Genetic Disorders

By Dr. Tesfaye H (MD, Pathologist)

1
 Continued…
• Contents:
1. Introduction
2. Mutation
3. Categories of Genetic Disease
4. Diagnostic Approach
5. Genetic Counseling
 1. Introduction
• Human genome project- about 100,000
genes.
• All diseases involve changes in gene
structure or expression.

• DNA and RNA microarrays- analysis of

human diseases.
• Two classes of genes- Structural(Protein
coding) &Regulatry genes
 1.1. Human Genetic Make up.
• Genome

• Chromosomes

• DNA+ Histone

• dNT

• Bases + Deoxyribose sugar + Phosphates

• A, G, T, C
The Cell
 Nucleus

ODNA: arranged in chromosomes

(network of granules = nuclear
chromatin)
O RNA: spherical intra nuclear
structure(s)
nucleolus / nucleoli
DNA structure
DNA
Continued…
 1.2. Terminologies
• Chromosomes- DNA + Histones forming
thread like structures in the nucleus.
• DNA- The store of genetic information.

• Gene- A segment of DNA sequences on the

chromosome that codes for protein.
• gene Locus: specific site of a gene on the
chromosome. Since the chromosomes
exist in pairs, genes are also paired.
Continued…
 chromosomes
Composed of double coils of DNA which Exist
in pairs – homologous: 22 autosomal + 1sex
chromosomes

Genes- specific base sequences in the

chromosome which code for specific information's

12
 Sex chromosomes
O Genetic sex = composition of X and Y
O Large X: many genes, many activities
O Small Y: almost entirely male sexual
differentiation.
O Female: XX, male XY
O One X randomly inactivated and
nonfunctional after first week of embryonic
development
O Same inactivated X in descendant cells
karyotype

14
Gene locus
• 23 paired
chromosomes
• P&Q arms (short
&long)
• Regions , 1,2 or 3
• Bands
• Sub bands
• e,g
12q22,1

15
Alleles: alternate forms of a gene can
occupy the same locus (homozygous,
heterozygous)
Recessive gene: expressed only when
homozygous
Dominant gene: expressed whether
homozygous or heterozygous,
both expressed when co-dominant
Sex-linked gene: only X-linked in males,
most are recessive, homozygous (no
allele on Y) 16
 Genome
O Sum total of all genes contained in a
cell’s chromosomes
O Identical in all cells
O Not all genes are expressed in all cells
O Not all genes are active all the time
O May code for enzymes or other
functional proteins, structural proteins,
regulators of other genes
 Human Genome
O 3 billion+ pairs of DNA nucleotides
O ~ 50,000 – 100,000 genes
O Protein-coding Genes = <10% of human genome
O Exons: parts of the DNA chain that code for
specific proteins
O Introns: the parts in-between the exons
O Both exons and introns are transcribed but only
the exons are translated (introns are removed from
mRNA before leaving nucleus)
O”Junk DNA”: no obvious function but 80%
expressed
Central dogma

19
mRNA and t RNA
21
 Continued…
• Hereditary(familial) or Genetic disorders-
Derived from one's parents, transmitted
in the gametes through the generations.

• Congenital- Born with(just present at

birth )
– may be genetic or not.
 2. Mutation
• Permanent changes in the DNA.
• Are the bases of genetic diseases.

• Can occur
Spontaneously during cell division.
Induced by mutagens (Radiation, infections &
chemicals)
 Continued…
• Can affect
Germ line cells (ovum and gametocyte)-
genetic disease.

