History

Genetics is the study of genes.

Inheritance is how traits, or characteristics,
are passed on from generation to
generation.
Chromosomes are made up of genes, which
are made up of DNA.
Genetic material (genes,chromosomes,
DNA) is found inside the nucleus of a cell.
Gregor Mendel is considered The Father of
Genetics"

Mendelian Genetics

Dominant traits- traits that are expressed.

Recessive traits- traits that are covered up.
Alleles- the different forms of a characteristic.
Punnett Squares- show how crosses are made.
Probability- the chances/ percentages that
something will occur.
Genotype- the types of genes (Alleles) present.
Phenotype- what it looks like.
Homozygous- two of the same alleles.
Heterozygous- two different alleles.

For each monohybrid cross, Mendel cross-fertilized true-breeding plants that

were different in just one characterin this case, flower color. He then allowed
the hybrids (the F1 generation) to self-fertilize.

Mendel studies seven characteristics in the garden pea

Statistics indicated
a pattern.

Chromosomes
Homologous chromosome: one of a matching pair of
chromosomes, one inherited from each parent.

Sister chromatids are identical

Law of Dominance
In the monohybrid cross (mating of two organisms that differ in only one
character), one version disappeared.

What happens when the F1s are crossed?

The F1 crossed
produced the F2
generation and the
lost trait appeared
with predictable
ratios.

This led to the

formulation of the
current model of
inheritance.

Alleles: alternative versions of a gene.

The gene for a particular inherited character resides at a specific locus
(position) on homologous chromosome.

For each character, an organism

inherits two alleles, one from each
parent

How do alleles differ?

Dominant allele
Recessive
allele

Recessive allele
Recessive allele

Dominant - a term applied to the trait (allele) that is expressed irregardless of

the second allele.
Recessive - a term applied to a trait that is only expressed when the second
allele is the same (e.g. short plants are homozygous for the recessive allele).

Probability and Punnett Squares

Punnett square: diagram showing the probabilities of the
possible outcomes of a genetic cross

Genotype versus phenotype.

How does a
genotype ratio differ
from the phenotype
ratio?

Punnett squares - probability diagram illustrating the possible

offspring of a mating.
Ss X Ss

gametes

Testcross
A testcross is designed to reveal whether an organism that displays the
dominant phenotype is homozygous or heterozygous.

Variation in Patterns of Inheritance

Intermediate Inheritance (blending): inheritance in which
heterozygotes have a phenotype intermediate between the phenotypes of
the two homozygotes

How Does it Work?

The Importance of the Environment

The environmental influences the expression of the genotype so the
phenotype is altered.
Hydrangea flowers of the same genetic variety range in color from blueviolet to pink, depending on the acidity of the soil.

Multifactorial; many factors, both

genetic and environmental,
collectively influence phenotype in
examples such as skin tanning

Pedigree analysis reveals Mendelian patterns in human inheritance

In these family trees, squares symbolize males and circles represent

females. A horizontal line connecting a male and female (--) indicates a
mating, with offspring listed below in their order of birth, from left to right.
Shaded symbols stand for individuals with the trait being traced.

Disorders Inherited as Recessive Traits

Over a thousand human genetic disorders are known to have Mendelian
inheritance patterns. Each of these disorders is inherited as a dominant or
recessive trait controlled by a single gene. Most human genetic disorders are
recessive.

A particular form of deafness is

inherited as a recessive trait.

Many human disorders follow

Mendelian patterns of inheritance
Cystic fibrosis, which strikes one
out of every 2,500 whites of
European descent but is much rarer
in other groups. One out of 25
whites (4% ) is a carrier.
The normal allele for this gene
codes for a membrane protein that
functions in chloride ion transport
between certain cells and the
extracellular fluid. These chloride
channels are defective or absent.
The result is an abnormally high
concentration of extracellular
chloride, which causes the mucus
that coats certain cells to become
thicker and stickier than normal.

Sickle-cell disease,
Sickle-cell disease is caused by the substitution of a
single amino acid in the hemoglobin protein of red
blood cells

Dominantly Inherited Disorders

Achondroplasia, a form of dwarfism with an incidence of one case among
every 10,000 people. Heterozygous individuals have the dwarf phenotype.
Huntingtons disease, a degenerative disease of the nervous system, is
caused by a lethal dominant allele that has no obvious phenotypic effect
until the individual is about 35 to 45 years old.

