Human Genetic Disorders
• The following is a presentation of several human
genetic disorders. Some of the pictures may be
disturbing. Please keep in mind that these
photographs are taken to assist the medical field in
correctly diagnosing genetic disorders.
• Photos are from Smith’s Recognizable Patterns of Human
Malformation, Chromosome Abnormalities, and Genetic
Counseling, Genetics In Medicine.
Human Genetic Disorders
• Many of the disorders that will be discussed
during this presentation are in extremely
low frequency in the population. This
means that very few individuals in the
world suffer from these disorders.
• Heredity
Human Genetics
• The passing-down of traits from parent to child
through genes, which are located in
chromosomes.
Gene
• Pedigree
• A diagram that shows the pattern of
inheritance of a gene in a family.
• Sex-Linked Traits
• Traits carried by X or Y chromosome
• Example: Colorblindness .. Carried on X
chromosome
genotypes…
XiXi
X iY
X BXi
X BY
X BX B
Why is it
more
common in
males?
Genetic Disorders
• Types of Genetic Disorders
• Autosomal Recessive Genetic Disorders
• Autosomal Dominant Genetic Disorders
• Nondisjunction Genetic Disorders
• Sex-Linked Nondisjunction Genetic Disorders
Autosomal Recessive Genetic Disorders
Cystic
fibrosis
(1:3900)
Phenylketonuria
Galactosemia
(1:18000)
(1:55000)
On chromosome 7
On chromosome 12
On chromosome 9
Affects respiratory /
digestive sys.
affects how
body breaks
down protein.
Affects ability to
break down
galactose
Mutation in gene
that affects salt
movement, thus
produces thick sticky
mucous on outside of
cell. This mucous
clogs airways
prevents liver enzyme
(PAH) from breaking
down phenylalanine.,
which builds up in blood &
poisons nerve cells in
brain.
Lack enzyme called
GATL (which
converts galactose
into glucose).
Galactose build up
in the blood.
Autosomal DominantGenetic Disorders
Breast
Cancer
(5-10% of patients)
On chromosome 17
or 13
Rarely inherited …
but can inherit gene
Huntington's
Colon Cancer
(1:30000)
(~80% of patients)
On chromosome 4
On chromosome 5
brain disorder that
affects a person's
ability to think,
talk, and move.
Have family history
– at greater risk ;
risk increases
when a relative got
it before 50--highrisk, because may
have inherited one
rare genetic
condition: FAP
(familial
adenomatous
polyposis).
have a high #of CAG
triplets (>40). Somehow
brain cells accumulate
clumps of protein that
become toxic. Some
patients lose > 25% of
their brain cells before
they die.
Aneuploidy
• Abnormal number of chromosomes
• Trisomy disorders are considered major chromosomal
abnormalities that involve the addition of an extra
chromosome or part of a chromosome. Most individuals
will only have two copies of a single chromosome one that
was received from Mom and one received from Dad.
• These disorders are caused by a nondisjunction during the
process of meiosis and other factors.
• 1/5 of all conceptions and about 1/2 of all spontaneous
abortions have chromosome abnormalities
Nondisjunction
• When chromosomes don't separate properly during
meiosis.
• results in gametes w/ too many or few chromosomes.
Nondisjunction Genetic Disorders
• Downs syndrome/Trisomy 21
• Patau syndrome/Trisomy 13
• Edwards syndrome/Trisomy 18
Trisomy 21 / Down Syndrome
(1:800)
• Individuals have partial or total addition of
chromosome number 21
• Symptoms
–
–
–
–
–
Mental retardation
distinctive eyes
enlarged tongue
short stature
enlarged heart
low body tone
decreased life expectancy small ears
Slanted palpebral Fissures Flat face
Trisomy 21
Trisomy 13 – Patau syndrome
(1:10000)
• Symptoms
– defects of eye, nose,
lip, and forebrain
– Polydactyly (more then
5 fingers or toes)
– hyperconvex
fingernails (arches
down)
• Only 18% survive the
first year
• Survivors have severe
mental defects
• seizures
Trisomy 13
Trisomy 18- Edwards syndrome
(1:3000)
• Clenched hand
• Distinct patterns on the
fingertip
• Low Arch Dermal - the
crease on tip the 5th finger
is missing.
• 80% die w/in first two
months
• Only 10% survive the first
year
• Usually feeble (weakness)
• Limited capacity for
survival
• Resuscitation (artificial
breathing) often
performed at birth
• apneic episodes neonatally
(stop breathing during
sleep)
Trisomy 18
Trisomy Disorders
• Almost all other trisomy situations result in
death of the fetus
• Trisomy means there are 3 chromosomes in
one location
Triploidy and Tetraploidy
• 1-2% of all
pregnancies
• Scarcely any triploids
are born alive
• Arise from double
fertilization
Sex linked Nondisjunction Genetic Disorders
• Turner syndrome
• Klinefelter syndrome
• Fragile-X syndrome
Sex Chromosome Abnormalities
• A normal female has two X chromosomes
• A normal male has an X and a Y
chromosome
• There are several disorders where additional
sex chromosomes are present
Turner Syndrome
• Females with only one X sex chromosomes
• Physical Characteristics
–
–
–
–
–
–
–
Short stature
Web neck
Infertile
Normal intelligence
Low posterior hairline
broad chest with widely spaced nipples
elevated frequency of renal (kidney) and cardiovascular
anomalies
Turner Syndrome
Klinefelter Syndrome
•
•
•
•
•
•
•
XXY
First sex chromosome abnormality to be reported
Tall, thin relatively long legs
appear normal until puberty
Hypogonadism (sex hormones are not released)
Infertile due to undeveloped sex orgnas
significantly reduced IQ
Klinefelter Syndrome
Fragile X Syndrome
• In males the lower portion of the X chromosome appears
constricted in a karyotype.
