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RECURRENT ABORTIONS AND

CHROMOSOMAL DEFECTS
Chrysantine Paramayuda, Hannie D. Kartapradja, Debby D.
Ambarwati, Shirley Renatha, Faiza Az Zahra, Iswari Setianingsih, Alida
R. Harahap, Nanis S. Marzuki

Eijkman Institute for Molecular Biology, Jakarta, Indonesia

PIT FETOMATERNAL 16
Manado, 9-11 March 2015

INTRODUCTION
Recurrent pregnancy loss or recurrent abortion is defined as
two or more consecutive spontaneous abortions.
15%-20% of clinically recognizable pregnancies end in
spontaneous abortion in the first-trimester
At least 50% -60% result from a chromosomal abnormality.
The chromosomal abnormalities found in the abortus could
occur spontaneously (de novo) or inherited from one of the
parents and may be correlated with maternal age.

Farcas et al. (2007); El-Dahtory FAM. (2011) ; Dubey et al. (2005)

AIM OF THE STUDY

To report wide variations of chromosomal
abnormalities in recurrent abortions cases
that were referred to Cytogenetics unit at
Eijkman Institute during the year 2010 -
2014

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METHODS CYTOGENETICS
GTL-Banding & Karyotyping
Sample: POC ( mostly chorionic villi)

MOLECULAR
GENETICS
Interphase FISH

RESULTS AND DISCUSSIONS

POC samples (n= 151)
126 abortions (83.4%) occured during 1st trimester
Maternal age: 25-46 years
Gestational age: 5 to 32 weeks
Up to 10 times of abortions

CHROMOSOME ANALYSIS
Karyotyping (n=143)
FISH (n = 4)
Karyotyping and FISH (n= 4)

Chromosomal abnormalities
(79 samples/ 52.3%)

Distribution of Chromosomal
Abnormalities in Recurrent
Abortions (n=79/151)
8.9% Autosomal trisomies
14%
Polyploidy
58.2%
18.9%
Sex chromosomal
abnormalities
Autosomal structural
abnormalities

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Distribution of Autosomal Aneuploidy

(n= 46/79, 58.2%)
28.3
Frequency (%)

30.0

20.0
13.0 11.0
8.8
10.0 6.5 6.5
4.3 4.3
2.2 2.2 2.2
0.0

Chromosome Abnormality

Distribution of Polyploidy
( n= 15/79,18.9%)
20 15.3
Incidence (%)

13.3
15
10 6.7 6.7 6.7 6.7 6.7
5
0

Chromosome Abnormality

Distribution of Sex Chromosome

Aneuploidy
(n= 11/79, 14%)
63.6
Incidence (%)

80
60 27.3
40 9.1
20
0
Monosomy Mosaic 46,X,+21
X monosomy
X

Chromosome Abnormality

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Numerical Abnormalities
Autosomal aneuploidy is the result from errors (non-disjunction)
at meiosis I, specifically maternal meiosis I
Errors at both meiosis I and II are associated with maternal age
De novo

Recurrence risk is thought to be 1%,

Parental karyotype may not be necessary

Distribution of structural abnormality

(n=7/79, 8.9%)
Karyotype No./total of cases

mos
47,XX,inv(7)(q.11.23.q22),+9[37]/48,XXX,inv(7)(q11.23q22),+9[1]/46,XX,inv(7)(q1 1/7
1.23.q22)[2]
46,XX,inv(5)(q22q23) atau 46,XX,?add(5)(q22) 1/7
47,XY,t(12;19)(p12;p12),+15 1/7
46,XX,inv(20)(p13q12)
Inversions
1/7
mos (3/7, 49%)
47,XX,+mar[4]/47,XX,chrb(2)(q10)[1]/46,XX,t(9;12)(q22;p12)[1]/46,XX,del(3q)[1 1/7
]/46,XX,del(4p)[1]/46,XX,del(16q)[1]/46,XX[31]
46,XX,add(4)(q34) 1/7
46,XX,del(13)(q21) 1/7

Abbreviations: mos: mosaic, inv: inversion, mar: marker, chrb: chromosome break,del:
deletion, add: addition

Autosomal structural abnormalities

(n=7/79, 8.9%)
Structural chromosome abnormalities were responsible for about 5-10%
of early miscarriages (Farcas et al, 2007)
Autosomal structural abnormalities occured in approximately 3% of
cytogenetically abnormal abortuses (Chaithra., et al, 2011) .
Inversion, although relatively rare, can be associated with
congenital malformations and mental retardation, as well as
spontaneus abortion (Chaithra et al., 2011)
About 6-7% of couples with at least two spontaneous abortions, one
parent carries a balanced chromosome rearrangement (Farcas et al., 2007;
El-Dahtory et al., 2011) PARENTAL KARYOTYPING

