1. Chromosomal abnormalities
Mohammad Khassawneh
Assistant Professor of Pediatrics

2. introduction Normal human cells contain 23 pairs of chromosomes
This includes one pair of sex chromosome XX or XY
During cell division we can identify chromosomes
Lymphocytes incubated for 2-3 days or uncultured bone marrow in 4-24 hours

4. continue Haploid: set of 23 chromosomes
Diploid: normal number of 46 chromosomes
Aneuploidy: less than an even multiple of 23 usually is 45 or 47 and rarely 48,49
Triploidy: 69 chromosomes
Mosaicism
Abnormal in deletion and translocation(balanced and unbalanced)Balanced

5. Incidence The earlier the abortion the more likely to be chromosomal
50% of spontanous abortion are chromosomal abnormal
Mostly triploidy. 45 XO, trisomy 16
98% of fetus with turner abort
Generally 6/1000 the incidence of chromosomal abnormalities

6. When to suspect it Unexplained infertility/ balanced translocation
Multiple abortion >2
Prior case of defective baby

7. When to suspect it…continue
Presence of congenital anomalies
45% have minor single anomalies
9% 3 minor anomalies
1.5% HAVE major anomaly
2 or more major anomalies may represent genetic syndrome or chromosomal abnormalities(10%).

8. Down Syndrome Incidence 1/700 2/3 of down fetus spontaneously abort
Clinical diagnosis depend on gestalt
Trisomy 21 in 94% of cases with extra chromosome from mother mostly(95%)
Risk correlate with maternal age
<25 y/o 1/1600
>40 y/0 1/80
2% are mosaic

13. Other Clinical features
Hypotonia without weakness
Clinodactaly protruded tongue,small ears,brachycephaly,small up turned nose, depressed nasal bridge.
Mental retardation, socially do better with good environment (Happy children)

14. Clinical issues Cardiac and GI Hypothyriodism
Transient leukemoid reaction
Alzheimer’s disease up to 25% over 40 y/o
Early death relate to cardiac dysfunction

15. Trisomy 18 Incidence 1/8000 Overlaps with trisomy 13
Sever Mental retardation
>90% dead in 1st year

16. Trisomy 18 Small face with prominant occiput Small sternum and pelvis
Flexion deformity of the finger
VSD and horseshoe kidney

23. triploidy Complete extra set of chromosomes Mostly miscarriages
Fetal wastage skeleton more than cephalic, 2% survive to be recognized
Large hydatidiform placenta
VSD, ASD, Syndactaly
Genital and CNS abnormalities

25. Trisomy 13 Sever developmetal retardation Incidence 1/20000
90% dead in the 1st year

26. Trisomy 13 Midline brain defect Malformed ear
Microophalmos and coloboma
Scalp defect

32. Turner syndrome Most common abnormality in early abortion
Female, short stature, primary amenorrhea, sterility, spares hair and underdeveloped breast
Neonatal: wide spaced nipple, lymphedema , shield chest,
Coarctation of the aorta

33. Continue turner syndrome
Normal IQ scale with difficulty in spatial orientation such as map
Present with short stature or delay sex maturation
Hormonal therapy

34. continue Mosaisim (15%), remove gonads Recurrent risk is 1-2%
Noonan syndrom AD, fresh mutation
Pulmonary stenosis, nl stature, microceph, mental retardation

36. Klinefelter syndrome
20% of aspermic adult male (blocked spermatogenesis
47 XXY in 80% and mosaic in 20%
IQ is 98 (normal) with mild decrease in verbal IQ
Scoliosis, decrease libido may improve with testesterone, gynecomastia

38. Fragile X Syndrome Moderate to sever mental retardation
Speech delay, short attention, hyperactivity
Poor motor coordination and mouthing objects
Poor socialization, temper tantrum
Mood disorder (bipolar), schizophrenia

39. Fragile X syndrome Long protruding ears Long face and prominent jaw
Flattened nasal bridge
High arch palate
Macroorchidism
Genetic is complex, 80% penetration in male and 30% penetration in female

41. Genetic imprinting
Means: as genomes pass through miosis it is normal for part of it to change.
During miosis inactive X chromosome become active and changes on fragiloe X gene (imprinting) make it malignant

43. Angelman syndrome Sever mental retardation Inappropriate laughter
Decrease pigmentation of choroid or iris (pale blue eyes)
Ataxia and jerky eye movement
Sever speech proplem
Deletion of b15q11q13, maternal in origin
Paternal uniparental disomy

45. Prader-willi syndrome
(A fat red faced boy in state of somnolency) Charles Diickens
Early hypotonia
Obesity
Short stature as adult
Almond shaped blue eyes
Mental retardation (mild to moderate)
Narrow hands

46. Chromosomal linked disorder
Smith Lemli opitz syndrome
Low cholesterol
High 7 dehydrocholesterol
Like trsomy 18
CHARGE
Coloboma
Heart
Atresia of choanae
Retarded
Genitalia hypoplasia
Ear anomalies
VATER