Somatic cells- may cause cancer and some

congenital diseases.
Embryonic cells- mosaicism
 Classification of mutations
1) Genome mutation – loss or gain of whole
chromosome (monopsony, trisomy)
e.g. 47,xy, 45,xy
2) Chromosome mutation – rearrangement of
genetic material & give rise to visible
structural changes in chromosome
3) Gene mutation – majority of mutation with
hereditary disease

25
 Gene mutation
– Results in partial or complete deletion
of gene, more often affect single gene
– has three types
A. point mutation
B. deletion and insertion
C. tri nucleotide repeat mutations

26
 A, Point mutations
• result from the substitution of a single nucleotide
base by a different base, resulting in the
replacement of one amino acid by another in the
protein product
types of point mutation
– Missense mutations
– nonsense mutations
– Silent mutations
 Missense mutation
• Change in single base pair results in
changing the amino acid
– If biochemically similar to the original,
=>called a “conservative” missense mutation.
– “nonconservative” missense mutation
=>replaces the normal amino acid with a
biochemically different one
• e,g sickle cell anemia
• GAG (glutamic) GUC(valine)
28
 Nonsense mutation
substation of one base stops the
transcription
Ex. βo – thalassemia

substation of one base stops the transcription

29
 Silent mutation
• Point mutations which don’t have change
in the amino acids

UUU UUC

but both of the UUU&UUC codes for the

same amino acid[phenylalanine].

30
 B, Deletions and insertions

insertion or deletion of one or two base

pairs alters the reading frame of the
DNA strand resulting in Frameshift
mutations

If the number of base pairs involved in a

deletion is three or a multiple of three,
frameshift does not occur

31
 Deletion and insertion can result in one of the
following:
 Coding sequences => Frame shift changing
=> Non frame shift
changing

 None coding sequences- Promoter & enhancer

deletions
Frame shift mutations

33
 C,Trinucleotide repeat mutations
• Trinucleotide repeat mutations - these
mutations are characterized by
amplification of a sequence of three
nucleotides.
– E.g. in fragile X syndrome, there are 250
to 4000 tandem repeats of the sequence
CGG within a gene calledFMR1.
– In normal populations, the number of
repeats is small, averaging 29
34
 2.2. Mutation effect
• Mutation

• Abnormal protein/No protein/ Increased

protein

• Abnormal metabolic processes

• Tissue injury

• Genetic diseases.
Genetic Disorders
• Genetic disorders are far more common than is widely
appreciated.
• The lifetime frequency of genetic diseases is
estimated to be 670 per 1000.
• Furthermore, the genetic diseases encountered in
medical practice represent only the tip of the iceberg,
that is,
– those with less extreme genotypic errors that permit full
embryonic development and live birth.
– It is estimated that 50% of spontaneous abortuses during
the early months of gestation have a demonstrable
chromosomal abnormality
• About 1% of all newborn infants possess a gross
chromosomal abnormality,
 3. Categories of Genetic Diseases

• All Genetic diseases generally fall into one of

the following 4 categories:
A. Mendelian disorders.
B. Chromosomal disorders.
C. Multifactorial disorders.
D. Single gene diseases with non
classic patterns of inheritance.
A. SINGLE GENE (MENDELIAN) DISORDER

Gregor Mendel 1822-1884 Common edible peas

 A. Mendelian Disorders
Features:
• Caused by a single mutant gene.
• Affects transcription, mRNA processing, or
translation

• May affect any type of protein →Disease.

• Show the classic mendelian patterns of
inheritance.
• Are uncommon.
 Continued…
• Classification of mendelian disorders -
based on their patterns of inheritance.
1. Autosomal dominant inheritance.

2. Autosomal recessive inheritance.

3. X-linked recessive inheritance.
1. Autosomal dominant inheritance

a. The criteria
b. Additional features.