Sex-Linked Disorders in Humans

Duchenne muscular dystrophy, affects about one out of every 3,500 males
born in the United States. People with Duchenne muscular dystrophy rarely
live past their early 20s. The disease is characterized by a progressive
weakening of the muscles and loss of coordination. Researchers have traced
the disorder to the absence of a key muscle protein called dystrophin and
have tracked the gene for this protein to a specific locus on the X
chromosome.

Posture changes during

progression of Duchenne
muscular dystrophy.

Hemophilia is a sex-linked recessive trait defined by the absence of one or

more of the proteins required for blood clotting.

Color Blindness In Humans: An X-Linked Trait

Numbers That You Should See If You Are In One Of The Following
Four Categories: [Some Letter Choices Show No Visible Numbers]

Sex-Linked Traits:
1. Normal Color Vision:
A: 29, B: 45, C: --, D: 26
2. Red-Green Color-Blind:
A: 70, B: --, C: 5, D: -3. Red Color-blind:
A: 70, B: --, C: 5, D: 6
4. Green Color-Blind:
A: 70, B: --, C: 5, D: 2

Pattern Baldness In Humans: A Sex Influenced Trait

Baldness is an autosomal trait and is apparently influenced by sex hormones
after people reach 30 years of age or older.
In men the gene is dominant, while in women it is recessive. A man needs
only one allele (B) for the baldness trait to be expressed, while a bald woman
must be homozygous for the trait (BB).

What are the probabilities for the children for a bald man and
woman with no history of baldness in the family?

DNA
DNA is often
called the
blueprint of life.
In simple terms,
DNA contains the
instructions for
making proteins
within the cell.

Why do we study DNA?

We study DNA for
many reasons:
its central
importance to
all life on Earth
medical benefits
such as cures
for diseases
better food
crops.

Chromosomes and DNA

Chromosomes
are made up of
genes.
Genes are made
up of a chemical
called DNA.

The Shape of the Molecule

DNA is a very
long molecule.
The basic shape
is like a twisted
ladder or zipper.
This is called a
double helix.

One Strand of DNA

The backbone of
the molecule is
alternating
phosphate and
deoxyribose, a
sugar, parts.
The teeth are
nitrogenous
bases.

phosphate

deoxyribose

bases

The Double Helix Molecule

The DNA double
helix has two
strands twisted
together.
(In the rest of this
unit we will look
at the structure
of one strand.)

DOUBLEHELIX OF DNA

The Nucleus
DNA is located in the nucleus

Nucleotides

O
O -P O
O
O
O -P O
O

One deoxyribose together with

its phosphate and base make a
nucleotide.

O
O -P O

O
Phosphate

Nitrogenous
base

O
C
C

O Deoxyribose

The Basics Stucture

Each side of the ladder
is made up of nucleic
acids.
The backbone is a
phosphate and a sugar
The rung of the ladder
is the nitrogen base.

Hydrogen Bonds
When making
hydrogen bonds,
cytosine always
pairs up with
guanine,
And adenine
always pairs up
with thymine.
(Adenine and
thymine are shown
here.)

N
O

C C
N

Four nitrogenous bases

DNA has four different bases:

Cytosine
Thymine
Adenine
Guanine

C
T
A
G

Two Stranded DNA

Remember, DNA
has two strands
that fit together
something like a
zipper.
The teeth are the
nitrogenous
bases but why
do they stick
together?

Important
Adenine and Thymine
always join together
A -- T
Cytosine and Guanine
always join together
C -- G

Types of nitrogen bases

A= adenine
G= guanine
C= cytosine
T= thymine

Copying DNA
Step 1- DNA unwinds
and unzips
Step 2- Once the
molecule is separated
it copies itself.
The new strand of
DNA has bases
identical to the
original

DNA by the numbers

Each cell has about 2
m of DNA.
The average human
has 75 trillion cells.
The average human
has enough DNA to go
from the earth to the
sun more than 400
times.
DNA has a diameter of
only 0.000000002 m.

The earth is 150 billion m

or 93 million miles from
the sun.

