CONGENITAL MALFORMATIONS,

TERATOLOGY,
HERMAPHRODITISM

BY E. SURYADI
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

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

HERMAPHRODITISM
Errors in sex development may result in
various degree of intermediate sex

EPIDEMIOLOGY OF CM
Annually, approximately 3-5% of live births are
born with CM/birth defects.
Medications are uncommon causes, accounting for
1-3% of CM/birth defects.
About 6% of one year old infant have CM
About 15% of deaths in neonatal period are
attributed to CM

3 CAUSES of CM
1. Genetic factors : chromosomal
abnormalities and mutant genes
2. Environmental factors
3. Combination or interaction the genetic
factors and environmental factors

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

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

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

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

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

2. TRISOMY

If three chromosomes are present instead of the

usual pair
Cause of trisomy is non disjunction during
meiosis of gamet cells
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

11

12

Trisomy 18

13

Trisomy 13

14

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

Microdeletion or microduplication
syndromesChromoso Parental
Syndrome Clinical features
me findings origin
Prader-willi

Hypotoni, hypogonadism, short

stature, small hands and feet,..

Del 15 q12

Paternal

Angelmans

Microcephaly, ataxia, severe mental

retardation,..

Del 15 q12

Maternal

DiGeorge

Thymic and parathyroid hypoplasia,

del 22 q11
cardiac defect, facial dysmorphism,

Either parent

Velocardialfa
cial

Palatal defects, hypoplastic alae nasi, Del 22 q11

cardiac defects, speech delay,..

Either parent

SmithMagenis

Brachycephaly, prominent jaw, short

broad hands, mental retardation.

Either parent

Williams

Short stature, Hypercalcemia, cardiac Del 17 q 11,23

anomalies, mental retardation,..

Either parent

BeckwithWiedemann

Macroglossia, omphalocele,
hemihypertrophy, hypoglycemia,

Dup 11 p15

Paternal

Miller-Dieker

Dysmorphic face, seizures, severe

developmental delay, cardiac
anomalies,

Del 17 p13.3

Either parent

Del 17 p11.2

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

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

SENSITIVE OR CRITICAL PERIODS

During the organogenetic period (from day
13 to day 60 after conception)
This period teratogenic agent may be lethal
or to produce major morphological
abnormalities

TERATOGEN
MALFORMATIONS
Androgenic Agents
Ethisterone
Varying degrees of masculinisation of
Nonethisterone
female fetus ; most have labial fusion
and clitoral hypertrophy
Antitumor Agents
Aminoplerin
Basulfan
(Myleran) G
mercaptopurine
Methotrexate
Thalidomide

Wide range of skeletal defect and

malformations of the CMC
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

Infectious Agents
Cytomegaloviruse

Microcephaly, hydrocephaly
microphthalmia, microgyria and
mental retardation

Rubella virus

Cataract, chorioretinitis, deafness

microphtalmia and congenital heart
defects

Toxoplasma gondii

Microcephaly, microphthalmia,
hydrocephaly and chorioretnitis

Therapeutic Radiations Microchepaly and skeletal

malformation

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

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
have ovaries called female pseudohermaphrodites

Normal
development

Origin of the
malformation
Point mutation
Chromosomal
aberration

Genetic
information

Placenta of
mother
Exogenous and
multifactorial
actions

Organogenesis

Fetus

Normal neonate

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

Malformations

Malformed neonate

Some cases of birth defect

Small intestinal atresia/stenosis
Defect of neural tube
Spina bifida
Anencephali
Encephalocele
Orofacial cleft
Cleft palate
Cleft lip
Congenital heart defect
ASD
VSD
Tetralogy of Fallot

Prenatal diagnostic
USG examination
Amniocentesis
Villi-chorion biopsy

Prevention

Marriage counseling
Prenatal counseling and diagnostic
Education
Consume folic acid
Eat a healthy diet
Exercise regularly
Avoid smoking
Avoid alcohol
Avoid illicit drugs