Congenital

& Genetic
Diseases
OBJECTIVES
❚ Differentiate among the terms
congenital, genetic, chromosomal,
environmental, and multifactorial
defects.
❚ Describe the inheritance pattern:
❙ Autosomal recessive disorders
❙ Autosomal dominant disorders
❙ X-linked recessive disorders
❚ Explain the common causes of
developmental disorders and their
relationship to fetal development
OBJECTIVES
❚ Describe the benefits and risks of
genetic screening programs and
prenatal testing.
❚ Discuss the purposes of genetic
engineering and current concerns.
❚ Describe the genetic defect in a child
with Down syndrome and the effects
on the child.
Origins of Modern Genetics
❚ Gregor Mendel
❚ Studied inheritance
of characteristics
in garden peas
Mendel’s First
Experiment
Mendel’s Conclusions
❚ Hereditary characters are determined by
discrete factors (GENES)
❚ Genes appear in pairs, one from each
parent
❚ Genes can occur in different forms
(ALLELE)
❚ If members of gene pair are different
(heterozygous), one allele will express
itself (dominant allele) and the other will
not (recessive allele)
Chromosomes
❚ Genetic information for each cell is
stored
❚ 23 pairs in each human cell
❚ 22 pairs are AUTOSOMES => shaped
in karyotype
❚ 23rd pair => pair of sex
chromosomes
❙ XY => male
❙ XX => female
PAIRING OF CHROMOSOMES:
Gender Identification
MALE FEMALE

X X Y X X Y
X X
Chromosomes
Chromosomes:
Carriers of
Genes
 Meiosis
 Each sperm and ovum
receive only 23
chromosomes

Zygote = 46
chromosomes (23 pairs
containing an assortment
of genetic information
inherited from the parents)
Mitosis
Deoxyribonucleic
Acid (DNA)
“file” that contains
information about
protein synthesis in
the cell
DNA Structure
 DNA
Replication
Genes and DNA
Ribonucleic
Acid

 Provides
communication
link with DNA
during the
actual synthesis
of proteins and
helps to
maintain control
of cell activity.
Protein
Synthesis
Protein Synthesis
 Protein
Structure
determines
Protein
Function
Molecular Biology’s Central Dogma

DNA

RNA

PROTEIN

FUNCTION STRUCTURE
CONGENITAL DEFECTS
❚ disorders present at birth
❙ GENETIC – may result from single-gene
trait or from chromosomal defect; may
be multifactorial.
❙ CHROMOSOMAL – usually result from
an error during meiosis, when the DNA
fragments are displaced or lost, thus
altering genetic information
❙ DEVELOPMENTAL – may result from
premature death, difficult labor &
delivery or exposure to teratogens
Mendelian Inheritance
❚ Autosomal
Recessive ❚ GENETIC
❚ Autosomal DISODERS
Dominant ❙ Single-gene
❚ X-linked Recessive disorders
❚ X-linked Dominant
❚ Y-linked
 HOMOZYGOUS

HETEROZYGOUS
Autosomal Recessive
❚ Either sex gets disease
❚ Siblings are usually affected, but not
parents
❚ Heterozygotes of both sexes normal
❚ Heterozygote parents have diseased kids
in ratio of 1:3
❚ If defect involves a rare gene parents may
be related
 PROBABILITY:

 25% Normal
 50% Carrier
 25% Affected

A.K.A: Storage disease

or Inborn Errors of
Metabolism
PROBILITY
 50% NON-
CARRIERS
 50% CARRIERS
Autosomal Recessive
❚ Galactosemia
❚ Tay-Sachs Disease
❚ Cystic Fibrosis
❚ Albinism
❚ Phenylketonuria (PKU)
❚ Sickle Cell Anemia
TAY-SACH’S DISEASE
❚ aka,
Sphingolipidosis
❚ deficiency of
hexosaminidase A,
resulting in apathy
and regression in
motor & social
development and
decreased vision.
❚ Prognosis: poor
(4y.o.)
CYSTIC FIBROSIS
❚ affects exocrine
glands, primarily
the lungs and
pancreas resulting
in altered viscosity
of mucus-secreting
glands throughout
the body.
SICKLE CELL DISEASE
❚ involves a
defective
hemoglobin (sickle-
shape) resulting to
joint pains and
swelling.
PHENYLKETONURIA (PKU)
❚ metabolic (liver)
enzyme
(phenylalanine
hydroxylase) w/c
metabolizes the
amino acid
phenylalanine.
{toxic to brain cells}
ALBINISM
❚ caused by the
absence of an
enzyme that
produces melanin
❚ results in a
complete lack of
pigmentation in
skin, hair, or eyes
GALACTOSEMIA

❚ the inability to
metabolize
lactose
Autosomal Dominant
❚ Affects males, females equally
❚ If you have the gene, you have the
disease
❚ Every affected individual has an affected
parent
❚ Normal siblings of affected individuals do
not transmit disease (no unaffected
“carriers”)
PROBABILITY
50%
AFFECTED
CHILD
PROBABILITY

 75% AFFECTED
 25% NORMAL
Marfan’s Syndrome
❚ Marfan patients
are tall, with very
long extremities.
❚ The arm span
exceeds the
height.
❚ Joints are hyper-
extensible
Huntington’s Disease
❚ Neurodegenarative
disorder
❚ pattern of
repetitive
abnormal
movements called
chorea
 Autosomal dominant

ACHOO Syndrome:
Compelling Heliopthalmic
Outburst

❚ sneeze
excessively,
approximately 30
to 40 times, in the
presence of
brightness.
Polydactyly

❚ More than the

number of digits.
Achondroplastic Dwarfism
❚ short stature,
usually reaching a
full adult height of
around 4'0" (1.2
meters).
❚ mutation in the
fibroblast growth
factor receptor
gene 3 (FGFR3),
which causes an
abnormality of
cartilage formation
X-linked Recessive
❚ Females
❙ 25% genetic carrier
❙ 25% normal
❚ Males
❙ 25% affected
❙ 25% normal
X-linked Recessive
❚ More frequent in males
❚ Passed from affected males through their
daughters
❚ No transmission directly from father to son
❚ Female carriers can express phenotype at
variable levels
X-linked Recessive

❚ Red/Green
Colorblindness
Duchenne Muscular
Dystrophy
❚ weakens the
muscles that assist
the body's
movements.
❚ have either
missing or mutated
genes that don't
produce the
proteins needed
for the muscles
Hemophilia
❚ HemophiliaA:caused by a deficiency
B (Christmas of active
disease):
clotting
caused factor
by a VIII (8).active clotting factor
lack of
IX
X-linked Dominant
❚ Females
❙ 50% carrier
❚ Males
❙ 50% normal
X-linked Dominant
❚ Affected males with normal spouses
have normal sons and all affected
daughters
❚ All offspring have 50% chance of
being affected
Y-linked

Father’s Gametes

X Y

X XX XY
Mother’s
Gametes
X XX XY
Y-linked

❚ Hairy ears
Non-Mendelian Inheritance
❚ Mitochondrial Traits
❙ Mitochondria contain multiple copies of
a single DNA strand
❙ All mitochondria transmit through ova
❙ Mitochondrial traits pass from mother to
child
❙ Disorders involve combinations of CNS,
eye, and muscle tissue abnormalities
Non-Mendelian Inheritance
❚ Multifactorial Inheritance
❙ Do not involve single genes
❙ Pedigrees do not exhibit Mendelian
patterns
❙ Frequently involve interaction between
host, environmental factors
Multifactorial Disorders

❚ Congenital
❙ Neural tube disorders
❙ Cleft lip, palette
❙ Congenital heart disease
Multifactorial Disorders
❚ Adult
❙ Coronary artery ❙ Asthma, allergies
disease ❙ Autoimmune
❙ Type I diabetes disorders
❙ Type II diabetes ❙ Bipolar disorder
❙ Breast cancer ❙ Schizophrenia
❙ Colon cancer ❙ Kidney stones
❙ Lung cancer ❙ Gallstones
❙ Rheumatic heart ❙ Obesity
disease ❙ Peptic ulcer disease
❙ Alcoholism ❙ Gout
 Coronary Artery Disease