c. Pathogenesis
d. Clinical examples
 Continued…
a. Criteria
• The transmission of the trait is from
generation to generation without skipping.
• Except for new mutation, every affected child
will have an affected parent.
• both males and females are affected, and both
can transmit the condition
• Mating of affected heterozygote to a normal
homozygote, each child has a 50% chance to
inherit the abnormal allele & be affected & a 50
% chance inherit the normal allele.
 Continued…
• The 2 sexes are affected in equal numbers.
 Continued…
b. Additional features.
• New mutations
–With every autosomal dominant disorder, some proportion of
patients do not have affected parents
• Ex. Achondroplasia.
• Clinical features can be modified by variations in
penetrance and expressivity
• Reduced penetrance.
• This is referred to asincomplete penetrance.
• Penetrance is expressed in mathematical terms.
– Thus, 50% penetrance indicates that 50% of those who carry
the gene express the trait
• Variable expressivity- Phenotyic spectrum
• Ex. Neurofibromatosis type 1
• if a trait is seen in all individuals carrying the
mutant gene but is expressed differently
among individuals, the phenomenon is called
variable expressivity.
• For example, manifestations of
neurofibromatosis type 1 range from brownish
spots on the skin to multiple skin tumors and
skeletal deformities
• In many conditions the age at onset is delayed;
symptoms and signs may not appear until
adulthood (as in Huntington disease).
 Neurofibromatosis
• Café au lait spots
Neurofibromatosis
49
 Continued…
c. Pathogenesis
i. Loss of function- structural and regulator protein
- 50% reduction in these proteins.
- ex. LDL receptor and Collagen.

ii. Gain of function-

-much less common than loss of function
mutations.
-the mutant gene produces a toxic protein.
-ex. Huntington disease.
 Marfan syndrome

• A disorder of the connective tissues of the

body, manifested principally by changes in
the skeleton, eyes, and cardiovascular
system.
• Prevalence is estimated to be 1 in 5000
• 75% of cases are familial and show
autosomal dominant inheritance
• The remainder are sporadic and arise from
new mutations
 Continued…
Pathogenesis
• Defect in extra cellular glycoprotein fibrillin-1,
which forms a scaffolding for deposition of
elastin fibers.
• More than 500 distinct mutations in FBN1
gene are known, most resulting in an
abnormal protein.

• This abnormal protein disrupts assembly of

micro fibrils.
 Continued…
Clinical Signs
• Cardiovascular
o Dilatation and aneurysms of aorta
o Floppy mitral valve.

• Ocular
o Ectopia lentis
 Continued…
• Skeletal
o Pectus excavatum
o Scoliosis

o Joint laxity.
o Ratio of the upper segment to the lower
segment of body is usually 2 SDs below mean
for age, race, and sex
Continued…
Continued…
Joint
hypermobility

59
 Continued…
Diagnosis
• Clinical
 Skeletal changes
 Ectopia lentis
 Aortic aneurysm (ultrasound or x-ray)

• Histology
 Cystic medial necrosis of aorta (autopsy)
 Dissecting aortic aneurysm most common
cause of death
 Continued…
• Genetic and molecular
 Problematic because there are 500
distinct mutations.

 Detection of fibrillin defects in cultured

skin fibroblasts and DNA analysis of the
gene are now available from several
laboratories.
EHLERS-DANLOS SYNDROMES
• Hetrogenous group of disorders
characterized by defects in fibrillar
collagen synthesis or structure
• mode of inheritance encompasses all
three of the mendelian patterns
• important variants include
–Kyphoscoliosis type autosomal recessive
• mutations in the gene encoding lysyl hydroxylase
–Vascular type of EDS autosomal dominant
• abnormalities of type III collagen
–Classic type of EDS
• genes for type V collagen mutation (COL5A1 and
COL5A2 ) (only 30-50%)
– Arthrochalasia type and dermatosparaxis type
• defect in type I procollagen collagen
– Arthrochalasia COL1A1 &COL1A2 genes mutations
– Dermatosparaxis mutations in the procollagen-N-
peptidase genes (autosomal recessive)
Clinical features
• At least 10 clinical and genetic variants of
EDS are recognized
• Mostly involves tissues rich in collagen,
such as
– Skin hyperextensible
– Ligaments
– joints  hypermobile
                                                                            <>

