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Abnormalitas Kromosom

 Chromosomes are tiny,
string-like structures in
cells of the body that
contain the genes.

 Each person normally

has 23 pairs of
or 46 in all.
Chromosomal abnormalities
 Generally 5-6/1000 the incidence of
chromosomal abnormalities.
 These abnormalities are caused by errors in
the number or structure of chromosomes.
 Many children with a chromosomal
abnormality have mental and/or physical
birth defects.
 Some chromosomal abnormalities result in
miscarriage or stillbirth.
 50% of spontanous abortion are
chromosomal abnormal.
When to suspect it

 Unexplained infertility
 Multiple abortion >2
 Prior case of defective baby
 Presence of congenital anomalies
(mental retardation, multiple
congenital abnormalities,
dysmorphic features)
Chromosomal findings in early

40% apparently normal

60% abnormal:
Trisomy (47 chromosomes – one extra) 30%

45,X (45 chromosomes – one missing) 10%

Triploidy (69 chromosomes – three sets) 10%

Tetraploidy (92 chromosomes – four sets) 5%

Other chromosome anomalies 5%

(e.g. structural anomalies)
Classification of chromosomal anomalies
 Numerical (usually due to de novo error in meiosis)
Aneuploidy - monosomy
- trisomy
Polyploidy - triploidy

 Structural (may be due to de novo error in meiosis or

Translocations Inversions
Deletions Ring chromosome
Duplications Isochromosome

 Different cell lines (error in mitosis, post zygotic)

Most frequent numerical anomalies
in liveborn
Down syndrome (trisomy 21: 47,XX,+21)
Patau syndrome (trisomy 13: 47,XX+13)
Edwards syndrome (trisomy 18: 47,XX,+18)

Sex chromosomes
Turner syndrome 45,X
Klinefelter syndrome 47,XXY

All chromosomes
Triploidy (69 chromosomes)
Chromosome Number Abnormality
Aneuploidy (48, XXXX)
Chromosome Number Abnormality
Trisomy 21 (47, XX, +21)
Chromosome Structure

Translocation Deletion Inversion Isochromosome

Insertion Ring
Single Chromosome Disorders
1.Deletion - portions
of the chromosome
are lost (genetic
material is missing);
2. Duplication - genetic
material is present
3. Inversion - parts of
the chromosome
are flipped (genetic
material is “flipped”)
 Inversion may be classified into two types:
 Pericentric - include the centromere
 Paracentric - do not include the centromere
Inversions in natural populations

 In natural populations, pericentric inversions

are much less frequent than paracentric
 In many sp, however, pericentric inversions
are relatively common, e.g., in some
 Paracentric inversions appear to be very
frequent in natural populations of Drosophila.
Two Chromosome Disorders

• Genetic material is added from
another chromosome

when cells go through

meiosis, parts of the
chromosomes stick
together and switch
• Material is swapped with another
 Reciprocal translocation : It is produced
when two non-homologous chromosomes
exchange segments – i.e., segments
reciprocally transferred.
 Robertsonian translocation :
a particular type of reciprocal
translocation in which the break-points
are located at or close to the centromeres
of two acrocentric chromosome
Let’s see that up close!
A Robertsonian translocation of chromosomes 13
and 14, an end to end fusion of the two chromosomes
 Generally during gametogenesis the
homologous chromosomes of each pair
separate out (disjunction) and are equally
distributed in the daughter cells.
 But sometime there is an unequal
distribution of chromosomes in the daughter
 The failure of separation of homologous
chromosome is called non-disjunction.
 Mitotic non-disjunction: The failure of
separation of homologous chromosomes during
mitosis is called mitotic non-disjunction.
 It occurs after fertilization.
 Here, one blastomere will receive 45
chromosomes, while other will receive 47.
 Meiotic non-disjunction: The failure of
separation of homologous chromosomes during
meiosis is called meiotic non-disjunction
 Occurs during gametogenesis
 Here, one type contain 22 chromosome, while
other will be 24.
 Ring chromosome is formed when a
break occurs on each arm of a
chromosome leaving two sticky ends on
the central portion which reunite as a
 Isochromosome : loss one arm with
duplication of the other
 Mosaicism – refer to the presence of two
or more cell lines with different chromosome
compositions in an individual.
 Contoh karyotype : 46,XY/47,XY,+21

 Mosaicism occurs as a result of

chromosomal non-disjunction after

 The genetic changes is not carried by

parents, so the risk for recurrence of a child
with mosaicism is usually negligible.
1 cell zygote

1st mitotic division

nondisjunction mitotic

monosomy trisomy normal normal

Down Syndrome (Trisomy 21)
 Trisomy 21 (95 %) ---classic type
 Translocation type
 Mosaicism (more rarely, about 2%)

 Karyotype =
47,XX+21 or
Karyotype Trisomy 21:
Translocation Type

46, XY, t(14;21)(p;q) or 46, XX, t(14;21)(p;q)

Karyotype Trisomy 21 :