Hypercholesterolemia
Blood pressure Diabetes mellitus
Cholesterol
Triglycerides Major Genes
HDL Background
Weight Genes
Glucose

Environmental Smoking
Factors Stress
Inactivity
Diet
Oral Contraceptives
Chromosomal
Abnormalities
Trisomy-21
Down’s Syndrome
❚ 1 in 600 births
❚ Short, broad nose
❚ Epicanthal fold
❚ Small oral cavity
❚ Large, furrowed
tongue
❚ Large, irregular
teeth
❚ IQs from 20 to 50
 Slanting palpebral
fissures and epicanthic
folds ("mongolism")
 Open mouth, big
tongue with no central
crease
BRUSHFIELD'S SPOTS
PALMAR (Simian) CREASE
Trisomy 13: Patau's syndrome
Patau’s Syndrome
❚ 1 in 20,000 births
❚ Sloping forehead
❚ Small head, eyes
❚ Cleft lip, palate
❚ Heart defects
❚ 75% die in first
year
❚ 100% by age 6
Trisomy 18
Edwards’ Syndrome
❚ 1 in 11,000 births
❚ Small mouth, jaw
❚ Low-set, malformed
ears
❚ Clinched fist, index
finger overlapping
3rd, 4th fingers
❚ Rocker-bottom feet
❚ Heart defects
❚ Hearing loss
❚ 90% die by age 1
Kleinfelter’s Syndrome
Kleinfelter’s Syndrome

❚ 1 in 500 males
❚ Taller than average
❚ Partial breast
development
❚ Small testicles, high-
pitched voice, female hair
distribution
❚ Altered body proportions,
hips slightly larger than
normal
Turner’s Syndrome
Turner’s Syndrome
❚ 1 in 2500 females
❚ Grow slowly
❚ Shield chest when young
❚ Low hair line
❚ Widely spaced nipples
❚ Fail to menstruate, no
ova
❚ Normal IQ; weakness in
math, spatial perception
❚ “cubitus valgus” (elbows
Small uterus flanked
by two streak ovaries
Streak ovary histology (right, no eggs), normal for
comparison (left, eggs)
Jacob’s Syndrome (XYY)
❚ “Super Male”
❚ 1 in 1000 males
❚ 1 in 50 in prison populations
❚ Excessively tall (2/3s > 6 feet)
❚ IQs around 80
❚ Low threshold for control of
aggression
X-Polysomy (XXX, XXXX)
❚ XXX, 1 in 1400 females
❚ Cannot be distinguished from XX
females
❚ Problems with spontaneous
abortions
❚ XXX have normal IQs, increasing
numbers cause mental deficiency
DEVELOPMENTAL DISORDERS

❚ Exposure to harmful influences in the

first 2 wks of life => DEATH OF THE
EMBRYO
❚ Critical time = first 2 months of
development
❚ Alcohol = FETAL ALCOHOL
SYNDROME
❚ Cigarette smoking = LOW
BIRTHWEIGHT
❚ Radiation
❚ Drugs (e.g. thalidomide)
❚ Maternal infections (German
measles)
❚ Mercury
TORCH
❚ routine prenatal screening test for
high risk maternal infections
❚ Toxoplasmosis, Other (Hep. B,
Mumps, Rubeola, Varicella,
Gonorrhea, Syphillis), Rubella,
Cytomegalovirus, and Herpes
SCREENING
❚ Family pedigree
❚ UTZ – gross defects
❚ Newborn Screening Test
❚ Amniocentesis
❚ Maternal blood screens
❙ Triple screen: AFP, beta unit hCG,
unconjugated estriol (uE3)
❙ Quadruple screen : + inhibin-A (Spina
bifida or Down syndrome)