Human Genetic Disorders

1
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 Smiths Recognizable Patterns of
  Human Malformation, Chromosome Abnormalities, and
  Genetic Counseling, Genetics In Medicine.

2
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.

3
Human Genetics

• Heredity
• The passing-down of traits from parent to child
  through genes, which are located in chromosomes.

Gene
4

• Pedigree
• A diagram that shows the pattern of inheritance
  of a gene in a family.

5

• Sex-Linked Traits
• Traits carried by X or Y chromosome
• Example Colorblindness .. Carried on X chromosome

genotypes
Why is it more common in males?
6
Genetic Disorders

• Types of Genetic Disorders
• Autosomal Recessive Genetic Disorders
• Autosomal Dominant Genetic Disorders
• Nondisjunction Genetic Disorders
• Sex-Linked Nondisjunction Genetic Disorders

7
Autosomal Recessive Genetic Disorders
Cystic fibrosis
Galactosemia
Phenylketonuria
(118000)
(155000)
(13900)
On chromosome 7
On chromosome 12
On chromosome 9
Affects ability to break down galactose
affects how body breaks down protein.
Affects respiratory / digestive sys.
Mutation in gene that affects salt movement, thus
produces thick sticky mucous on outside of cell.
This mucous clogs airways
Lack enzyme called GATL (which converts galactose
into glucose). Galactose build up in the blood.
prevents liver enzyme (PAH) from breaking down
phenylalanine., which builds up in blood
poisons nerve cells in brain.
8
Autosomal DominantGenetic Disorders
Breast Cancer
Colon Cancer
Huntington's
(5-10 of patients)
(130000)
(80 of patients)
On chromosome 17 or 13
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--high-risk, because may have inherited one
rare genetic condition FAP (familial adenomatous
polyposis).
Rarely inherited but can inherit gene
have a high of CAG triplets (gt40). Somehow brain
cells accumulate clumps of protein that become
toxic. Some patients lose gt 25 of their brain
cells before they die.
9
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

10
Nondisjunction

• When chromosomes don't separate properly during
  meiosis.
• results in gametes w/ too many or few
  chromosomes.

11
Nondisjunction Genetic Disorders

• Downs syndrome/Trisomy 21
• Patau syndrome/Trisomy 13
• Edwards syndrome/Trisomy 18

12
Trisomy 21 / Down Syndrome
(1800)

• 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

13
Trisomy 21
14
Trisomy 13 Patau syndrome
(110000)

• 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

15
Trisomy 13
16
Trisomy 18- Edwards syndrome
(13000)

• 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)

17
Trisomy 18
18
Trisomy Disorders

• Almost all other trisomy situations result in
  death of the fetus
• Trisomy means there are 3 chromosomes in one
  location

19
Triploidy and Tetraploidy

• 1-2 of all pregnancies
• Scarcely any triploids are born alive
• Arise from double fertilization

20
Sex linked Nondisjunction Genetic Disorders

• Turner syndrome
• Klinefelter syndrome
• Fragile-X syndrome

21
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

22
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

23
Turner Syndrome
24
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

25
Klinefelter Syndrome
26
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

.
27
Fragile X Syndrome
28
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.

29
General Human Genetic Disorders
30
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

31
Achondroplasia
32
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)

33
Marfan Syndrome
34
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

35
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

36
Progeria Syndrome
37
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)

38
FAS (Fetal Alcohol Syndrome)

• Maternal alcohol consumption
• Major cause of mental retardation
• Growth retardation
• Skeletal defects
• Heart defects

• Flat fultrum
• enlarged head
• neurological disorders

39
FAS
40
(No Transcript)
41
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

42
Taysachs

• 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

43
Taysachs
3-5 year old with advanced Taysachs Goggle.com
44
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.

45
Phenylketonuria (PKU)
46
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. Angelmans
  Syndrome

47
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

48
Angelmans Syndrome

• Happy Puppets disorder
• Mental Retardation
• Can understand only simple commands
• Inappropriate laughter

49
This is the end.

• Use your knowledge to be compassionate and kind
  towards others.