47,XY,+21/46,XY (40%)
Risk correlate with maternal age
• <25 y/o 1/1600 • 35 to 39 y/o 1/270
• 30 to 34 y/o 1/800 • > 40 y/o 1/80
Clinical features
 “Happy children”
 Mental retardation (mean IQ< 50)
 Developmental delay
 Hypotonia
 Signs of hypothyroidism
 Cardiac – CHD: PDA, VSD, ASD,
Atrioventricular Septal Defect
 Alzheimer-like dementia
 Leukemia
 Short lifespan
Craniofacial dysmorphology
 Microcephaly, brachycephaly
with relatively flat occiput
 Flat facial profile
 Short, up slanting palpebral fissures
 Small nose with flat nasal bridge;
 Brushfield, speckled spots of the iris
 Inner epicanthal folds
• Small mandible, small mouth
with protruding tongue
• Small ears with abnormal shape

•Short, broad hands

Flat facial profile • Stubby fingers
•Small nose with flat nasal bridge;
•Inner epicanthal folds
•Short, up slanting palpebral
The palm of patient with Down syndrome

crease simian


 Hypotonia 80%
 Poor Moro reflex 85%
 Hyperflexibiliry of joints 80%
 Excess skin on back of neck 80%
 Flat facial profile 90%
 Upslanted palpebral fissures 80%
 Abnormal auricles 60%
 Dysplasia of pelvis 70%
 Dysplasia of mid phalanx fifth finger (clinodactily) 60%
 Simian crease 45%
Trisomy 18
Edwards syndrome

 Incidence
 >90% dead in 1st
Trisomy 18
 Classic type : Karyotype 47, XY,+18
Trisomy 18
Edwards syndrome
 Weak cry
 Hypoplasia of skeletal muscle,
subcutaneous and adipose tissue.
 Severe Mental retardation and many
physical birth defects
 CHD, VSD, PDA and horseshoe kidney,
Trisomy 18 chromosome
Edwards syndrome

dysmorphism :

•Strawberry-shaped head
• Micrognathia (small
Small face with prominent
occiput (strawberry-shaped
Small sternum, small nipples
Edwards syndrome
• Overlap of second finger on third, fourth
finger on fifth
• Fixed finger contractures
Edwards syndrome

Hypogonadism - small penis,

Rocker-bottom feet
Trisomy 13
Patau syndrome

 severe birth
 mental
Trisomy 13
Patau syndrome
 Open scalp lesion, scalp defect
 Cleft palate (may be bilateral)
 Microcephaly
 Microphthalmos,coloboma of the eyes
 Malformed ears
 Polydactily
Patau syndrome
variable defect in facial development

Cleft palate
Polydactily of feet
Newborn boy with diagnosed
Patau syndrome (cleft lip and
palate, polydactyly of left hand,
atrial septal defect) Boy 5 yrs old with
Patau syndrome
(congenital deafness
and blindness)
Turner syndrome

 Affects
1 in 2500 newborn girls;
 One X chromosome is either missing or
 Types:
 Classic monosomy (60 %); karyotype: 45, X
 Structural abnormality (25 %) – the structure of one
of the X chromosomes is altered (deletion,duplication).
 Mosaicism (15 %)
Karyotype Turner Syndrome :
Classic Type
Karyotype :45, X
Turner Syndrome

Short Female,
Broad Chest with Wide Space of Nipples,
Congenital Lymph edema
Dysmorphic features
 shield-shaped chest,
 webbing of the neck, appearance of short neck
 low posterior hairline,
 Cubitus valgus (increased carrying angle, > 30 °)
 Short stature (height adult – 135 cm)
 Multiple pigmented nevi
 lymphedema of hands and feet at birth,

Webbing Neck Lymphedema

Turner syndrome

Short stature
Tendency to become obese
Klinefelter syndrome
Hypogenitalism and Hypogonadism. Long
Legs, Dull Mentality, and/or Behaviorals

 80 % - children with Klinefelter syndrome

have a male karyotype with an extra
chromosome X- 47,XXY
 20% - have multiple sex chromosome
aneuploidies (48,XXXY; 48,XXYY;
49,XXXXY), mosaicism (46,XY/47,XXY);

 20% of aspermic adult male (blocked

Klinefelter syndrome
 Puberty occurs at the normal age, but the testes
remain small.
 Patients develop secondary sex characters late;
 50% develop gynecomastia.
 They have taller stature.
 Patients with 46,XY/47,XXY have a better
prognosis for testicular function.
Deletion 5p syndrome
(cri-du-chat , cat’s cry syndrome)
The cause of this syndrome is a deletion of part of the short arm
of chromosome 5.
Del 5p14-p15
 Low birth weight (less than 2.5
 Slow growth-100%
 Cat-like cry-100%
 Mental deficiency-100%
 Hypotonia-78%
Deletion 5p syndrome
(cri-du-chat , cat’s cry syndrome)
Cat-like cry in infancy, microcephaly,
downward slant of the palpebral fissures
Deletion 5p syndrome
(cri-du-chat , cat’s cry syndrome)

 Children affected with this disorder have a

striking cat-like cry that is caused by
laryngeal hypoplasia.