Chapter 8 The Nursing Role

in Genetic Assessment and

Counselling
Gene Replacement Therapy and Gene Editing

• Gene Replacement Therapy- is an experimental technique

that uses genes to treat or prevent disease.

• Gene Editing- DNA is inserted, deleted, modified or replaced in

the genome of a living organism targets the insertions to site specific
locations.
GENETIC DISORDERS
• may occur at the moment an ovum and a sperm
fuse or even earlier, in the meiotic division phase
of the gametes
 50% of 1st trimester spontaneous miscarriages
GENETIC DISORDERS
 Or Inherited disorders = are disorders that can
be passed from one generation to the next
because they result from some disorder in the
gene or chromosome structure.
 Genetics = is the study of the way such
disorders occur.
 Cytogenetics = is the study of chromosomes by
light microscopy and the method by which
chromosomal aberrations are identified.
NATURE OF INHERITANCE
 Genes = are the basic units of heredity that
determine both physical and cognitive
characteristics of people.
 Are composed of segments of DNA, which are woven
into strands in the nucleus of all body cells to form
chromosome.
CHROMOSOMES
CHROMOSOME
NATURE OF INHERITANCE
 Alleles = are the two like genes on autosomes.
 Phenotype = refers to a person’s outward
appearance or the expression of genes.
 Genotype = refers to a person’s actual gene
composition.
 Genome = is the complete set of genes present
(about 50,000 to 100,000).
 GENETIC INFORMATION
• Gene – basic unit of genetic
information. Genes determine the
inherited characters.
• Genome – the collection of genetic
information.
• Chromosomes – storage units of
genes.
• DNA - is a nucleic acid that contains
the genetic instructions specifying
the biological development of all
cellular forms of life

9
MENDELIAN INHERITANCE
 Gregor Mendel = described the principle of
generic inheritance.
 When dominant gene is paired with nondominant
(recessive) ones, the dominant genes are always
expressed in preference to the recessive genes.
 Ex: a gene for brown eyes is dominant over one for
blue eyes.
 2 healthy genes-HOMOZYGOUS
 2 unhealthy genes-HETEROZYGOUS
MEDICAL GENETICS
When studying rare disorders, general
patterns of inheritance are observed:

• Autosomal recessive
• Autosomal dominant
• X-linked recessive
• X-linked dominant

11
HOW DOES IT WORK?
 DOMINANT VS. RECESSIVE

A dominant allele is
expressed even if it is
paired with a recessive
allele.

A recessive allele is only

visible when paired with
another recessive allele.

15
INHERITANCE OF DISEASE

Autosomal Dominant
•either a person has 2 unhealthy
genes(HOMOZYGOUS DOMINANT)
•e.g.DD or is heterozygous, with the gene causing
the disease stronger than the corresponding
healthy recessive gene for the same trait e.g. Dd
AUTOSOMAL DOMINANT
DISORDERS

 Huntington disease-progressive neuro do,

 Marfan syndrome(CT tissue disorder),

 breast & ovarian CA,

 osteogenesis imperfecta(bones are brittle)

Autosomal dominant
 Affected males and
females appear in each
generation of the
pedigree.
 Affected mothers and
fathers transmit the
phenotype to both sons
and daughters.
 e.g., Huntington disease.

18
AUTOSOMAL RECESSIVE
 The disease appears in
M and F children of
unaffected parents.
 e.g., cystic fibrosis

19
Autosomal Recessive cont’d
•disease does not occur unless 2 genes for the
disease are present(homozygous recessive pattern)

-CF, albinism, adrenogenital syndrome, Tay-Sach’s,

galactosemia, PKU, Rh-incompatibility
X-linked Dominant Inheritance
• genes are located on,and transmitted only by the
female sex chromosome(X chromosome)
• if the affected gene is dominant, only 1 X
chromosome with the trait need be present for
symptoms of the disorder to be manifested

