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Teratology (PowerPoint)

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					      Basic Medical Education Programme
              School of Medicine
          Gadjah Mada University


 CONGENITAL MALFORMATIONS,
TERATOLOGY, HERMAPHRODITISM




                                          1
                      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
   CM

HERMAPHRODITISM
  Errors in sex development may result in
   various degree of intermediate sex
                                         3
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)
                                                    4
     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
                                                5
              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 Turner’s syndrome or
    ovarian dysgenesis
                                          6
2. TRISOMY
       If three chromosomes are present instead of the
        usual pair
       Cause of trisomy is non disjunction during
        meiosis
       Autosomal trisomy
         21 trisomy (Down’s syndrome) 1 : 600
         18 trisomy (Edwards’s syndrome) 1 : 3300
         13 – 15 trisomy (Patau’s 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          7
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                                 8
5. POLYPLOIDY
  Polyploid cells contain multiple of
   the haploid number of chromosomes
   (I.e : 69, 92)
  A significant causes of spontaneous
   abortion


                                     9
               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                       10
              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
  polydactyly; recessive: congenital adrenal
  hyperplasia, microcephaly, and
  dentinogenesis imperfecta                 11
                        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
                                                  12
      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


                                            13
14
   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.
                                                 15
     TERATOGEN                  MALFORMATIONS
Androgenic Agents
 Ethisterone        Varying degrees of masculinization of
 Nonethisterone     female fetus ; most have labial fusion
                     and clitoral hypertrophy
Antitumor Agents
 Aminopterin        Wide range of skeletal defect and
                     malformations of the CNS
   Busolfan         Stunted growth, skeletal abnormalities
    (Myleran) G –    corneal opacities, cleft palate
    mercaptopurine
                     hypoplasia of various organ
   Methotrexate     Multiple malformation, especially
                     skeletal

Thalidomide          Meromelie and other limb
                     malformations, external ear, cardiac16
                     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 chorioretinitis

Therapeutic Radiations   Microcephaly and skeletal
                         Malformation
                                                        17
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.

                                           18
Cellular Sites of Action of Various Dysmorphogenic Drug
                                                     19
       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

                                               20
                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
                                                  21
Differential diagnosis of persons with ambiguous external genitalia 22
  Origin of the         Normal                   Abnormal
  malformation          development              development

                                                 Dominant or
Point mutation              Genetic              recessive defect
Chromosomal               information
                                                 Syndrome of
aberration                                       chromosomal
                                                 aberration
         Placenta of
         mother
                       Organogenesis       Important defects
Exogenous and
multifactorial
actions                                 Metabolic            Malformations
                          Fetus         anomalies
                                        genital system
                                        nervous system

                       Normal neonate                    Malformed neonate
                                                                     23