Whats the main difference between DNA

and RNA

RNA
In RNA Thymine
is replaced by
Uracil
A-U (RNA)
not
A-T (DNA)

Transcription
When a secretary
transcribes a speech,
the language remains
the same. However,
the form of the
message changes
from spoken to
written

Transcription
Transcription- RNA
is made from a
DNA template in
the nucleus.
This type of RNA is
called messenger
RNA or mRNA

Transcription
DNA is protected
inside the nucleus.
mRNA carries the
message of DNA
into the cytoplasm
to the ribosome's

Translation
To translate English
into Chinese
requires an
interpreter.
Some person must
recognize the
worlds of one
language and
covert them into
the other.

tRNA Transfer RNA

The cells
interpreter
tRNA translated the
three-letter codons
of mRNA to the
amino acids that
make up protein.

Translation
Genetic translation
converts nucleic
acid language into
amino acid
language.

Codon
The flow of
information from
gene to protein is
based on codons.
A codon is a threebase word that
codes for one
amino acid

Codon

The flow of
information from
gene to protein is
based on codons.

Information Flow: DNA to RNA to Protein

Hereditaries Terminology
hereditary = derived from parents
familial = transmitted in the gametes through
generations
congenital = present at birth (not always genetically
determined - e.g. congenital syphilis, toxoplasmosis)
! not all genetical diseases are congenital - e.g.
Huntington disease - 3rd to 4th decade of life

Classification
3 groups of genetic diseases
1. Disorders with multifactorial inheritance
(polygenic)
2. Monogenic (mendelian) disorders
3. Chromosomal aberrations

1. Disorders with multifactorial

inheritance (polygenic)
influence of multiple genes + environmental factors
relatively frequent
Diabetes mellitus (see Endocrine pathology)
Hypertension (see Circulation)
Gout (discussed here + see Crystals)
Schizophrenia (Psychiatry)
Congenital heart disease - certain forms (see Heart)
Some types of cancer (ovarian, breast, colon) (see
Neoplasms)
often familial occurrence - probability of disease is in 1st
degree relatives about 5-10%; 2nd degree relatives - 0,5-1%

Gout
genetically impaired metabolism of uric acid (end
product of purine metabolism)
tissue accumulation of excessive amounts of UA
crystals
recurrent episodes of acute arthritis - precipitation of
monosodium urate crystals inside the joints
formation of large crystalline aggregates - tophi
chronic destruction of joints - joint deformity
renal injury
M>F

 Primary gout (90% of cases)

unknown enzymatic defect
Secondary gout (10%)
known cause of hyperuricemia (increased
turnover of nucleic acids - e.g. leukemias;
chronic renal disease; increased intake game, red wine)

Morphology
Acute arthritis
any joint, mostly hallux - abrupt and intense pain
reason??? - lower temperature?
Chronic arthritis
permanent precipitation - tophi - inflammation
(lymphocytes, histiocytes)
destruction of cartilage, fibrosis of synovial
membrane, ankylosis
Kidneys - 3 forms
medulla (papillae), tophi, kidney stones

 tophi are formed in the vicinity of joints, bursa olecrani, bursa

preapatellaris, auricle
less frequently kidneys, other tissues
urate crystals are soluble in water! - fixation in absolute alcohol
(biopsy!!!)
turns polarized light
patients with gout - obese, increased risk of hypertension,
arteriosclerosis
Clinical presentation - 3 stages
1. asymptomatic hyperuricaemia
2. acute arthritis - attacks of acute pain (days-weeks), silent
periods (months-years)
3. chronic changes - tophi, ankylosis, in 20% chronic renal
failure

2. Monogenic (mendelian) disorders

mutation of 1 gene, mendelian type of
inheritance
today about 5000 diseases
Autosomal dominant
Autosomal recessive
X-linked

Autosomal dominant disorders

both homozygotes and heterozygotes are
affected
usually heterozygotes (inherited from one
parent)
both males and females are affected
transmission from one generation to the other
50% of children are affected

Familial hypercholesterolemia
(= subgroup of hyperlipoproteinemia)
most frequent mendelian disorder - 1:500
mutation of gene encoding LDL-receptor (70% of plasma
cholesterol)
heterozygotes 2-3 elev. of plasma cholesterol levels
homozygotes 5 elevation of plasma cholesterol levels
heterozygotes asymptomatic until adulthood - xanthomas
along tendon sheets, coronary AS
homozygotes - xanthomas in childhood, death due to MI by
the age of 15Y

