Chromosomal abnormalities
Mohammad Khassawneh
Assistant Professor of Pediatrics
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
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
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
When to suspect it
 Unexplained
infertility/ balanced
translocation
 Multiple abortion >2
 Prior case of defective baby
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%).
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
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)
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
Trisomy 18
 Incidence
1/8000
 Overlaps with trisomy 13
 Sever Mental retardation
 >90% dead in 1st year
Trisomy 18
 Small
face with prominant occiput
 Small sternum and pelvis
 Flexion deformity of the finger
 VSD and horseshoe kidney
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
Trisomy 13
 Sever
developmetal retardation
 Incidence 1/20000
 90% dead in the 1st year
Trisomy 13
 Midline
brain defect
 Malformed ear
 Microophalmos and coloboma
 Scalp defect
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
Continue turner syndrome
 Normal
IQ scale with difficulty in spatial
orientation such as map
 Present with short stature or delay sex
maturation
 Hormonal therapy
continue
 Mosaisim
(15%), remove gonads
 Recurrent risk is 1-2%
 Noonan syndrom AD, fresh mutation
 Pulmonary stenosis, nl stature,
microceph, mental retardation
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
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
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
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
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
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
Chromosomal linked disorder

Smith Lemli opitz syndrome

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CHARGE

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
Low cholesterol
High 7 dehydrocholesterol
Like trsomy 18
Coloboma
Heart
Atresia of choanae
Retarded
Genitalia hypoplasia
Ear anomalies
VATER