• -Alport’s syndrome- progressive kidney failure

disorder
X-linked Recessive
Inheritance
 Usually, only males will have the disorder

 history
of girls dying at birth for unknown
reasons(females with affected gene on both X
chromosomes)

 hemophilia A, Christmas disease, color

blindness, Duchenne muscular dystrophy and
fragile X syndrome(cognitive challenge
syndrome)
Multifactorial (Polygenic)
Inheritance
 from multiple gene combinations + environmental
factors
 heart ds, DM, cleft palate, NTDs, pyloric stenosis
CHROMOSOMAL
ABNORMALITIES(CYTOGENIC
DISORDERS)
Abnormalities at fault in the
number/structure of chromosome
which results in missing or
distorted genes
 When chromosomes are photographed and displayed,
the resulting arrangement is termed a KARYOTYPE
 fluorescent in situ hybridization (FISH)-the
number of chromosomes and specific parts of
chromosomes can be id by karyotyping or by this
process
 Nondisjunction
Abnormalities

 the division is uneven(NONDISJUNCTION) resulting

to 1 sperm/ovum having 24 & the other 22
 -if this fuses with a normal sperm/ovum, the zygote
will have 47 or 45 chromosomes
 Down’s syndrome(Trisomy 21) increases with maternal
& paternal age
 Turner & Klinefelter syndrome
NON-DISJUNCTION
Deletion Abnormalities
 chromosome disorder in which part of the
chromosome breaks during cell division,
causing the affected person to have the normal #
of chromosomes +/- an extra portion of a
chromosome,
e.g 45.75 or 47.5

 Cri-Du-Chat syndrome(46XY5q-)Cat Cry Syndrome,

1 portion of chr. 5 is missing
DELETION
 Translocation Abnormalities

• a child gains an additional chromosome through

another route
• TRISOMY 21
TRANSLOCATION ABNORMALITIES
TRANSLOCATION ABNORMALITIES
Mosaicism
• when the nondisjunction
disorder occurs after
fertilization of the ovum, as the
structure begins mitotic cell division

• different cells in the body will

have different chromosome
counts
MOSAICISM
Isochromosomes
chr accidentally divides not by a
vertical separation but by a
horizontal one, a new
chromosome with mismatched
long and short arms can result.
much the same effect as a
translocation
Turner’s syndrome
ISOCHROMOSOMES
GENETIC COUNSELING
Purposes:
 Provide concrete, accurate information:
process of inheritance & inherited
disorders
 Allow people to make informed choices
about future reproduction
 Offer support to people who are affected
by genetic disorders
Couples who may benefit include
those:
 who have a child with congenital disorder or an
inborn error of metabolism
 whose close relatives have a child with a genetic
disorder such as translocation disorder or inborn
error of metabolism
 Who are known balanced translocation carriers
 With inborn error of metabolism or chromosomal
disorder
 Who are a consanguineous couple(closely related)
 With the woman older than 35 and the man older
than 55
 Are of ethnic backgrounds in which specific
illnesses are known to occur; Chinese(G6PD,
Mediterranean, thalassemia)
NURSING RESPONSIBILITIES
 Explaining to a couple what procedures
they can expect to undergo
 Explaining how different genetic
screening tests are done and when they
are usually offered
 Supporting a couple during their wait for
test results
 Assisting couples in values clarification,
planning, and decision-making based on
the results
 *do not impose your own values or
opinions
ASSESSMENT FOR GENETIC
DISORDERS

 HISTORY
 Document diseases in family members

 Ethnic background

 Mother’s age, spontaneous miscarriage

PHYSICAL ASSESSMENT
 PE of family member with a disorder,
siblings and the couple
 Check:space between the eyes, height,
contour, shape of ears, number of fingers &
toes, webbing, dermatoglyphics(markings
on skin), abnormal fingerprints, palmar
creases, abnormal hair whorls or hair
coloring
DIAGNOSTIC TESTING

 Karyotyping-sample of peripheral venous blood or

scraping of cells from buccal cavity; cells are grown to
metaphase, stained, placed under a microscope &
photographed( chr are id according to size, shape &
stain)
 *Newer method of staining, FISH, can be done
immediately rather than waiting for metaphase;
WHAT FISH TESTING IS
FISH stands for fluorescence in
situ hybridisation.
 looks for gene changes in cells.
 FISH tests look for specific genes or
parts of genes.
Maternal Serum Screening- AFP by the fetal liver
that peaks in maternal serum between the 13th and
32nd week;
-a group of tests used in the second trimester of
pregnancy to help evaluate a woman's risk of carrying
a baby with chromosome disorders, including Down
syndrome (trisomy 21) or Edwards syndrome (trisomy
18), or neural tube defects such as spina bifida or a
condition called anencephaly.