Marfan syndrome
French pediatrician Marfan - 1896 - young girl
with typical habitus
abnormal protein fibrillin - secreted by
fibroblasts, part of ECM
impairment of collagenous and elastic tissue decreased firmness of connective tissue
principal clinical manifestations - 3 systems

1. skeleton
slender, elongated habitus
long legs, arms and fingers (arachnodactyly) El Greco!
high, arched (Gothic) palate
hyperextensibility of joints
spinal deformities, pectus excavatum, pigeon
breast - pres. Lincoln???

2. ocular changes
dislocation or subluxation of the lens
(weakness of suspensory ligaments)

3. cardiovascular system
fragmentation of elastic fibers in tunica media
- aorta
aneurysmal dilatation - aortic dissection rupture (35-45% of pts.)
incompetence (dilatation) - aortic valve
tricuspidal and/or mitral valve - floppy valve

Ehlers-Danlos syndrome
similar to Marfan syndrome
genetic defect of collagen fibrils - several types
- both autosomal dominant and recessive
hyperextensibility of skin, hypermobility of
joints - contortionist!
joint dislocations, vulnerability
rupture of large vessels, colon, cornea

2. Autosomal recessive
majority of mendelian disorders
only homozygotes are affected, heterozygotes
(parents) are only carriers
25% of descendants are affected
if the mutant gene occurs with low frequency - high
probability in consanguineous marriages
onset of symptoms often in childhood
frequently enzymatic defect
testing of parents and amnial cells

Cystic fibrosis
1:2000 live births - most common lethal genetic
disease in white population
defect in the transport of chloride ions across
epithelia - increased absorption of Na+ and water to
the blood
widespread defect in the exocrine glands abnormally viscid mucous secretions
blockage of airways, pancreatic ducts, biliary ducts

 Pancreatic abnormalities (85%) - dilatation of

ducts, atrophy of exocrine part, fibrosis
Pulmonary lesions - dilatation of bronchioles,
mucus retention, repeated inflammation,
bronchiectasis, lung abscesses, emphysema and
atelectasis (100%), cor pulmonale chronicum
GIT - meconium ileus (newborns) (25%), biliary
cirrhosis (2%)
Male genital tract - sterility (obstruction of vas
deferens, epididymis, seminal vesicles) (95%)

Clinical symptomatology
recurrent pulmonary infections
pancreatic insufficiency, malabsorption syndrome
(large, foul stool), hypovitaminosis A, D, E, K, poor
weight gain
high level of sodium in the sweat - "salty" children mother's diagnosis
death usually in 3. decade due to respiratory failure

Phenylketonuria (PKU)
absence of enzyme phenylalanine-hydroxylase (PAH) Phe
>Tyr
increase of plasmatic Phe since birth - rising levels - impairs
brain development
after 6M - severe mental retardation - IQ under 50
decreased pigmentation of hair and skin - absence of Tyr
EARLY SCREENING TEST!!!
DIET!!!
mothers with PKU - increased levels of Phe - transplacental
transport - child with severe mental defect (although
heterozygous!) - maternal PKU - DIET!!!

Galactosemia

defect of galactose metabolism

lactose -> Gal+Glc
Gal -> Glc - defect - accumulation of Gal in blood
liver, eyes, brain are affected
hepatomegaly (fatty change - fibrosis - cirrhosis)
lens - opacification - cataracts
brain - loss of neurons, gliosis, edema
Symptomatology - from birth
vomiting, diarrhea, jaundice, hepatomegaly
later - cataracts, mental retardation
DIET!

