Genetics
Denice Gardner, MSN, NNP-BC
Objectives
 Discuss genetics and its affects on the
newborn
Genetics
• Pictures included in presentation were
obtained from the Mosby’s Nursing
Consult web site
• Graphics used in presentation were
created by the author
Terminology
 Genetics- study of heredity
 Chromosome- structural element in a cell
that contains the genes and all the genetic
information; human cells have 23 pairs of
chromosomes
 DNA- double-stranded nucleotide that
carries genetic material
 Gene- segments of the DNA that are
responsible for inherited traits; contain the
“blueprint for everything that will make “you”
Terminology
 Allele- variations in a gene; segregates
during meiosis; receive only one pair
from each parent; only 2 alleles can be
present in one person
 Autosome- one of the 22 chromosomes
that do NOT determine the sex of a
person
 Sex chromosome- the X & Y
chromosome that determines the sex of a
person
Terminology
 Gamete- one of the 2 cells that joins
together during sexual reproduction to
create a new being
 Genotype- genetic make-up of a person
 Phenotype- biochemical, physiologic, &
morphologic characteristics of a person
(hair color, skin type, etc.) & is
determined by his/her genotype and
environment
Terminology
 Haploid- number of chromosomes in a
gamete; half the number of chromosomes in
a person, 23 chromosomes
 Diploid- contains a set of maternal &
paternal chromosomes to equal 46 total
chromosomes
 Locus- location of the gene in the
chromosome
 Penetrance- degree to which an inherited
trait will be expressed in a person
Dominant & Recessive Genes
 Dominant- expressed & transmitted even if
only ONE parent has the gene
 Recessive- expressed only when BOTH
parents have the gene
 Homozygous- two identical alleles for a
particular gene (one from each parent)
 Heterozygous- two different alleles for a
particular gene
Possible Combinations
 Both can be dominant (AA)
 Both can be recessive (aa)
 One can be dominant & one can be
recessive (Aa)
Autosomal Dominant
 Appears in every generation without
skipping
 Either parent can pass the gene on to their
children
 Risk for affected individuals to have affected
children is 50% with every pregnancy
 If 2 affected parents mate, 75% of their
children will be affected
 Unaffected individuals do NOT have
affected children
 Trait is found equally in males and females
Autosomal Dominant
Affected
(Aa)
Normal
(aa)
Normal
(aa)
Affected
(Aa)
Affected
(Aa)
Normal
(aa)
Autosomal Recessive
 Expressed only when both parents transmits
it to their offspring
 Alternates generations
 If 2 affected people mate, all children with
be affected
 If 2 carriers mate, the risk of having an
affected offspring is 25%
 If a carrier & an affected person mate, the
risk of having an affected offspring is 50%
 Risk of an unaffected carrier having a child
who is a carrier is 50% with each pregnancy
Autosomal Recessive
Carrier
(Aa)
Normal
(AA)
Heterozygous
(Aa)
Heterozygous
(Aa)
Carrier
(Aa)
Affected
(aa)
X-Linked Dominant
 Female children of affected males are ALL
affected
 Male children of affected males are
unaffected
 Trait appears in every generation
 All children of affected females MAY be
affected
 X-Linked dominant problems affect twice as
many females as males
X-Linked Dominant
Normal
Son (XY)
Affected
Daughter
(XX)
Normal
Mom (XX)
Affected
Dad (XY)
Normal
Son (XY)
Affected
Daughter
(XX)
Normal
Daughter
(XX)
Affected
Son (XY)
Affected
Mom (XX)
Normal
Dad (XY)
Affected
Daughter
(XX)
Normal
Son (XY)
X-Linked Recessive
 Only Male children are affected. (Female
may be affected if mother is a carrier and
father is affected)
 Traits cannot be transmitted from father
to son because the father only
contributes the Y chromosome
 Transmission of the trait occurs from
father to all daughters (who will be
carriers)
X-Linked Recessive
 Heterozygous females transmit the gene
to half of their sons, who will be affected,
& to half their daughters, who will be
carriers
 Transmission is horizontal among males
of the same generation & then skips a
generation
 Carrier females transmit the disorder
X-Linked Recessive
Normal
Son
(XY)
Carrier
Daughter
(XX)
Normal
Mom (XX)
Affected
Dad (XY)
Normal
Son (XY)
Carrier
Daughter
(XX)
Carrier
Daughter
(XY)
Normal
Son
(XY)
Carrier
Mom
(XY)
Normal
Dad (XY)
Affected
Son (XY)
Normal
Daughter
(XX)
Chromosomal Defects: Abnormal Number
 Polyploidy- contains more than 2 sets of
chromosomes, showing multiples of the
haploid number; usually dies as embryos
or fetuses