level is elevated with fetal spinal cord disease

 decreased with fetal chromosomal disorder like
Trisomy 21
Chorionic Villi Sampling(CVS)-
involves retrieval & analysis of
chorionic villi from the growing
placenta for chromosome or DNA
analysis
Amniocentesis- withdrawal of AF
through the abdominal wall for
analysis at the 14th to 16th week
Percutaneous Umbilical Blood
Sampling(PUBS)- or cordocentesis
is the removal of fetal cord blood at
17 weeks using amniocentesis
methods
COMMON CHROMOSOMAL DISORDERS
TRISOMY 13 SYNDROME (47XY13+ OR 47XX13+) OR
PATAU SYNDROME

extra chr 13, severely cognitively

challenged
midline body disorders like cleft
lip/palate, heart defects, abn
genitalia, microcephaly,
microphthalmia, low-set ears;
most do not survive beyond early
childhood
TRISOMY 13
Trisomy 18 (47XX18+ or
47XY18+)/Edward’s
Syndrome
they have 3 copies of chr 18
severely cognitively challenged,
SGA, low-set ears, smalljaw,
congenital heart defects, misshapen
fingers & toes, rocker-bottom feet
do not survive beyond early infancy
TRISOMY 18
Cri-du-chat syndrome (46XX5p- or 45XY5p-)

 result of missing portion of chromosome 5

 abnormal cry, small head, wide-set eyes, downward
slant to the palpebral fissure, severely cognitively
challenged
CRI-DU-CHAT
 Turner Syndrome (45XO) or Gonadal dysgenesis
 only 1 functional X chromosome
 short in stature
 streak(small non-functional) ovaries, sterile, & secondary
sex characteristics except for pubic hair, do not develop
during puberty
 hairline at the nape of the neck is low-set
 neck is webbed & short,
 NB may have edema of the hands & feet & anomalies like
CoA & kidney disorders
 learning disabilities
 human growth hormone and estrogen may cause
appearance of sex characteristics
TURNER SYNDROME
Klinefelter Syndrome (47XXY)

 males with extra X chromosome

 puberty, no development of secondary sex
characteristics; small testes with ineffective
sperm, gynecomastia, increased risk for
breast CA
KLINEFELTER SYNDROME
Fragile X Syndrome (46XY23q-)

• most common cause of cognitive challenge in males

• Xlinked -1 long arm of X chr is defective
• before puberty, boys demonstrate maladaptive behaviours
like hyperactivity or autism, reduced intellectual
functioning with marked deficits in speech & arithmetic
• Broad forehead, long face with high forehead, prominent
lower jaw, large, protruding ears, hyperextensive joints,
cardiac disorders
• after puberty, large testicles;
• fertile
FRAGILE X SYNDROME
DOWN SYNDROME-TRISOMY 21
Down Syndrome (Trisomy 21) (47XY21+ or 47XX21+)

• most frequently occurring

chromosomal abnormality (1 in 800
pregnancies)
TRISOMY 21 SYMPTOMS
• broad & flat nose,
• eyelids have an extra fold of tissue at the inner
canthus(epicanthal fold)
• palpebral fissure tends to slant upward,
• iris may have white specks(Brushfield spots)
• tongue may protrude since the oral cavity is
small,
• back of the head is flat,
 poor muscle tone(rag-doll appearance) that the toe can
touch the nose,
 fingers are short & thick and the little finger is curved
inward,
 wide space between the 1 st & 2nd toes & between the 1st
& 2nd fingers, palm of hand has a simian line
 cognitively-challenged to some degree(50-70%)

 neck is short, extra pad of fat at the base of the head

causes the skin to be loose it can be lifted
easily(puppy’s neck),
Childhood Tumors
Retinoblastoma
Wilm’s tumor
 Neuroblastoma
RETINOBLASTOMA
 a rare form of cancer that rapidly develops from
the immature cells of a retina, the light-detecting
tissue of the eye. It is the most common primary
malignant intraocular cancer in children, and it
is almost exclusively found in young children.
WILM’S TUMOR
 a rare kidney cancer that primarily affects
children. Also known as NEPHROBLASTOMA,
it's the most common cancer of the kidneys in
children. Wilms' tumor most often affects
children ages 3 to 4 and becomes much less
common after age 5.
NEUROBLASTOMA
 a cancer that develops from immature nerve cells
found in several areas of the body.

 most commonly arises in and around the adrenal

glands, which have similar origins to nerve cells
and sit atop the kidneys.