Glycogen storage diseases

(glycogenoses)
deficiency of any one of the enzymes involved in
degradation or synthesis
depending on the type of defect - tissue distribution,
type of accumulated product
12 forms - most important:
type I. - von Gierke disease - hepatorenal type
type II. - Pompe disease - generalized type (liver,
heart, skeletal muscle)
type V. - McArdle syndrome - skeletal muscle only
biopsy: PAS, Best's carmine

Lysosomal storage diseases

defect of lysosomal enzymes, hydrolyzing
various substances (a.o. sphingolipids,
mucopolysacharides) - storage of insoluble
metabolites in lysosomes
extremely rare
Sphingolipidoses
more frequent in Ashkenazi Jews

Gaucher disease
defect of glucocerebrosidase - 3 types (type 1
- survival, type 2 - lethal, type 3 intermediate)
accumulation of glucocerebroside (Glcceramide) - kerasin
Gaucher cells - spleen (red pulp), liver
(sinuses), bone marrow

Niemann-Pick disease
defect of sphingomyelinase
accumulation of cholesterol and
sphingomyelin in spleen, liver, BM, LN, lungs massive visceromegaly
CNS (foamy cells) - severe neurological
deterioration
death during first 4-5 years

Tay-Sachs disease (gangliosidosis)

neurons and glial cells of CNS - mental
retardation, blindness

Mucopolysacharidoses
MP synthesized in the connective tissue by fibroblasts part of the ground substance
several clinical variants (I-VII)
involvement of liver, spleen, heart (valves, coronary
arteries), blood vessels
Symptoms: coarse facial features (gargoylism), clouding
of the cornea, joint stiffness, mental retardation
usually death in childhood (cardiac complications)
most frequent Hurler syndrome and Hunter syndrome
(X-linked!)

X-linked diseases
transmitted by heterozygous mother to sons
daughters - 50% carriers, 50% healthy
sons - 50% diseased, 50% healthy
Children of diseased father - sons are healthy, all
daughters are carriers
Hemophilia A (defect of Factor VIII)
Hemophilia B (defect of Factor IX)
Muscle dystrophy (Duchen disease)

3. Chromosomal aberrations
(cytogenetic disorders)
alternations in the number or structure of chromosomes
autosomes or sex chromosomes
studied by cytogenetics
cell cycle arrested in metaphase (colchicin) - staining by
Giemsa method (G-bands) - photographing - karyotype
2 sets of 23 chromosomes
22 pairs of autosomes, 2 sex chromosomes (XX or XY)
cytogenetic disorders are relatively frequent! (1:160
newborns; 50% of spontaneous abortions)

Numerical abnormalities
euploidy - normal 46 (2n)
polyploidy (3n or 4n) - spontaneous abortion
aneuploidy
trisomy (2n+1) - 47 - compatible with life
monosomy (2n-1) - autosomal - incompatible
with life

- sex chromosomal compatible with life

Structural abnormalities
breakage followed by loss or rearrangement
deletion, translocation
Generally:
loss of chromosomal material is more dangerous than
gain
abnormalities of sex chromosomes are better tolerated
than autosomal
abnormalities of sex chromosomes sometimes
symptomatic in adult age (e.g. infertility)
usually origin de novo (both parents and siblings are
normal)

Autosomal disorders
Trisomy 21 (Down syndrome)
most frequent - 1:700 births; parents have
normal karyotype
maternal age has a strong influence: <20 y.
1:1550 live births, >45 y. 1:25 live births
most frequently is abnormality in ovum (ovum
is under long-time influence of enviroment)

Clinical symptoms

mental retardation (IQ 25-50)

flat face + epicanthus
congenital heart defects
neck skin folds
skeletal muscle hypotonia
hypermobility of joints
increased risk of acute leukemias
mortality 40% until 10Y (cardiac complications)

Less frequent disorders

Trisomy 18 (Edwards syndrome) 1:8000
Trisomy 13 (Patau syndrome) 1:15000

Sex chromosomal disorders

a number of karyotypes from 45(X0) to 49
(XXXXY) - compatible with survival
normally - in females 1 of X is inactivated (all
somatic cells contain Barr body)
! male phenotype is encoded by Y

Klinefelter syndrome (47, XXY)

1:1000 males
additional X is either of paternal or maternal origin
advanced maternal age, history of irradiation of
either of parents
wide range of clinical manifestations
distinctive body habitus - increase length between
soles and pubic bone
reduced body and facial hair
gynecomastia
testicular atrophy - impaired spermatogenesis sterility (rarely fertility! - mosaics)

Turner syndrome (45, X0)

1:3000 females
primary hypogonadism in phenotypic female
growth retardation (short stature, webbing of
the neck, low posterior hairline, broad chest,
cubitus valgus)
streak ovaries - infertility, amenorrhea,
infantile genitalia, little pubic hair