 Nonmultiples- designated by the suffix
“-somy”
Monosomy- one less than the diploid
number (45 chromosomes)
Trisomy- one more than the haploid
number (47 chromosomes)
Chromosome Defects: Abnormal Number
 CausesNondisjunction- failure of paired
chromosomes to separate during cell
division; most common cause of all
chromosome disorders
Chromosome lag- failure of a chromosome
to travel to the correct daughter cell
Anaphase lag- failure of a chromosome or
chromatin to be incorporated into one of the
daughter nuclei following cell division as a
result of delayed movement during
anaphase
:
Chromosomal Defects: Abnormal
Number
Mosaicism:
Nondisjunction of an anaphase lag
that occurs during cell division after
fertilization
Cells within the same person that
have different genetic make-up
Chromosomal Defects: Abnormal
Structure
 Deletion- loss of part of a chromosome
 Translocations- displacement of part of a
chromosome to an abnormal site, whether
on another chromosome or in the wrong
position on the same chromosome
 Polygenic effects- type of inheritance in
which a trait is dependent on many different
gene pairs with cumulative effects
Chromosome Defects: Abnormal
Structure
 Environmental influences- nutrition, drugs, &
living environment (radiation, pollution,
bacteria, virus) that affect the genetic makeup & developing embryo while in utero
 Duplication- duplication of an area of the
DNA that contain contains a gene; results in
mutations that have no deleterious affects
on a person
Chromosomal Defects: Abnormal
Structure
 Inversion- area of a chromosome breaks off
and then reattaches itself in the opposite
direction
 Nonreciprocal translocation- one-way
transfer of genes from one chromosome to
another
Chromosomal Defects: Abnormal
Structure
 Basic Generalizations
Loss of an entire chromosome is
usually incompatible with life
One X chromosome is necessary for
life & development
If the Y-chromosome is missing, life &
development may continue but will
follow female pathways
Chromosomal Defects: Abnormal
Structure
Extra entire chromosomes,
translocations of extra chromatin
material, & insertion of extra chromatin
material are often compatible with life
& development
Multiple congenital structural defects
are present when gross aberrations
are present
Prenatal Testing
 Alpha-Fetoprotein Test (AFP)
Usually done at 16-18 weeks gestation
Is a screening test, not a diagnostic
test
If abnormal, ultrasound should be
obtained
Prenatal Testing
Elevated AFP may indicate
Greater gestational age than expected
Multiple gestation
Risk of neonatal complications,
including spontaneous abortion, PTL,
or IUGR
Fetal structural defects: neural tube,
abdominal wall, esophageal or
intestinal obstruction, or renal
anomalies
Prenatal Testing
 Multiple Marker Screen (“Quad Screen”)
Measures AFP, hCG, unconjugated
estriol (uE3), & dimeric inhibin-A (DIA)
Useful in detecting conditions like
trisomies
Usually done between 15-20 weeks
gestation
If, abnormal, ultrasound should be
obtained
Prenatal Testing
 Ultrasonography- uses high-frequency
sound waves to display sectional planes of
the uterine contents on a monitor
Recommended by 16-20 weeks of age
for gestational age verification &
assessment
Used to detect abnormalities of the
fetus, placenta, amniotic fluid, & uterus
& to monitor changes in anatomy &
growth with serial ultrasounds
Only as good as the person’s trainingnot just on the equipment
Prenatal Testing
 Amniocentesis- removal of amniotic fluid
through a needle placed through the
abdomen, usually in conjunction with
ultrasonography, for the purpose of
chromosome analysis & other biochemical
tests
Usually done between 16-18 weeks
gestation
Indications for procedure:
Advanced maternal age (>35yrs at
time of delivery)
Previous fetus with a neural tube
Prenatal Testing
More indications for procedure
Both parents known heterozygous
carriers of autosomal recessive
chromosome
Both parents known carriers of sexlinked recessive disorder
Patient or partner with balanced
chromosomal translocation of his or
her chromosomes
High or low AFP with accurate
gestational age
Previous fetus with Down’s Syndrome
Prenatal Testing
 Chorionic Villi Sampling- insertion of a
needle through either the cervical os or
through the abdomen, in conjunction with
ultrasound, to obtain a sample of fetal tissue
from the growing placenta for chromosomal
analysis & other biochemical tests
Usually done at 8-10 weeks
Indications:
Patient prefers to make decision
regarding pregnancy in the 1st trimester
