Chromosomal Anomalies (Lecture 2)

1. 30.10.2014 Chromosomal Anomalies(Lecture 2) Dr. Archana Rani Associate Professor Department of Anatomy KGMU UP, Lucknow

2. Trisomy of Sex Chromosomes • Klinefelter syndrome • Triple X syndrome • Double Ysyndrome

3. Klinefelter Syndrome • Chromosome complement: 47,XXY • Phenotype: Male • Incidence: 1:1000

4. Features of Klinefelter Syndrome • Tall stature; thin build; long lower limbs • Testicular atrophy • Female pattern of pubic hair • High pitched voice • Infertility (aspermatogenesis) • Gynaecomastia • Low level of intelligence • Serum testosterone levels low to normal • FSH and LH levels very high • Sex chromatin positive

5. Klinefelter syndrome: Karyotype

6. Klinefelter Syndrome

7. Triple X Syndrome (Superfemale) • Chromosome complement: 47,XXX • Phenotype: Female • Incidence: 1:1000

8. Features of Triple X Syndrome • Normal in appearance • Difficulty in speech, learning and emotional responses • Mild mental retardation in 15-25% cases • Two sex chromatin Barr bodies • Infertility • Wide-set eyes • Amenorrhoea • Expressionless face • Enamel hypoplasia • Deficient language skills • Delayed development of motor skills

9. Superfemale: Karyotype

10. Superfemale

11. Double Y Syndrome • Chromosome complement: 47,XYY • Phenotype: Male • Incidence: 1:1000

12. Features of Double Y Syndrome • Normal in appearance • Tall stature • Aggressive behaviour • Problems in motor and language development

13. Monosomies of Chromosomes • Presence of only one member of a chromosome pair in a karyotype • More detrimental than equivalent trisomy • Can involve autosomes or sex chromosomes • Usually abort spontaneously • Monosomy of X chromosome results in XO condition called Turner syndrome

14. Turner Syndrome • Chromosome complement: 45,XO • Phenotype: Female • Incidence: 1:5000-8000

15. Features of Turner Syndrome • Short statured female • Sexual infantilism with primary amenorrhoea and sterility • Short, webbed neck • Prominent ears with defective hearing • Small mandible • Defective vision

16. Features of Turner Syndrome • Epicanthal folds • Low posterior hair line • Cubitus valgus • Broad chest with widely spaced nipples • Cardiovascular anomalies • Hyperconvex finger nails • Pigmented nevi • Sex chromatin negative

17. Turner Syndrome: Karyotype

18. Turner Syndrome

19. Structural Chromosomal Abnormalities • Results from chromosome breakage • Followed by reconstitution in an abnormal combination • Breaks in any chromosome may be induced by various factors

20. Structural Chromosomal Abnormalities • Deletion (Deficiency) • Inversion • Translocation • Isochromosome • Ring Chromosome

21. Deletion • Loss of a (generally small) segment of chromosome A B D E F G A B C D E F G C

22. Deletion • Arise through spontaneous breakage • some chromosomes have fragile spots • radiation, UV, chemicals, viruses may increase breakage

23. A B C D E F G x A B C D E F G A B C D E G A B C D E F F G Deletion Duplication Deletion • May arise through unequal crossing over

24. Deletions in Humans • Cri-du-chat syndrome • Micro deletion of chromosome 5 • Di-George syndrome • Micro deletion of chromosome 22 • Schizophrenia & Obsessive Compulsive Disorder • Micro deletion of chromosome 22 associated • Angelman syndrome • Micro deletion of chromosome 15 • Prader-Willi syndrome • Micro deletion of chromosome 15

25. Cri-du-chat syndrome • 1st autosomal deletion described • Characteristic cat-like cry, which disappears with age • Microcephaly • Severe mental retardation • Congenital heart disease • Hypertelorism (widely separated eyes) • Low birth weight and poor growth • Severe cognitive, speech, and motor delay • Behavioral problems • Excessive drooling

26. Cri-du-chat syndrome

27. Lack of muscle tone in newborn Poor swallowing reflex As adult - gross obesity Mean I.Q. ~ 50 Microdeletion of 15 Developmentally delayed Jerky movements Stiff, fixed smile Uncontrolled laughter Abnormal E.E.G., epilepsy Microdeletion of 15 Prader-Willi and Angelman Syndromes Prader-Willi Syndrome Angelman Syndrome

28. 180O A B C H G F E D I J K Inversion • 180o reversal of chromosome segment A B C D E F G H I J K

29. Inversion • Produced through breakage and reassociation of chromosome D E C B A F G

30. Inversion • Produced through breakage and reassociation of chromosome D E C B A F G

31. Types of Inversion Paracentric Pericentric

32. Translocation • Exchange of segments between non-homologous chromosomes F E L D M N O P C B Q A

33. Translocation A B C O N M L Q P D E F

34. Isochromosome • Centromere of the chromosome divides transversely instead of longitudinally • One arm is missing and the other arm duplicated

35. Ring Chromosome • Occurs due to loss of both the ends of a chromosome • The broken ends rejoin to form a ring-like chromosome • Rare anomaly

36. Robertsonian Changes • Fusion two chromosomes join to form one • Fission one chromosome splits to form two

37. REFERENCES 1. Essentials of Anatomy for Dentistry Students,1st Edition. 2. Langman’s Medical Embryology,11th Edition. 3. Human Embryology, 5th Edition.

38. MCQs 1. Klinefelter syndrome is associated with chromosome complement: a) 47,XXX b) 47,XXY c) 47,XYY d) 47,YYY

39. MCQs 2. Testicular atrophy is associated with: a) Triple X syndrome b) Double Y syndrome c) Turner syndrome d) Klinefelter syndrome

40. MCQs 3. Sex chromatin negative is a characteristic feature of: a) Triple X syndrome b) Down syndrome c) Turner syndrome d) Klinefelter syndrome

41. MCQs 4. All of the following are trisomy of sex chromosomes except: a) Turner syndrome b) Klinefelter syndrome c) Triple X syndrome d) Double Y syndrome

42. MCQs 5. Partial deletion of short arm of chromosome 5 is a feature of: a) Angelman syndrome b) Prader -Willi syndrome c) Cri-du-chat syndrome d) All of the above