Prenatal diagnostics
amniocentesis - analysis of amniotic fluid
cytogenetic analysis (karyotype - e.g. Down)
biochemical activity of various enzymes (e.g. TaySachs)
analysis of various specific genes (CF gene - PCR)
sex of the fetus (X-linked disorders - hemophilia)

Pediatric diseases
infants and children
first year of life - high mortality
highest mortality - neonatal period (first 4W;
perinatal first 1W)
between 1Y and 15Y of age - the leading cause
of death = injuries from accidents

Congenital malformations
structural defects present at birth - some may
become apparent later!
etiology is either genetic or environmental
viral infections (rubella, CMV) - during first 3M
other infectious (toxoplasmosis, syphilis, HIV)
drugs (thalidomide, alcohol, cytostatics)
irradiation
in 40-60% is the cause unknown!

Perinatal infections
ascending (transcervical) - in utero or
during birth (HSV, HIV)
transplacental - syphilis, toxoplasmosis,
rubella, CMV

Prematurity
higher morbidity and mortality than in full term babies
before 37.-38. W
high risk - weight <2500g
intracerebral bleeding (immature vessels in basal ganglia)
infant respiratory distress syndrome RDS - decrease in
surfactant synthesis; 15-20% 32.-36.W vs. 60% <28.W
SIDS - sudden infant death syndrome (crib death, cot
death)
Erythroblastosis fetalis - hemolysis due to ABO or Rh
incompatibility between mother and fetus

Tumors
benign vs. malignant
benign (hemangioma - nevus flammeus - port
wine stains, lymphangioma - hygroma colli
cysticum, sacrococcygeal teratoma)
malignant (hematopoietic - malignant
lymphomas, leukemias - see Hematopathology;
neurogenic (neuroblastoma, Ewing sarcoma,
primitive neuroectodermal tumor - PNET, CNSmedulloblastoma), sarcomas (rhabdo-, osteo-),
kidneys (Wilms' tu), thyroid (papillary ca)

 A congenital anomaly is a structural

abnormality of any type that is present at
birth.
Congenital anomalies may be induced by
genetic or environmental factors. Most
common congenital anomalies, however, show
the family patterns expected of multifactorial
inheritance (determined by a combination of
genetic and environmental factors).
About 3% of all liveborn infants have an
obvious major anomaly.
The incidence is about 6% in 2-year-olds
and 8% in 5-year-olds.
Congenital anomalies may be single or
multiple and of minor or major clinical
significance.

During the first 2 weeks of development,

teratogenic agents usually kill the embryo or
have no effect.
During the organogenesis period (3rd 8th
weeks), teratogenic agents disrupt
development and may cause major congenital
anomalies.
During the fetal period (9th week 9th
month) teratogens may produce
morphological and functional abnormalities,
particularly of the brain and eyes.

Causes of congenital anomalies

1-Genetic factors such as chromosomal
abnormalities and mutant genes.
2-Environmental factors e.g.: the
mother had German measles in early
pregnancy will cause abnormality in
the embryo.
3-Combined genetic and environmental
factors (mutlifactorials factors).

Types of abnormalities
1-Malformations: this occurs during the formation
of the structures of the organ (during
organogenesis) results in partial or complete non
formation or alterations in the normal structure.
This occurs in the 3rd to the 8th week of gestation.
Ex. Cleft lip and or cleft palate.
2-Disruptions: results in morphological change of
the already formed structure due to exposure to
destructive process. e.g.: vascular accidents
leading to intestinal atresia, amniotic band
disruption.
3-Deformations: due to mechanical forces that
affect a part of the fetus over a long period. Ex:
talipes equinovarus deformity.
4-Syndrome: is a group of anomalies occurring
together due to a common cause .

The genetic factors leading to congenital

anomalies may be due to chromosomal
abnormalities, gene mutations or may be
multifactorial.
Chromosomal abnormalities occur due to:
- late maternal age at the time of
pregnancy
(leads to chromosomal non-disjunction),
- radiation (causes chromosome deletions,
translocations or breaks),
- viruses as German measles,
- autoimmune diseases,
- and some chemical agents as antimitotic
drugs.

Chromosomal abnormalities are classified into numerical and

structural.