• Moderate mental retardation
• Fragile site - chromatin fails to condense during mitosis
• Females who carry the trait may also show
symptoms
• long face with a prominent jaw, large prominent ears,
high arched palate; flattened nasal bridge; Prominent
forehead
Fragile X Syndrome
Fragile x syndrome is like Autism
• Developmental delay, speech delay, short attention span or
hyperactivity, mouthing of objects persisting at an age
beyond expected, difficulty in disciplining the child,
frequent temper tantrums, autistic-like behaviors such as
rocking, talking to oneself, spinning, unusual hand
movements, difficulty with transitions, preference for
being alone, echolalia, poor eye contact; poor motor
coordination; history of vomiting, spitting up or colic
during infancy; history of self-abusive behavior; hand
flapping; drooling persisting beyond expected; increase
fighting with others; hand/thumb sucking.
General Human Genetic
Disorders
Achondroplasia
• Dwarfism- small
stature
• Large head
• Skeletal disorders
• Narrow nasal passages
• Respiratory problems
• 90% of cases are fresh
mutations
• Older paternal age is a
contributing factor to
mutation
Achondroplasia
Marfan Syndrome
•
•
•
•
•
Tall stature with long slim limbs
Low tone muscles
Little subcutaneous or skin fat
60% scoliosis
Heart disorders (thought that Abraham
Lincoln had this disorder)
Marfan Syndrome
Progeria Syndrome
• Hutchinson-Gilford Progeria
Syndrome or premature aging
disease.
• Noticeable 18-24 months of
age.
• Life expectancy 8-21 years
with an average of 14 years
• Research on these individuals
are done to help us
understand the aging process
Progeria Syndrome
•
•
•
•
•
Aged looking skin
Growth failure
Hip dislocation
Arthritis, joint stiffness
Cardiovascular atherosclerosis disease and stroke,
eventually leading to death.
• Enlarged heart and high blood pressure
• Not specific to sex or ethnicity
Progeria Syndrome
Taratogens
• Any agent that can produce a malformation
or raise the population incidence of a
malformation.
• Most known teratogens are infectious
agents, radiation or drugs (alcohol, cocaine,
Tetracycline and Streptomycin- antibiotic,
Anticonvulsants)
FAS (Fetal Alcohol Syndrome)
• Maternal alcohol
consumption
• Major cause of mental
retardation
• Growth retardation
• Skeletal defects
• Heart defects
– Flat fultrum
– enlarged head
– neurological disorders
FAS
Metabolic Disorders
• These disorders are characteristic of a
breakdown of a biochemical pathway which
can cause minor problems or major
problems.
• Several of these disorders
Tay’sachs
• Blindness
• Severe mental and
physical deterioration
(normal to 6 months).
• A missing enzyme causes
progressive nerve cell
damage.
• Leading to seizures and
paralysis.
• Death in early childhood
by 5 years of age.
• Lethal autosomal
recessive disorder with
high frequency in a
specific, genetically
isolated population
• first disorder where large
scaled screening was
performed
Tay’sachs
3-5 year old with advanced Taysachs
Goggle.com
Phenylketonuria (PKU)
• Autosomal recessive trait.
• Causes severe mental
retardation, skin rashes,
irritable behavior, musty
body odor.
• Cannot degrade the amino
acid phenylalanine which
accumulates in body fluids
preventing the brain from
growing and developing
normally.
• 1/10,000 live births
• Colorado performs a
mandatory test for all
newborns (heal prick)
• A strict non-animal
protein diet must be
followed (eggs, meat, milk
etc.) throughout
adolescence and possibly
adulthood.
• Blood is monitored for
ones whole life.
Phenylketonuria (PKU)
Genomic Imprinting
• The expression of the disease phenotype
depends on whether it has been inherited
from the father or from the mother.
• Prader-Willi Syndrome vs. Angelman’s
Syndrome
Prader-Willi Syndrome
•
•
•
•
•
Obesity
Small hands and feet
Short stature
Mental retardation
Do not produce the chemical
that tells them they are full
• Severely over weight
• Their crave for food can be so
server that parents have to lock
their refrigerators
• Inherited from the mother
Angelman’s Syndrome
• “Happy Puppets”
disorder
• Mental Retardation
• Can understand
only simple
commands
• Inappropriate
laughter
This is the end….
Use your knowledge to be
compassionate and kind towards
others.