Severe oligohydramnios
Prenatal Testing
Complications:
Multiple gestation
Uterine bleeding during this pregnancy
Active genital herpes or other cervical
infection
Uterine fibroids
Takes 24-48 hours for initial results
Prenatal Testing
 Percutaneous Umbilical Cord Samplingremoval of blood through a needle inserted
through the abdomen and into the umbilical
vein, in conjunction with ultrasound
Performed from 18 weeks until term
Indications:
Patient wants fast results to support
decision regarding pregnancy
Abnormality is identified late in
pregnancy
Prenatal Testing
More indications:
Patient has been exposed to infectious
disease that could affect development
of fetus
Blood incompatibility (Rh disease)
Drug or chemical level is fetal blood
needs to be assessed
Fetal blood analysis 3 days
Postnatal Testing
 Chromosome analysis/karyotypephotograph of the chromosomal make-up of
an individual, including the number of
chromosomes & any abnormalities
 Polymerase Chain Reaction (PCR)technique to copy small segments of DNA
for analysis; useful in disorders with
recurring mutations
 High-resolution banding/prometaphase
banding- useful for identification of subtle
chromosomes
Postnatal Testing
 Microarray- assesses the ability of mRNA
molecules to and interact with DNA
molecules; assesses gene expression within
a single sample or in comparison to 2
different cell types or tissue samples; need
only a small sample of blood or tissue; can
be done on healthy or diseased tissue
Postnatal Testing
 Fluorescence in situ hybridization (FISH)cytogenic technique that can be used to
detect and localize the presence or absence
of specific DNA sequences on
chromosomes; uses fluorescent probes that
bind to only those parts of the chromosome
with which they show a high degree of
sequence similarity
Genetic Counseling
 Goal- to assist the family in understanding
Diagnosis
Role of heredity
Recurrence risks & options
Possible courses of actions
Methods of ongoing adjustment
Genetic Counseling
 Indications
Previously affected child, parent, or
grandparent
Congenital malformation
Sensory defect
Metabolic disorder
Mental retardation
Known or suspected chromosome
abnormality
Neuromuscular disorder
Degenerative CNS disease
Genetic Counseling
 More indications
Previously affected cousins
Muscular dystrophy
Hemophilia
Hydrocephalus
Consanguinity
Hazards of ionizing radiation
Recurrent miscarriages
Concern for teratogenic effect
Advanced maternal age
High or low AFP
Newborn Care: Terminology
 Birth defect- structural or functional
abnormality of the body that is present from
birth
 Syndrome- group of anomalies that cannot
otherwise be explained & occurs in similar
patterns of expressions (ex. Fetal alcohol
syndrome)
 Sequence- primary anomaly that sets a
pattern for other anomalies (Ex. Pierre
Robin)
Newborn Care: Terminology
 Association- nonrandom occurrence of
multiple anomalies in 2 or more people (ex.
CHARGE)
 Malformation- abnormality of
morphogenesis due to intrinsic problems
within the developing structures (ex. Neural
tube defect)
 Deformation- abnormality of morphogenesis
due to intrinsic problems within the
developing structures (ex. uterine position
defects)
Newborn Care: Terminology
 Disruption- abnormality of morphogenesis
due to disruptive forces or pressure acting
on the developing structures (ex. Amniotic
bands)
 Genetic heterogeneity- different causes may
produce different characteristics (ex.
Hydrocephalus, cleft lip & palate)
Newborn Care
 History
Family
History of 3 generations
Defects in the family history related to
the problem with the child
History of consanguinity
Reproductive history (frequent
miscarriages???)
Pattern of inheritance of the problem
Newborn Care
Prenatal
Length of gestation
Fetal activity level
Maternal exposure: infection, illness,
high fever, meds, alcohol, smoking, Xrays, known teratogens, illicit or
prescription drug use
Obstetric factors: uterine
malformations, labor complications,
presenting fetal part
Neonatal factors: birth weight, length,
HC, Apgar score
Newborn Care: Assessment
 Physical Exam
General: asymmetry, inappropriate size &
length
Face: configuration; centered features
with normal spacing; round, triangular,
birdlike, elfin, or expressionless
characteristics
Head: size of anterior fontanelle,
prominence of frontal bone, flattened or
prominent occiput, abnormalities in shape
(large or small)
Newborn Care: Assessment
Skin: intact, presence of skin tags, open
sinuses, tracts, etc.