Numerical
chromosomal anomalies
are divided into:
1- polyploidy as triploidy ( a fetus
with 69 chromosomes) and
tetraploidy where the fetus has 92
chromosomes. Polyploidy leads to
severe congenital anomalies and
early abortion.

2- Aneuploidy (one or more chromosomes is added or

missed) as in:
Down syndrome (trisomy 21),

 Edward syndrome (trisomy 18),

Patau syndrome (trisomy 13),

 Turner syndrome ((45,X or a female missing one X), and

Klinefelter syndrome (47,XXY or a male person with an extra X
chromosome).

 Structural chromosomal anomalies

include
chromosomal deletion,
duplication,
translocation,
inversion,
ring and
iso chromosomes.

It may also lead to severe congenital

anomalies or fetal death.

Environmental factors
1) Infectious Agents:

1-Infectious agents include a number of viruses:

Rubella used to be a major problem. It causes
cataract, glaucoma, heart defects and deafness.
Cytomegalovirus :The infection is often fatal and if
not meningoencephalitis produce mental
retardation.
Herpes simplex, varicella and human
immunodeficiency viruses are other examples.
2- Toxoplasmosis
3- Syphilis : leads to congenital deafness and mental
retardation.

Environmental factors Cont.

2)Radiation :
Ionizing radiation kills rapidly proliferating cells, producing any
type of birth defect depending upon dose and stage of
development. Ex. Atomic bomb on Hiroshima and Nagasaki.
Exposure of the pregnant woman to a large dose of x- ray can
lead to microcephaly, spina bifida or cleft palate.

Environmental factors Cont.

3) Chemical agents:
There are many dangerous drugs, if have given to the
pregnant female, can produce congenital anomalies. Ex.:
- Thalidomide (antinauseant sleeping pills) produce limb
defects (phocomelia) and heart malformations.
- Diphenylhydantoin produce facial defects and mental
retardation.
Tetracycline (bone and teeth anomalies)
Aspirin may cause harm in large doses.
Cocaine cause birth defect possibly to its effect as a
vasoconstrictor that cause hypoxia.
Alcohol cause fetal alcohol syndrome.

Environmental factors Cont.

5)Hormones:
Androgenic agents (synthetic progestin to prevent
abortion) cause masculinization of the genitalia of
female embryos.
Endocrine hormones as Diethylstilbestrol cause
malformation of the uterus, uterine tubes, upper vagina,
vaginal cancer and malformed testes.
Insulin which treat diabetes of the mother congenital
anomalies.
Cortisone (in large doses) may cause cleft palate.

Environmental factors Cont.

6)Maternal Disease:
Diabetes cause variety of malformations as
heart and neural tube defects.
7)Nutritional deficiency: particularly vitamins
deficiency.
8)Heavy metals: Eg: organic mercury.

PRENATAL DIAGNOSIS
Methods of prenatal diagnosis are divided into invasive and non-invasive
techniques.
Technique
Time
Disorders diagnosed
(in weeks)
A. Non-invasive:
Maternal serum screen:
Alpha feto protein (AFP)
16
Neural tube defects (NTD)
Triple test
16
Down syndrome
Ultrasound
18
Structural defects in many
organs as CNS, heart,
kidney, and limbs.
B. Invasive:
- Amniocentesis

14-16

- Chorionic villus sampling

- Fetal blood sample

10-12
near term

Chromosomal and metabolic

abnormalities, and DNA
analysis.
As amniocentesis.
As amniocentesis + blood
disorders.

Technique of amniocentesis

Technique of CVS

U/S showing polydactyly

U/S showing micrognathia

U/S showing Umibilical hernia (associated with Trisomy 18 in 50% of cases)

Fetal therapy
The fetus during intrauterine life can receive treatment such as:
1- Fetal transfusion (administration of blood transfusion to the
anemic fetus in thalassemia).
2- Medical treatment of thyroid dysfunction or congenital adrenal
hyperplasia of the fetus.
3- Fetal surgery: is possible due to advanced ultrasound and surgical
procedures eg: repair of hernia of the fetus or in case of
hydrocphalus.
4- Stem cell transplantation (adults, in TDC Surabaya) and gene
therapy: it is possible to transplant stem cells before 18 weeks of
gestation of the fetus without rejection because the
immunocompetence of the fetus doesnt develop yet.