Basic Medical Education Programme

School of Medicine

Gadjah Mada University

CONGENITAL MALFORMATIONS,
TERATOLOGY,
HERMAPHRODITISM
dr. E. Suryadi, SU
SCHOOL OF MEDICINE GMU

INTRODUCTION
CONGENITAL MALFORMATION (CM) :
Are anatomical abnormalities
present at birth
May be macroscopic or microscopic
On surface or within the body
2

TERATOLOGY
Is the branch of embryology which
deals with abnormal development and
Congenital Malformation

HERMAPHRODITISM
Errors in sex development may result in
various degree of intermediate sex
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EPIDEMIOLOGY AND CAUSES OF CM

About 15% of deaths in neonatal period are
attributed to CM
About 6% of one year old infant have CM

3 CAUSES
1. Genetic factors : chromosomal abnormalities and
mutant genes
2. Environmental factors
3. Combination or interaction the genetic factors and
environmental factors (multifactor)
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CHROMOSOMAL
ABNORMALITIES

About one of 200 new born infants

Two kinds of changes : numerical and

structural
Changes in chromosome number represent
either aneuploidy or polyploidy
Aneuploidy, any deviation from the diploid,
may be hypodiploid or hyperdiploid
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NUMERICAL
CHROMOSOMAL
ABNORMALITIES
1. MONOSOMY
Embryos missing a chromosome usually
die
About 97 % at Embryos lacking a sex
chromosome also die and 3% (about 3 in
10.000 new born female) have
characteristics of Turners syndrome or
ovarian dysgenesis
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2. TRISOMY

If three chromosomes are present instead of the

usual pair
Cause of trisomy is non disjunction during
meiosis
Autosomal trisomy
21 trisomy (Downs syndrome) 1 : 600
18 trisomy (Edwardss syndrome) 1 : 3300
13 15 trisomy (Pataus syndrome) 1 : 5500

Sex chromosomal trisomy

47, XXX female 1 : 1000 mentally retarded
47, XXY Male 1 : 500 klinefelter syndrome
47, XYY Male 1 : 1000 personality disorder

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3. TETRASOMY AND PENTASOMY

Have four or five sex chromosome mental

retardation and physical impairment

4. MOSAICISM

Person with this condition have two or more cell

lines with different karyotypes (46 XX / 45 x 0 / 47
XXX)

The autosomes and the sex chromosome may be

involved

Usually the malformation are less serious

Usually arises by non disjunction during early

cleavage division

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5. POLYPLOIDY
Polyploid cells contain multiple of
the haploid number of chromosomes
(I.e : 69, 92)
A significant causes of spontaneous
abortion

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CHROMOSOMAL
STRUCTURAL
ABNORMALITIES
Result from chromosome breaks
Induce by various environmental factors
The type of abnormality which result depends
upon what happens to the broken piece
Kind of structural abnormalities
- Translocation

- duplication

- deletion

- isochromosome

- a ring chromosome

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MALFORMATION CAUSED BY
MUTANT GENES
Rarer than numerical and structural
chromosomal abnormalities
Most mutant genes do not causes CM to
express depend on dominant or recessive
gene
Examples, dominant: achondroplasia and
poldactyly; recessive: congenital adrenal
hyperplasia, microcephaly, and
dentinogenesis imperfecta

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MALFORMATION CAUSED BY
ENVIRONMENTAL FACTORS
Teratogen is agents may induce CM when
structures are developing
Kinds of teratogen
1. Variety of chemical : poisons, drugs,
industrial dyes
2. Infectious agent : rubella, toxoplasmosis,
rickettsia
3. Physical factors : like X-rays and anoxia
4. Mechanical factors : the amnionic fluid
absorbs mechanical pressures
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SENSITIVE OR CRITICAL
PERIODS
During the organogenesis period (from day
15 to day 60)
This period teratogenic agent may be lethal
or to produce major morphological
abnormalities

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The teratogenic effect of medications varies

temporally. That is, the fetus' susceptibility
varies depending on the fetus' apposite
critical periods of development.
Different organs have different critical
periods, although the interim from gestation
day 15 to day 60 is critical for many organs.
The heart is most sensitive during the third
and fourth weeks of gestation, while the
external genitalia are most sensitive during
the eighth and ninth weeks.
The brain and skeleton are always sensitive,
from the beginning of the third week to the
end of pregnancy and the neonatal period.
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TERATOGEN
Androgenic Agents
Ethisterone
Nonethisterone

Antitumor Agents
Aminopterin

Busolfan
(Myleran) G
mercaptopurine

Methotrexate

Thalidomide

MALFORMATIONS
Varying degrees of masculinization of
female fetus ; most have labial fusion
and clitoral hypertrophy
Wide range of skeletal defect and
malformations of the CNS
Stunted growth, skeletal abnormalities
corneal opacities, cleft palate
hypoplasia of various organ
Multiple malformation, especially
skeletal
Meromelie and other limb
malformations, external ear, cardiac
and gastrointestinal malformations 20

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Infectious Agents

Cytomegalovirus

Microcephaly, hydrocephaly
microphthalmia, microgyria and
mental retardation

Rubella virus

Cataract, chorioretinitis, deafness

microphtalmia and congenital
heart defects

Toxoplasma gondii

Therapeutic Radiations

Microcephaly, microphthalmia,
hydrocephaly and chorioretinitis
Microcephaly and skeletal
Malformation
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Three components of typical

teratogenic exposure leading to
CM

Hereditary predisposition to a
malformation
Hereditary predisposition to the effects
of a given teratogen ( genetic
susceptibility)
Administration of the teratogen at a
vulnerable period embryogenesis.
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Cellular Sites of Action of Various Dysmorphogenic Drug

SIX MECHANISM THAT

CAN CAUSES
CM (PATTEN)

1. Too little growth

2. Too little resorption

3. Too much resorption
4. Resorption in the wrong location
5. Normal growth in abnormal position
6. Local overgrowth of a tissue or structure
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HERMAPHRODITISM
= Intersexuality
Early embryo has the potential to develop into
a male and female
Classification :
True hermaphrodites
-have both ovarian and testicular tissue
Pseudo hermaphrodites
-have testes called male pseudohermaphrodites
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have ovaries called female pseudohermaphrodites

Differential diagnosis of persons with ambiguous external genitalia 27

Origin of the
malformation
Point mutation
Chromosomal
aberration
Placenta of
mother
Exogenous and
multifactorial
actions

Normal
development
Genetic
information

Organogenesis

Fetus

Normal neonate

Abnormal
development
Dominant or
recessive defect
Syndrome of
chromosomal
aberration
Important defects
Metabolic
anomalies
genital system
nervous system

Malformations

Malformed neonate
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