66
67
Complications
• Joint dislocation
• Skin trauma
• serious internal complications.
– rupture of the colon and large arteries (vascular
EDS)
– ocular fragility with rupture of cornea and
retinal detachment (kyphoscoliosis EDS)
– diaphragmatic hernia (classic EDS
• Poor wound healing
 Familial hypercholesterolemia

• Most common autosomal dominant disorder

• Mutations in the gene for LDL receptor → No

functional LDL receptor → Leads to:

i. Impaired plasma LDL clearance.

ii. Impaired IDL uptake by the liver.

iii. Increased scavenger receptor

• heterozygotes 1:500
• 2-3x elevation of cholesterol
• Tendinous xanthomas
• premature atherosclerosis (adult life)
• Homozygotes
– 5-6x elevations in cholesterol
– Extensive skin xanthomas,
– coronary, cerebral and peripheral vascular disease at
an early age
– may develop MI <20yrs of age
• results in a decreased transport of LDL cholesterol
into cells and conspicuoushypercholesterolemia
72
 2. Autosomal recessive inheritance
a. Criteria:
If the trait is rare, parents & relatives other
than siblings are usually normal.

Mating of 2 phenotypically normal

heterozygotes, the segregation frequency
with each pregnancy is 25% homozygous
normal, 50% heterozygous normal, & 25%
homozygous affected.
 Continued…

• All children of two affected parents are

affected.

• Both sexes are affected in equal numbers.

Continued…
 Continued…

b. Additional features
Less variable expressivity than autosomal
dominant.
Commonly show complete penetrance.

Show signs & symptoms early in life.

 Continued…
c. Pathogenesis
• Loss of function mutations which result in
decreased enzyme proteins.
• Homozygotes → No normal enzyme →
Disease.

• Heterozygotes →Equal amounts of normal &

defective enzymes → Cells with half the
normal amount of the enzyme function
normally →No disease.
 d. Clinical examples

Non enzyme protein

mutation Enzyme protein mutation
• Sickle cell anemia • Phenylketonuria
• Thalassemias • Galactosemia
• Congenital adrenal • Homocystinuria
hyperplasia • Lysosomal storage
• Cystic fibrosis diseases
• Wilson disease. • Alpha 1 antitrypsin
• Hemochromatosis deficiency
• Glycogen storage disease
 Lysosomal Storage Diseases

• Lysosomes contain acid hydrolases that

catabolize the breakdown of complex
molecules.

• Lysosomes may contain.

substances from cellular organelles
(autophagy).
bacteria and other exogenous material
(heterophagy)
 Continued…
• Lysosomal storage diseases result from the
lack of any protein essential for their
function.

Lack of lysosomal enzyme.

Dysfunctional enzyme.
Defective post-translational processing of
enzyme.
 Continued…
E.G : Gaucher disease
• Is the most common lysosomal storage disorder.
• Is a disorder of lipid metabolism caused by
mutations in the gene encoding
glucocerebrosidase.
• Deficiency of glucocerebrosidase→
Accumulation of glucocerebroside
mononuclear phagocyte system &
the central nervous system
 Continued…
• Type I (chronic non neuronopathic)
• Type II ( acute neuronopathic) &

• Type III (Juvenile).

 Continued…
clinically manifests by
• Splenomegaly → Hypersplenism → Pancytopenia.
• Hepatomegaly

• Generalized lymphadenopathy
• Pathologic fractures & bone pain due to erosion of
the bone.

• First appearance of sings & symptoms in adult life.