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Mechanism of inv(20)(p13q11.2) in
the mother and fetus
p13 p13
p13 break
p12 p12 centromere p11.1
p p11.2 p11.2
p11.2
p11.1 p12
centromere p11.1
q11.2 break q11.2
q q11.2

Chromosome 20 inv(20)(p13q11.2)
normal
Breakage
Source: idiogram chromosome 20
from ISCN 2013 at ~450- band level

Distribution of maternal age

and gestational age
Range of Range of Mean
Chromosome Mean maternal
maternal age gestational age gestational age
Abnormalities age (years)
(years) (weeks) (weeks)

Autosomal aneuploidy 28-42 36.6 6 -13 9.6

Polyploidy 25-39 31 7 -11 9

Sex chromosomes
22-41 32 6-12 8
aneuploidy

Structural abnormalities 24-45 35 8-24 11

Conclusions
Chromosomal abnormalities (52.3%)
Autosomal trisomies were the most common chromosomal
aberration found (58.2%), with trisomy 22 as the most frequent
aneuploidy.
Structural abnormality (about 9%)
May be inherited from balanced parental chromosomal aberration.
This warranted for further parental chromosome investigation.
There is a likelihood of trisomic conceptus and structural
abnormalities increases with maternal age.
Genetic counselling.

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THANK YOU

DOKTER OBSTETRI &

GINEKOLOG
KLINIK
LABORATORIUM
RUMAH SAKIT
YAYASAN GENNEKA

Inversions
Paracentric and pericentric inversion arise in mitotic and
phenotypically normal.
But if they arise in precursors of the gametes, they may produce
abnormal genomes as they progress through meiosis
Pericentric Inversion
Paracentric Inversion
A

Distribution of Chromosomal
Abnormality and Frequency of Abortion
Chromosome Abnormalities
Range of number
of abortions Mean number of
(times) abortions (times)
Autosomal aneuploidy 2-9 2.8
Polyploidy 2-5 2.8
2-5 2.9
Sex chromosomes aneuploidy
Structural abnormalities 2-3 2.4

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Case: Mother and aborted fetus with

inv(20)(p13q11.2)
Maternal age: 31 yrs
No. of abortus: 3 x

Carp et al., 2006:

10 of 39 abortuses had balanced translocation or inversion identical to the parents.
Because the parents were phenotypically normal, hence these abortions must have
alternative cause.

Mechanism of Paracentric and

Pericentric Inversions

Mechanism of Paracentric Inversion

p21
p p21 break p21
p12
p13 memutar p13
centromere p12
p11 break p11 p11

kromosom 9 Posisi terjadinya patah inv(9)(p11p21)

normal
Sumber: idiogram kromosom 9
dari ISCN 2013 pada ~550- band level

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Mechanism of Pericentric Inversion

p15.3
p15.1 p15.3
patah
p15.1
p p14 q12
memutar
sentromer
q12 p14
patah
q13
q13

q35
q35

Kromosom 5 Posisi terjadinya patah Inv(5)(p15.1q13)

normal
Sumber: idiogram kromosom 5
dari ISCN 2013 pada ~450- band level

Maternal Age and Gestational Age

Development of those embryos with autosomal trisomies
arrested between 7-13 weeks of gestational age (mean: 9.6
weeks), whereas those with structural abnormalities aborted
at later gestational age (mean: 11 weeks).
Our study showed that autosomal aneuploidy and structural
abnormalities occured in later maternal age.This indicates
that the corelation with maternal age should be further
studied.

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1 kasus dengan keguguran 10x G..P..A..

Karyotyping Normal. Kemungkinan Parasit?.
Pemeriksaan parasitologi?.

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Autosomal Aneuploidy
Autosomal Aneuploidy
(n= 46/79, 58.2%)
Karyotype Incidence (%)
Trisomy 22 13/46 (28.3)
Trisomy 21 6/46 (13)
Trisomy 20 1/46 (2.2)
Trisomy 18 3/46 (6.5)
Trisomy 16 5/46 (11)
Trisomy 15 3/46 (6.5)
Trisomy 14 2/46 (4.3)
Trisomy 13 1/46 (2.2)
Trisomy 10 2/46 (4.3)
Trisomy 5 1/46 (2.2)
Trisomy 4 1/46 (2.2)
Trisomy 3 1/46 ( 2.2)
Mosaic trisomy 22 1/46 (2.2)
Mosaic trisomy 18 1/46 (2.2)
Mosaic trisomy 14 1/46 (2.2)
Mosaic trisomy 10 1/46 (2.2)

Mosaic double trisomy 13 and 21/XX/XXX 1/46 (2.2)

Double trisomy 21 1/46 (2.2)
Double trisomy 15 and 16 1/46 (2.2)

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