GENETIC DISORDERS

(Pathophysiology)
Unit: I
Farman Ullah Khan
Bsn From KMU
Peshawar
 GENETICS
Genetics is the study of heredity, the passing of
genes from parents to their offspring through the
gametes.
Genes:
Are the basic units of inheritance and they
ultimately influence all aspects of body structure
and function.
DNA
It is a long molecule that is made up of thousand s
segments of genes.
 GENETICS
Chromosomes
chromosomes
are large
structures
made up
of DNA.
 GENETIC DISORDERS
Genetic disorders are the result of genes or
chromosomal alterations.
Mutation
A mutation is a permanent change in genetic
material. Some mutations results in serious
disorders.
 Single Gene disorders
 Multifactorial disorders
 Chromosomal disorders
 CHROMOSOME STRUCTURE

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 KARYOTYPE
A karyotype is an ordered display of chromosomes
arranged according to size. Karyotyping is done to
detect chromosome abnormalities.
• Total number is given first, followed by sex
chromosome complement & then description of
any abnormality.
• e.g a male with trisomy 21 is designated as:
47 x y + 21

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 Human Karyotype

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46,XY
 Genetic disorders
Single Gene Disorders
• The inheritance patterns are clear in single
gene disorders
Multifactorial Disorders
 Disorders caused by both genetic and
environmental factors are classified as
Multifactorial disorders

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 Genetic disorders
• Genetic disorders may be classified into three major
categories:
• Single-Gene Or Monogenic Disorders:
• Are caused by a single defective or mutant gene.
Most common types of single gene disorders are:
• Autosomal dominant (Marfan’s syndrome)
• Autosomal recessive (Pheny Ketonuria(PKU)
• Sex-Linked (x-linked) (Hemophilia, color blindness)

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 Multifactorial or Polygenic
Disorders
• Multifactorial disorders involves the interaction of a
number of genes with multiple environmental
factors.
• Coronary Heart Disease { Environmental

• Hypertension Factors }
• Diabetes mellitus
• Cleft lip or palate { Congenital disorders}
• Club foot
• enecephaly
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 Chromosomal Disorders
• Chromosome abnormalities are the leading
known cause of:
• Mental retardation
• Miscarriage
• Congenital malformation
• Major chromosome aberration occurs at
least 1 in 12 conceptions
• Number of live births affected by these
abnormalities is significant about 1 to 150.

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 EUPLOID

• Any exact multiple of haploid number of (n=23)

chromosome is called EUPLOID (eu=good or true).
Gamete (n) and normal somatic cell (2n) both are
euploid forms.
POLYPLOID:
• Chromosome numbers such as 3n (TRIPLOIDY) and
(4n) TETRAPLOIDY) are called polyploid. For
Example in triploidy a zygote may have three copies
of each chromosome.

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 Aneuploidy
• Cells that have extra chromosomes or
chromosomes missing are aneuploid. Two types of
aneuploidy are discussed below.
• Monosomy refers to a condition in which there is
one chromosome is missing. It is abbreviated 2N - 1.
For example, monosomy X is a condition in which
cells have only one X chromosome.

• A trisomy has one extra chromosome and is

abbreviated 2N + 1. Trisomy 21 is an example of a
trisomy in which cells have an extra chromosome
21.

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 Alterations in Chromosome
Number
Aneuploidy
A change in chromosome number is called
aneuploidy. The change can occur in either the
sex chromosomes or the autosomes

 Trisomy 21 (Down’s syndrome)

 Monosomy X (Turner’s syndrome)
 Polysomy X (Klinefelter,s syndrome)

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 Trisomy 21 (Down’s syndrome)
• A condition in which a cell contains three
copies of chromosome # 21.it occurs 1/1000
live births. its risk increases with maternal
age. Studies suggest that the abnormality
results from deterioration of the oocyte. The
basic pathology behind the syndrome is
nondisjunction

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 Down Syndrome
• It is characterized by mental retardation, an abnormal
pattern of palm creases, a flat face, sparse, straight hair, and
short stature. People with Down syndrome have a high risk
of having cardiac anomalies, leukemia, cataracts, and
digestive blockages.
• Life expectancy of Down syndrome individuals is in the
middle teens but some live much longer.
• The gene responsible for Alzheimer’s is on chromosome 21.
Down’s are at increased risk for developing Alzheimer’s.
• Down Syndrome is associated with maternal age. Older
women, particularly those older than 40, are more likely to
have a Down Syndrome child.

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 Maternal Age
• At 25 years, 17% of secondary oocytes may have
chromosomal abnormalities. At 40 years, up to 74%
may contain abnormalities.
• Spontaneous Abortion (Miscarriage)
• Two-thirds of all pregnancies are lost. These
miscarriages are called spontaneous
abortions.
• Genetic mutation causes an estimated 60% of these
spontaneous abortions.

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 Down’s
syndrome

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 Trisomy 21 (Down’s
Syndrome)
• Individuals with extra copies of chromosomes 21
develop Down Syndrome.
• They can survive to adulthood, but have significant
health problems and developmental delays and are
almost always mentally retarded.
• In general, absence of one of the autosomal
chromosomes leads to embryonic death, i.e.,
spontaneous miscarriage.

