gametogenesis in female and risk of non dysjunction

Gametogenesis in male

Numerical abnormalities Aneuploidy (loss or gain of one or more chromosomes) Monosomies (loss of a single chromosome) 45,X - Turner syndrome (loss of one sex chromosome) Monosomy of autosomes are incompatible with life Trisomies (Presence of an extra chromosome) Trisomy 21 (Down’s syndrome) Trisomi 18 (Edward’s syndrome) Trisomi 13 (Patau Syndrome) XXY (Klinefelter syndrome) XXX (XXX females) XYY (XYY males) Tetrasomies (Presence of two extra chromosome)

(Addition of one or more haploid set of chromosomes) Polyploidy (Addition of one or more haploid set of chromosomes) Triploidy (3n 46+23=69) Tetraploidy (4n 46+46=92) Retension of polar bodies or fertilization with 2 or 3 sperms can lead to polyploidy Tetraploidy (23+23+23+23=92) Triploidy (46+23=69) Triploidy (23+23+23=69) 23 23 23 23 23 23 46 23 23 Ovum polar body

Monosomies (loss of a single chromosome) Turner syndrome Karyotype is 45,X

Trisomies (Presence of an extra chromosome) Down Syndrome Trisomy 21 (47,XX/XY+21)

Trisomies (Presence of an extra chromosome) Edward syndrome Trisomi 18 (47, XX/XY, +18)

Trisomies (Presence of an extra chromosome) Patau syndrome Trisomi 13 (47, XX/XY, +13)

Trisomies (Presence of an extra sex chromosome) Klinefelter syndrome (47, XXY) Slightly femine figure Has low IQ and Learning difficulty Infertile

Trisomies (Presence of an extra sex chromosome) XXX females (47,XXX) Looks normal in phenotype Slightly less IQ Fertile

Trisomies (Presence of an extra sex chromosome) XYY males Tall Aggressive Low IQ and learning difficulties Normal fertility

Structural abnormalities Translocations Deletions Insertions Inversions Rings chromosmoes Isochromosomes

Types of translocations

Insertion

Inversion

Mosaicism is caused by an error in cell division very early in the development of the unborn baby due to chromosome abnormality

Chimerism chimera or chimaera is a single organism composed of two or more genetically distinct cellspopulations from different zygotes