Hair: texture, presence of whorls
Eyes: structure, color of iris, presence of
colobomas, centering & spacing of
epicanthal folds, ptosis, slanting, eyelash
length
Ears: protruding or prominent shape,
location, low set, unilateral or bilateral
defect, presence &/or degree of rotation
Newborn Care: Assessment
 Nose: beaked, bulbous, pinched, upturned,
misshapen, two nares, flattened bridge,
patency, centered on face
 Oral: intact palate, presence of smooth
philtrum, natal teeth, shape & size of
tongue, mouth & jaw
 Neck: short &/or webbed, redundant folds
 Chest: symmetric, presence of accessory
nipples, spacing of nipples, shape of chest
Newborn Care: Assessment
 Abdomen: number of cord vessels,
presence of bowel sounds; shape, presence
or abd wall defects & abd wall musculature,
prune belly
 GU(male): hypospadius, chordee,
ambiguous genitalia, descended testis
 Anus: patency, presence, position
Newborn Care
 Provide grief counseling
 Encourage genetic counseling
 Facilitate family use of available support
systems
 Provide emotional support
Newborn Care
 Identify normal aspects of neonate that can
coexist with neonate
 Encourage parent participation in infant’s
care
 Discuss treatment options, including risks &
benefits
 Provide educational information
 Identify primary abnormality
 Recognize defects that may have more than
one cause
Newborn Care
 Determine category of malformation,
according to etiology
Malformation
Deformation
Disruption
Syndrome
Association
Sequence
Genetic heterogeneity
VATER Association
 Vertebral anomalies, Anal atresia,
Tracheoesophageal fistula, Radial & renal
dyspalsia
Etiology/precipitating factors: unknown
Clinical presentation
Vertebral anomalies
Anal atresia, with or without fistula
Radial dysplasia, including thumb or
radial hypoplasia, polydactyly, &
syndactyly
Renal anomaly
Single umbilical artery
VATER Association
Complications
Failure to thrive
Possibility of normal life after slow
mental development during infancy
Care
Supportive: prognosis & management
depend on extent & severity of
anomaly
Surgery: surgical correction of
anomalies
VACTERL Association
 Vertebral abnormalities, Anal atresia,
Cardiac abnormalities, Tracheoesophageal
fistula &/or esophageal atresia, Renal
agenesis or dysplasia, & Limb defects
 Etiology/precipitating factors:
Unknown
Injury between 4-6 weeks to a specific
mesodermal area may produce
overstimulation of the hindgut, lower
vertebral column, & developing kidney
Average of 7-8 abnormalities per patient
VACTERL Association
 Clinical Presentation
Vertebral anomalies
Anal atresia with or without fistula
Cardiac anomalies; commonly VSDs
TEF with or without esophageal atresia
Radial Dysplasia, including thumb or
radial hypoplasia, polydactyly, &
syndactyly
Renal anomaly
Single umbilical artery
VACTERL Association
 Complications
Failure to thrive
Normal life: minimal CNS anomalies with
only occasional mental retardation
 Care:
Supportive: prognosis & management
depend on extent & severity of anomaly
Surgery: surgical correction of anomalies
Trisomy 13
 Etiology
Maternal age felt to be a factor
47 chromosomes (3 of chromosome 13)
20% of defects are caused by
translocations, some are familial
5% occur as a result of mosaicism
Trisomy 13
 Presentation
Growth deficiency
Head: microcephaly with sloping
forehead, midline scalp defects
Eyes: abnormally close eyes,
microphthalmia, colobomas, glaucoma
Ears: low-set & malformed, atresia of
auditory canals
Nose: prominent nasal bridge
Mouth: bilateral cleft lip &/or palate
Neck: short neck with excessive skin
Trisomy 13
 Presentation
 Musculoskeletal
Polydactyly
Overlapping of fingers with single palmar
crease
Narrow, hyperconvex fingernails
Flexion deformities of arms & wrists
Prominent heel resulting in rocker-bottom
feet
Genitals: females (bicornate or septate
uterus); males (cryptorchidism, small
scrotom)
Trisomy 13
 Associated Anomalies
Cardiac: VSDs, dextroposition, PDA
Renal abnormalities: cystic kidneys
Holoprosencephaly
Cutaneous hemangiomas
Seizure activity
Severe deficits in cognitive & motor
development
Trisomy 13
 Complications
Life expectancy: ~130 days, though 14%
survive to 1 year of age
Care is supportive
Education & support for parents is
essential!