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 Trisomy 21 (Down’s
Syndrome)

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 CLINICAL PICTURE
• Slanting almond shaped eyes
• Protruding tongue
• Small open mouth
• Single transverse crease on the palm
• Small skull
• Flat nose bridge
• Small low set ears
• Small stature and short extremities
• congenital heart disease
• Low IQ(20%-50%)

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 Symptoms

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 Mosaic Down Syndrome

• Some of the cells of mosaic Down's sydrome

are trisomy 21 but others are normal.
• This is due to
nondisjunction that occurs during mitosis
(after fertilization).
• Mosaic Down Syndrome is likely to be less
severe because some of the cells are normal.

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 Down Syndrome
• A is the movement of a chromoso
translocation mal segment from one
chromosome to another nonhomologous
chromosome.
• Five percent of Down Syndrome cases
involve a translocation.
• The translocation often involves
chromosome 14.

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 Down Syndrome
• In the translocation
diagrammed below,
chromosome #21
has become fused
with chromosome
#14.

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 Monosomy X (Turner’s
Syndrome)
• A condition in which a cell contain only one
member of the chromosome pair in a diploid
cell or the presence of only one copy of a X
chromosome in a diploid cell. The syndrome
always found in females.1/2500 live births.

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 Sex Chromosome Aneuploidy
Monosomy X (Turner’s Syndrome)

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 Clinical Picture
• Short stature,but normal body proportions
• Widely spacednipples
• Absence of ovaries…
• No signs of secondary sex characteristics
• Nonpitting edema of the hands and feet.
• Coarctation of aorta
• Abnormal kidney location
• Infertile
• Normal IQ

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 (Turner’s Syndrome)

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 Polysomy X (Klinefelter,s
Syndrome)
• Is characterized by an X chromosome
positive in male .Most of the cases results
from nondisjunction during the first maternal
meiotic division 1/850 live births
• The syndrome always found in males

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 Klinefelter’s syndrome
• Extra copies of the sex chromosomes also
cause developmental errors, although the
effects are not fatal.
• Cases that result in an embryo with two X
and one Y chromosome (which geneticists
term XXY) develop Klinefelter syndrome: a
sterile male with many female body
characteristics. and, in some cases, mental
retardation.

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 Klinefelter’s syndrome

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 (Klinefelter’s Syndrome)
Clinical Picture
• Tall stature, but abnormal body proportion
• Latter in life body looks like female
• Deficient secondary male characteristics
• High pitch feminine voice
• Thin beard
• Infertile
• Normal IQ

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 XXX Females are normal

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XXXX and XXXXX females also exist
 Klinefelter syndrome, XXY

Male
Phenotype of syndrome
not apparent until
puberty
Breast development
Low fertility
Subnormal intelligence

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 Klinefelter’s syndrome
• An individual with three X chromosomes
(XXX) develops into a sterile female.
• Extra copies of the Y chromosome (XYY)
result in outwardly normal males. There is
some statistical indication that XYY men are
more likely to wind up in jail, suggesting an
impact on neuro cognitive development.

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 XYY Syndrome

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 Alterations in Chromosomes
structure

• Aberrations in chromosome structure occur

when there is break in one or more
chromosomes followed by rearrangement or
deletion of the chromosome parts:

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 Patterns of chromosomes
breakage & rearrangements
• Deletions
• Inversions
• Isochromosome formation
• Ring formation
• Translocations (centric fusion or
Robertsonian)
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 Structural Abnormalities
• When the chromosome's structure is altered. This can take
several forms:
• Deletions: A portion of the chromosome is missing or
deleted. Chromosome 5, Cri du chat syndrome ( Cry of the
cat). Low birth weight , Mental retardation.
• Duplications: A portion of the chromosome is duplicated,
resulting in extra genetic material. Mental retardation but
less serious physical defects.
• Inversions: A portion of the chromosome has broken off,
turned upside down and reattached, therefore the genetic
material is inverted. Balanced alterations.

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 Structural Abnormalities
• Translocations: When a portion of one chromosome
is transferred to another chromosome. The
Interchange of genetic material b/w
nonhomologous chromosomes.
• There are two main types of translocations. In a
reciprocal translocation, segments from two
different chromosomes have been exchanged.
• In a Robertsonian translocation, an entire
chromosome has attached to another at the
centromere. Long arm of two acrocentric
chromosomes join together.Confined to
chromosomes 13, 14, 15, 21, and 22.

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 Structural Abnormalities
• Rings: A portion of a chromosome has broken off
and formed a circle or ring. This can happen with or
without loss of genetic material.
• Most chromosome abnormalities occur as an
accident in the egg or sperm. Therefore, the
abnormality is present in every cell of the body.
Some abnormalities, however, can happen after
conception, resulting in mosaicism, where some
cells have the abnormality and some do not.
• Chromosome abnormalities can be inherited from a
parent (such as a translocation) or be "de novo"
(new to the individual). This is why chromosome
studies are often performed on parents when a
child is found to have an abnormality.
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 Changes
• Structural Numerical
• translocations – euploidy
• – inversions – aneuploidy
• – insertions
• – fusion

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 Factors causing
chromosomal breakage
include
• Exposure to radiation sources e.g. x-rays
• Influence of certain chemicals
• Extreme changes in the cellular environment
• Viral infections

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 THANK YOU

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