• Progressive disease which is compatible with long
life.
 Continued…
Diagnosis
• Morphology
Gaucher cell is characteristic
• Glucocerebrosidase assay
Diagnostic of homozygous disease
Heterozygote values overlap with normal
• Genetic
Presence of 150 alleles complicates genetic
diagnosis
 Sickle-Cell Anemia
(Sickle-Cell Disease)
• The most
common genetic
disorder among
black people
• About 1 in 500
African Americans
has sickle-cell
anemia.
• Carriers are said
to have sickle-cell
trait
 Sickle-Cell Anemia
• Caused by an abnormal
gene on chromosome 11
• The gene is for one of
the polypeptide chains in
hemoglobin, a protein
found in red blood cells
that is responsible for
transporting oxygen
through the bloodstream
 Sickle-Cell Anemia
• Sickle-cell anemia causes hemoglobin to clump
within red blood cells, which distorts their shape
from the normal biconcave disc to a sickle shape.
• People with sickle-cell trait have
some abnormal hemoglobin but
do not have the symptoms of
sickle-cell disease.
 Symptoms of Sickle-Cell Anemia

• Abnormal hemoglobin cannot

deliver oxygen as efficiently
to cells as in healthy
individuals
– Fatigue
– Dizziness
– Headaches
• Sickled red blood cells cannot move as easily through
capillaries as normal RBCs
• Chronic pain, especially in bones
• Reduced immune response to infections
• Strokes
 3. X-linked recessive inheretance

• All sex-linked disorders are X-linked.

• There is no Y-liked inheritance because Y-
linked mutations result in infertility.

• X-linked disorders can be either recessive

(almost all) or dominant (rare).
• No male-to-male (i.e. father-to-son)
transmission of the trait
Continued…
 b. Clinical examples

Diabetes insipidus
Lesch-Nyhan syndrome

Fragile X syndrome
Duchenne muscular dystrophy
Hemophilia A & B
 Continued…
• Chronic granulomatous disease of childhood

• Glucose-6-phosphate dehydrogenase (G6PD)

deficiency
• Agammaglobulinemia

• Wiskott -Aldrich syndrome

 B. Chromosomal(Cytogenetic) Disorder

• Occur much more frequently than is generally

appreciated.

• Found in 50% of early spontaneous abortuse

& in 0.5% of live born infants.
• Caused by abnormal structure & number of
chromosomes.
 Continued…
1. Karyotype.
2. Types of chromosomal abnormalities.
3. Autosomal Cytogenetic disorders.
4. Sex chromosome Cytogenetic disorders

.
 1. Karyotype.

• A photomicrograph of the chromosomes of

an individual arranged in the standard
classification (i.e. metaphase chromosomes
arranged in order of decreasing length).
• Chromosome can be identified based on its
banding pattern & length.
Continued…
Continued…
 Shorthand system of notations
• First the total number of chromosomes is given.
• Second the sex chromosome constitution is
given.
• Finally any abnormality is described.

E.g. 1. A normal female karyotype is 46,XX.

E.g. 2. A female with trisomy 21 is described as

47,XX,+21.
2. Types of chromosomal abnormalities.

• Chromosomal anomalies may be

– Numerical (increase or decrease in number ) or
– Structural (e.g translocations ).
• Can affect autosomal or sex chromosomes

• Rarely seen clinically compared to real

occurrence
 1. Numeric Abnormalities
The normal 46,xx or xy is called euploid
Can be :
a. Aneuploidy
 is addition or loss of 1 or rarely 2 chromosomes.
 E,g , 47,XX
b. Polyploidy
 is the addition of complete haploid sets of
chromosomes.
 2n,3n….where n is haploid sets of chromosome
 E.g 69,XXY
 Count…

Numerical anomalies Results from

 anaphase lag- one normal cell and one
monosomic cell.
 non disjunction- result in trisomic,
tetrasomic… cells.
Nondisjunction in meiosis
 II. Structural anomalies
 This are rearrangements of genetic material
within or between different chromosomes.
 Result from breakage of chromosomes
followed by loss or rearrangement of genetic
material.
 Are of the following types.
a. Deletion
b. Iso chromosome formation
c. Inversion.
d. Translocation.
 a. Deletion
Is loss of a portion of a chromosome.
Has the following subtypes.
i.Terminal deletions .
 arise from one break.
 E.g. 46,XX, del(18p14)
ii. Interstitial deletions
 Arise from 2 breaks, loss of the interstitial
acentric segment & fusion at the break sites.
iii.Ring chromosomes
 Arise from breaks on either side of the
centromere & fusion at the breakpoints on
the centric segment. E.x. 46,XX, r(15).
 b. Isochromosome formation
Results when one arm of a chromosome is
lost & the remaining arm is duplicated,
resulting in a chromosome consisting of 2
short arms only or 2 long arms only.

