Human Genetic Disorders

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Human Genetic Disorders

• 2005
• Ruth Boldivia
• Updated 2006 by Weller and Polage

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Human Genetic Disorders

• Photos are from Smiths Recognizable Patterns of
  Human Malformation, Chromosome Abnormalities, and
  Genetic Counseling, Genetics In Medicine.
• Many of the disorders that will be discussed
  during this presentation are in extremely low
  frequency in the population.

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Aneuploidy

• Abnormal number of chromosomes
• Trisomy disorders 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

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Trisomy 21 also known as Down Syndrome or
Mongoloidism

• 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

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Trisomy 21
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Trisomy 13 Patau syndrome

• 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

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Trisomy 13
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Trisomy 18- Edwards syndrome

• 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)

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Trisomy 18
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Trisomy Disorders

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

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Triploidy and Tetraploidy

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

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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

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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

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Turner Syndrome
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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

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Klinefelter Syndrome
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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

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Fragile X Syndrome
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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.

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General Human Genetic Disorders
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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

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Achondroplasia
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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)

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Marfan Syndrome
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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

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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

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Progeria Syndrome
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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)

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FAS (Fetal Alcohol Syndrome)

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

• Flat fultrum
• enlarged head
• neurological disorders

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FAS
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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

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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

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

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Phenylketonuria (PKU)
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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

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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

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Angelmans Syndrome

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

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This is the end.

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