1. Chromosome disorders (2) Weiying Jiang Department of Medical Department P261

2. At least 20,000 Chromosome abnormality Numerical abnormality Structural abnormality Aneuploidy Polyploidy translocation deletion insertion inversion rings isochromosome

3. Diploidy 46 chromosomes

4. Numerical abnormality Aneuploid: One or a few chromosomes above or below the normal chromosome number. Polyploidy: More than two sets of chromosomes per nucleus. 23 chromosomes = one set of chromosomes

6. chromosome abnormality in spontaneous abortions 10 Other 5 Tetrepolidy 15 Triploidy 20 Monosomy X 25 Trisommy other 5 Trisommy 21 3 Trisommy 18 15 Trisommy 16 2 Trisommy 13 Incidence (%) Abnormality

7. Down’ syndrome Down syndrome is characterized by well-defined and distinctive phenotypic features and natural history. It is caused by trisomy of all or a critical portion of chromosome 21.

8. Down’ syndrome Incidence: 1/1000 in UK 60% cases found prenatally 1/800 in USA More than 350,000 people affected

9. Down’ syndrome Down’ syndrome

10. Clinic features of Down’ syndrome New born period Hypotonia Sleepy Excess nuchal skin

12. Clinic features of Down’ syndrome Mental retardation ： Average IQ 40-45 Social skill are relatively well advanced Average life span 50-60 years Most affected adults develop Alzheimer disease

13. Clinic features of Down’ syndrome Congenital malformations ( 40-45%) atrioventricular canal defect Heart ventricular septal defect Patent ducts arteriosus

14. Clinic features of Down’ syndrome Gastrointestinal tract

15. Ninety percent of all Down syndrome patients have a significant hearing loss, usually of the conductive type Clinic features of Down’ syndrome

16. Estimates of the relative risk of Leukemia have ranged from 10 to 20 times higher than the normal population; In particular, acute megakaryocytic leukemia occurs 200 to 400 times more frequently in the Down syndrome than in the chromosomally normal population. Clinic features of Down’ syndrome

17. Characteristic facies

18. 50% single palm crease

19. Gene map locus 21q22.3

20. Trisomy 21 (95%) : Patients have 3 free copies of chromosome 21. Chr. Abnormality in Down’ syndrome Translocation ( about 5% ): Patients have 1 copy to be translocated to another acrocentric chromosome, most often chromosome 14 or 21 mosaicism (2 to 4% ): Patients have a trisomic and a normal cell line

21. Trisomy 21 (95%)

22. Trisomy 21 Karyotype 47,XY, +21 47,XX, +21

23. Mechanism of Trisomy 21 Meiotic Non-disjunction

24. Normal XX X X l l l l

25. Translocation Down’s Syndrome Karyotype 14/21 translocation 46,XX(XY)., -14, +t (14q21q) 21/21 translocation 46,XX(XY)., -21, +t (21q21q)

26. Mechanism of Translocation Down’s Syndrome

27. 14 21 14 14/21 21 Carrier Normal 14 21 14/21 14 14 21 14/21 14/21 21 Down’s syndrome Lethal

28. Mosaicism (2 to 4% ): Mitotic Non-disjunction

29. Patau syndrome (Trisomy 13) 47,XX(XY),+13 Patau syndrome is a chromosomal condition that is associated with severe mental retardation and certain physical abnormalities. Small eyes An opening in the roof of the mouth (a cleft palate) and/or a cleft lip

30. An infant with trisomy 18 (Edwards syndrome), exhibiting characteristic facial features, short sternum, overlapping fingers with clenched fists, and a left-sided clubfoot . Edwards syndrome (Trisomy 18) 47,XX(XY),+18

31. Short stature Turner syndrome (45,X) Neck webbing Intelligence is normal, but learning is difficult.

32. Neck webbing

33. Turner syndrome (45,X) Ovarian failure Amenorrhea Infertility

34. Turner yndrome (45,X) During the second trimester, edema was detected by ultrasonography Thickened nuchal pad

35. Klinefelter syndrome (47,XXY) Klinefelter's syndrome is a condition that occurs in men who have an extra X chromosome in most of their cells . less facial and body hair IQ: reduced to 10-20 point infertility testosterone

36. Klinefelter syndrome (47,XXY)

38. Fragile X syndrome High forehead Large ears Long face Large testes Prominent jaw Learning difficulties are moderate to severe

39. FMR-Ⅰ5 ’ CGG Normal 10-50 CGG Intermediate 51-58 Premutation 58-200 CGG Full mutation >230 CGG Fragile X syndrome

40. Thank you !