 The arm on one side of the centromere is a

mirror image of the other.
 c. Inversion

• Is reunion of a chromosome broken at 2

points, in which the internal segment is
reinserted in an inverted position.
• Inversion can be
– pericentric or
– para centric
 d. Translocation.

 Is an exchange of chromosomal
segments between 2 non-homologous
chromosomes.

i. Reciprocal (balanced translocation)

ii. Robertsonian translocation
1.Reciprocal (balanced translocation)
ii.Robertsonian translocation
 3. Autosomal Cytogenetic disorder

practical examples of chromosomal disorders :

Down syndrome- Chromosome 21

Edward syndrome- Chromosome 18

Patau syndrome- Chromosome 13

Chromosome 22q11 deletion syndrome
 Down Syndrome (Trisomy 21 )

• Most common chromosomal disorder

• Affects 1 in 750 newborns overall, but is
related to maternal age.
• Usually results from meiotic nondisjunciton of
chromosome 21
• 4% result from Robertsonian translocation of
chromosome 21 to another chromosome.
• 1% result from mitotic nondisjunction of
chromosome 21 during early embryogenesis:
mosaics
Continued…
Clinical Features of Down Syndrome
Trisomy 21 (Down)
Prenatal Diagnosis
• Amniocentesis
Most common modality
Performed at 15-17 weeks gestation

• Chorionic Villus Sampling (CVS)

Second most common
Performed at 10-12 weeks gestation

• Percutaneous umbilical blood sampling (PUBS)

Performed in second and third trimesters
Usually prompted by ultrasound abnormalities of
fetus
 4. Sex chromosome Cytogenetic
disorders
Imbalances of X-chromosomes are better
tolerated than those of autosomes.
Lyonization – Murray Lyon
 During 16th day of embryonic life one X-
chromosome in females is randomly
inactivated
 Inactivation persists in all subsequent cells.

• Increased number of X-chromosomes in either

males or females lead to mental retardation
(Murray) Barr body
 Klinefelter Syndrome(47,XXY)
• A male hypogonadism that occurs when there
are two or more X-chromosomes and one or
more Y-chromosomes
• Incidence is 1 in 500 male births
• Usually (82% of cases) 47,XXY
 maternal (60%) or paternal (40%)
nondisjunction during meiotic divisions
• 15% are mosaics, usually 46,XY/47,XXY
Clinical Features
• Testicular abnormality does not develop before
puberty.
 Seminiferous tubules are atrophic resulting in
reduced spermatogenesis, infertility, small firm
testes, and increased FSH
 Testosterone levels are reduced
-impotence and increased LH
-lack of secondary male sexual
characteristics
• Mental retardation is unusual but IQ may be
below normal
• Mosaics are less severely affected
 Turner syndrome(45,X0)
• This is loss of one of the sex chromosome
• Genetically and phenotipicaly females but
are infertile
• Secondary sexual characters are not well
developed
• Could be due to monogenic or
chromosomal
.
Turner syndrome
SEX DETERMINATION
Criteria include
– Genetic sex (chromosomal sex) presence or absence of
y chromosome
– Gonadal sex determined by the histology of the gonads
– Ductal sex  determined by whether the muellerian or
wolffian ducts developed
– Phenotypic sex ("genital sex") is determined by the external
genitalia
Sexual ambiguity
• disagreement among the various criteria for
determining sex

