Chromosomal Disorders

1. Chromosomal Disorders Fahd Alshehri Ali Almater Abdulrahman Alqahtani Abdullah Alshehri Abdullah Alshahrani

2. Case scenario • A 36-years old woman, G3P2 with one prenatal visit at 35 weeks but otherwise uneventful prenatal course delivers a 3900g female child. • At birth the infant is noted to have decreased tone, upslanting palpebral fissures and epicanthal folds. • The extremities show single transverse palmar crease

5. So, • Advanced maternal age • Hypotonia • Dysmorphic features: palpebral fissures epicanthal folds simian crease

6. What do you think? • Down Syndrome. • What is your next step? • Karyotype

8. What is the management? • Variable • How to prevent? • Genetic counselling.

9. Screening? • Should be offered ONLY when termination of pregnancy is acceptable.

10. What is “chromosomal disorders”? • Any disorder that results in an abnormal chromsomal sets.

12. EUPLOIDY 46, XY

13. Numerical chromosomal disorders • Euploidy: = 2n = 46 chromosomes • Aneuploidy: ≠ 2n is the state of not having euploidy Examples: Down syndrome Turner syndrome

14. Risk factors 1- advanced maternal age: Increases the incidence of meiotic errors (non-disjunction). 2- history of unexplained 1st TM abortions. 3- exposure to irradiations. 4- previous baby with chromosomal disorder.

15. Aetiology • Non-disjunction • Abnormal separation of chromosomes during cell division. • The result: • Extra chromosome = trisomy • Missing a chromosome = monosomy

18. Trisomies 3 copies of a particular chromosome

21. Trisomy 21 • Down syndrome • 47,XX+21 • 47,XY+21 • The MC abnormality of chromosomal number.

22. Trisomy 21 • 96% non-disjunction • 4% translocation of the long arm of chromosome 21 to chromosome 22

23. Trisomy 21 • C|P: • Hypotonia: improves with age • Characteristic facial features: • Flattened occiput • Upslanting palpebral fissures. • Epicanthal folds. • Large protruding tongue. • Short broad hands. • Transverse palmar crease. • Wide gap between the first and second toes.

25. Trisomy 21 • Intellectual disability • 40% congenital heart disease: • The cause of early-life deaths • 10% GI anomalies: • Duodenal atresia

26. Trisomy 21 • Increase risk of leukemia. • More susceptible to infection. • More risk of cataract. • Early-onset Alzheimer disease.

29. Trisomy 18 • Edwards syndrome. • 2nd MC. • 47,XX +18 • 47,XY +18 • ˃ 95% aborted. • ˂ 10% survive the 1st year.

30. Trisomy 18 • C|P: • LBW • MR • Hypertonia • Prominent occiput • Low-set malformed ears • Short stature • Clenched fists.

31. Trisomy 18 • Microcephaly, micrognathia. • Congenital heart disease. • Rocker-bottom feet, hammer toe. • Omphalocele.

35. Trisomy 13 • Patau syndrome. • 3rd MC. • 47,XX +13 • 47,XY +13 • ˂ 8% survive the 1st year.

36. Trisomy 13 • C|P: • LBW • Microcephaly • Midline facial defects • CNS anomalies & MR

37. Trisomy 13 • Male: Hypospadias & cryptorchidism • Female: Hypoplastic labia minora

41. Klinefelter syndrome • 47,XXY • MC cause of hypogonadism in males • Caused by non-disjunction

42. Klinefelter syndrome • C|P: • With puberty: • Presence of Pubic & axillar hair with testis of an infantile volume. • Tall & long limbs. • Slim. • Osteopenia, osteoporosis. • Gynecomastia

43. Klinefelter syndrome ↑ LH ↓testesterone So, affected individuals are infertile

47. Monosomies ONLY one copy of a particular chromosome

48. Monosomies Turner syndrome

49. Turner syndrome • The ONLYmonosomic viable condition. • 45, X0 • 99% aborted, constituting 13% of all 1st trimester abortions. • 25% mosaic. • Caused by mitoticnon-disjunction (post-conceptus mitotic non-disjunction event). • So, maternal age is not a risk factor.

50. Turner syndrome • C|P: • Facial characteristics: • Low-set malformed ears. • Triangular face. • Flattened nasal bridge. • Epicanthal folds. • Neck: webbed. • Chest: • Shield-shaped. • Widened inter-nipple distance.