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

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.

11. Chromosomal disorders
Number
structure

12. Chromosomal disorders
Number
structure
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

16. Trisomies
Monosomies

17. Trisomies
Monosomies

18. Trisomies
3 copies of a particular chromosome

19. Trisomies
Trisomy 21
Klinefelter
Trisomy 18
Trisomy 13

20. Trisomies
Trisomy 21
Klinefelter
Trisomy 18
Trisomy 13

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.

27. Trisomies
Down syndrome
Klinefelter
Trisomy 18
Trisomy 13

28. Trisomies
Down syndrome
Klinefelter
Trisomy 18
Trisomy 13

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.

33. Trisomies
Down syndrome
Klinefelter
Edwards syndrome
Trisomy 13

34. Trisomies
Down syndrome
Klinefelter
Edwards syndrome
Trisomy 13

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

39. Trisomies
Down syndrome
Klinefelter
Edwards syndrome
Patau syndrome

40. Trisomies
Down syndrome
Klinefelter
Edwards syndrome
Patau syndrome

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

45. Trisomies
Monosomies

46. Trisomies
Monosomies

47. Monosomies
ONLY one copy of a particular chromosome

48. Monosomies
Turner syndrome

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

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

51. Turner syndrome Heart: MC: coarctation of aorta Kidneys:
Horse-shoe kidneys.
Stature: short
Hypothyroidism.

52. Turner syndrome Streak gonads. Amenorrhea.
Lack of 2ry sexual characteristics.

54. Chromosomal disorders
Number
structure

55. Chromosomal disorders
Number
structure

56. Deletion
Duplication

57. Loss of a portion of chromosome
Deletion
Duplication
Loss of a portion of chromosome

58. Deletion
Duplication

59. Syndromes involving chromosomal deletions
1. Cri du Chat syndrome
2. Williams syndrome
3. WAGR syndrome
4. Prader-Willi syndrome
5. Angelman syndrome

60. Syndromes involving chromosomal deletions
1. Cri du Chat syndrome
2. Williams syndrome
3. WAGR syndrome
4. Prader-Willi syndrome
5. Angelman syndrome

61. Cri du Chat syndrome Deletion of the short arm of ch.5
Most cases: de-novo.

62. Cri du Chat syndrome C|P: LBW Hypotonia FTT Develpmental delay
Microcephaly

63. Cri du Chat syndrome Dysmorphism: Congenital heart diseases.
Hypertelorism.
Epicanthal folds.
Downward obliquity of the papebral fissures.
Low-set malformed ears.
Cleft lip & palate.
Congenital heart diseases.

64. Syndromes involving chromosomal deletions
1. Cri du Chat syndrome
2. Williams syndrome
3. WAGR syndrome
4. Prader-Willi syndrome
5. Angelman syndrome

65. Williams syndrome
Deletion of ch. 7q11
Most cases: de-novo.

66. Williams syndrome C|P: Congenital heart diseases 80% Stature: short
Elfin facies
Moderate MR (IQ= 50-60)
Autism 10%
hypercalcemia
Coktail party personality

67. Syndromes involving chromosomal deletions
1. Cri du Chat syndrome
2. Williams syndrome
3. WAGR syndrome
4. Prader-Willi syndrome
5. Angelman syndrome

68. WAGR syndrome Deletion of 11p13 WAGR = Wilms tumor Aniridia
Genito-urinary anomalies:
Mental Retardation

69. Syndromes involving chromosomal deletions
1. Cri du Chat syndrome
2. Williams syndrome
3. WAGR syndrome
4. Prader-Willi syndrome
5. Angelman syndrome

70. Prader Willi & Angelman syndromes
Both are due to deletion of ch. 15q11
Both are caused by “genomic imprenting”.
NON-HERITABLE change in DNA.

71. Prader Willi & Angelman syndromes
If Paternal ch. 15 is missing, either due to:
1- Deletion of paternal ch. 15
2- Uni-parental disomy:
Duplication of maternal ch. 15 in absence of the paternal chromosome
The result is : Prader-Willi syndrome

72. Prader Willi & Angelman syndromes
If Maternal ch. 15 is missing, either due to:
1- Deletion of maternal ch. 15
2- Uni-parental disomy:
Duplication of paternal ch. 15 in absence of the maternal chromosome
The result is : Angelman syndrome

73. Prader-Willi syndrome
C|P: MR
Hypotonia:
Improved during the 1st year
Almond-shaped eyes
Small hands & feet
Hypogonadotropic hypogonadism
obesity

74. Angelman syndrome = Happy Puppet syndrome
C|P: MR
Ataxic movements:
Resembling a puppet gait
Seizures:
Characterized by inappropriate laughter

75. Deletion
Duplication

76. Duplicated part of a chromosome, within a chromosome
Deletion
Duplication
Duplicated part of a chromosome, within a chromosome

77. Deletion
Duplication

78. Syndromes involving chromosome duplication
1. Inverted duplication chromosome 15
2. Cat-Eye syndrome

79. Syndromes involving chromosome duplication
1. Inverted duplication chromosome 15
2. Cat-Eye syndrome

80. Inverted duplication chromosome 15
40% of syndromes involving chromosome duplication.
47,XX +inv dup (15q)
47,XY +inv dup (15q)
The larger the lesion, the worse the prognosis

81. Syndromes involving chromosome duplication
1. Inverted duplication chromosome 15
2. Cat-Eye syndrome

82. Cat-Eye syndrome Duplication of 22q11
Iris coloboma = cat-eye appearance

83. Cat-Eye syndrome C|P: Iris coloboma Mild MR Behavioral disturbances
Ocular hyper-telorism
Downward slanting palpebral fissures
Micrognathia
Anal atresia with recto-vestibular fistual & renal agenesis