138
• True hermaphrodites
– have both ovarian and testicular tissue
– Extremely rare
– in some cases ,there is a testes on one side
and an ovary on the other
– In others there is a combined ovarian and
testicular tissue – ovotestes
– 46, XX in 50%, the remaining are mosaics with
46,XX/46XY

139
True hermaphrodite
• Pseudohermaphrodites
– have disparity between gonadal and phenotypic sex
• Female pseudohermaphrodite
– has ovaries and penis, usually because of exposure
to male hormones before birth
– 46XX, 20 to androgen in congenital adrenal
hyperplasia
– The usual problem is a glitch in glucocorticoid
synthesis, in which steroids are shunted into male
pathways
– The "penis" is really a big clitoris

141
male pseudohermaphrodite
• has a vulva and testes
• defects in androgen
– synthesis
– action (receptor)
– Both
• Eg.testicular feminization

142
 C. Multifactorial Disorder
• Are more common than mendelian disorders.
• Result from the combined actions of
environmental factors & 2 or more mutant genes
having additive effects (i.e. the greater the
number of inherited mutant genes, the more
severe the phenotypic expression of the disease).
• The disease clinically manifests only when
– the combined influences of the genes &
– the environment cross a certain threshold.
• 2-7% recurrence for 10 relatives
 Continued…
• Diabetes mellitus
• Hypertension
• Ischemic heart disease
• Gout
• Schizophrenia
 Continued…
• Bipolar disorders
• Neural tube defects

• Cleft lip/ cleft palate

• Pyloric stenosis

• Congenital heart disease, etc….

 Features:

1. The risk of expressing a multifactorial

disorder partly depends on the number of
inherited
mutant genes.

2. The risk of recurrence of the disorder is the

same for all first degree relatives of the
affected individual & this is in the range of
2-7%.
 Continued…
3. The concordance rate for identical twins is 20
– 40%.
4. When one child is affected, the chance that
the
next child will be affected is 7%.

5. When 2 children are affected, then the chance

that the next child will be affected increases to
9%.
 D. Single gene diseases with non classic
patterns of inheritance.

A. Diseases caused by mutations in

mitochondrial genes.
E.g. Leber hereditary optic neuropathy

B. Diseases associated with genomic imprinting

E.g Angelman syndrome
C. Disorders caused by triplet repeat mutations
E.g. Fragile X syndrome
4. Diagnostic Approach
Continued…
Continued…
Continued…
Polymerase Chain Reaction
 DNA Microarray
Examine how active thousands of genes are at any given
time.
Continued…
 5. Genetic Counseling
• Definition
• Principles of Genetic Counseling
i. Diagnosis
ii. Education
iii. Supportive counseling
iv. Follow-up
Definition
• A communication process between a healthcare
professional trained in genetics and an individual or
family affected by or at risk for an inherited disorder.
Principles of Genetic Counseling
• To provide appropriate information for families
• Genetic counselors follow several guiding principles.
• Include providing an
– accurate diagnosis,
– education of family members,
– supportive counseling, and
– follow-up.
 Continued…
I. Diagnosis
• The single most important aspect of genetic
evaluation.
• Wrong information result in further harm
• The genetics team may order diagnostic
testing for a suspected condition.
• Counselors inform families of the benefits,
risks and limitations of such testing before
testing begins.
 Continued…
ii. Education
The known and unknown aspects of a
particular disorder.
Its natural history
Prognosis for affected individuals.

Existing treatment and/or management options.

Recurrence risk
 Continued…
iii. Supportive counselling
• Depending on the seriousness of the disease,
parents may feel
 Guilt or shame
 Grief and anger
 Depression
 Continued…
iv. Follow up
Summary of the important medical and
genetic information in a letter to the family so
that it can be accessed at any time.

Further counseling if questions arise or

emotional issues become overwhelming.
For referral preparation
THANK YOU!