Trisomy 18
 Etiology
Advanced maternal age
Most affected fetuses are female (4:1)
47 Chromosomes (3 of chromosome
18)
90% occur due to nondisjunction
during meiosis
Trisomy 18
 Presentation
Growth deficiency
Head: microcephaly with prominent
occiput
Eyes: microphthalmia with narrow
palpebral fissures, colobomas, corneal
opacities, hypoplasia of orbital ridges,
ptosis of one or both eyes
Ears: low-set, poorly developed, often
cup-shaped with large pinna, atresia of
auditory canal
Trisomy 18
 Mouth: micrognathia, microstomia, higharched palate
 Skin: excessive skin at nape of neck,
widely-spaced nipples, decreased dermal
creases due to decreased fetal
movement
Trisomy 18
 Musculoskeletal: clenched hand with index
finger overlapping middle finger &/or 5th
finger overlapping 4th finger, hypoplastic
nails, rocker-bottom feet, prominent heels,
hammertoes, syndactyly between 2nd & 3rd
toes, short sternum with slender ribs, narrow
pelvis with hip dysplasia
Trisomy 18
 Associated findings
Cardiac abnormalities: various (VSD,
PDA, pulmonary stenosis, coarctation of
the aorta, etc.)
Renal anomalies: horseshoe kidneys,
ectopic kidneys, double ureters, cystic
kidneys
Genital abnormalities: cryptorchidism in
males, hypoplasia of labia & prominent
clitoris in females
Umbilical hernias
Severe psychomotor retardation
Trisomy 18
 Complications/Outcomes
90% mortality rate within 1st year of life
Anomalies are multiple & severe
Treatment is supportive
Parental Education, support, &
involvement are essential!
Trisomy 18
Trisomy 21
 Etiology
Risk increases with maternal age though
~3/4 are born to mothers <35
47 chromosomes ( 3 of chromosome 21)
95% are complete trisomies; 2% are
mosaics; 3% are translocations
 Presentation
Head: small, round skull with flat occiput;
flat facies due to lack of orbital ridges; flat
nose; micrognathia
Trisomy 21
Eyes: upward slanting of palpebral
fissures, Brushfield spots on iris,
colobomatous cataracts, glaucoma,
prominent epicanthal folds
Ears: low-set, boxy ears
Mouth: narrow, short palate; large
protruding tongue
Skin: excess skin at nape of neck
Trisomy 21
 Presentation
Musculoskeletal: general hypotonia with
poor Moro reflex; hyperflexibility of joints;
square hands with short fingers;
transverse palmar crease; 5th fingers are
short & curve inward due to absent or
hypoplastic middle phalanx; low-set
thumbs with greater than usual
separation from index fingers
Trisomy 21
 Presentation (Musculoskeletal):
 broad, short feet with wide space
between great toe & 2nd toe & deep
creases that curve toward medial edge of
foot; short stature; dysplasia of pelvis with
narrow acetabular angle
Trisomy 21
 Associated findings
Prematurity
Mental retardation
Cardiac abnormalities: endocardial
cushion defects (AV canal), VSD, PDA
GI: duodenal atresia/stenosis, imperforate
anus
Hematologic: increased WBC count,
polycythemia, congenital leukemia
Endocrine: hypothyroidism
Trisomy 21
 Complications/Outcomes
Affected infants are mildly to severely
retarded (IQs range from 25-70)
Parent education & support are essential
for continuing treatment of common
health issues
Frequent URIs & ear infections
Cardiac sequelae, including CHF
Developmental delays
Trisomy 21
References
Brodsky, D. & Martin, C. (2003). Neonatology
Review. Hanley & Belfus, Inc.:
Philadelphia.
Kenner, C. & Lott, L.W. (2007).
Comprehensive Neonatal Care: An
Interdisciplinary Approach (4th Edition).
Saunders: St. Louis.
Siegfried, D.R. (2002). Anatomy & Physiology
for Dummies. Wiley Publishing Inc:
New York.
References
Thompson, G. (Ed). (2009). Anatomy &
Physiology Made Incredibly Visual.
Ambler, PA: Lippincott Williams &
Wilkins.
Verklan, M.T. & Walden, M. (2004). Core
Curriculum for Neonatal Intensive Care
Nursing (3rd Edition). Elseiver Saunders:
St. Louis.
References
www.ncbi.nlm.gov/About/primer/microarrays.ht
ml
www.ncbi.nlm.gov/books/bv.fcgi?ridhmg.section.196
http://en.wikipedia.org/wiki/mosaic_(genetic)
http://en.wikipedia.org/wiki/chromatin