Genetic Disorders

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Genetic Disorders
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Achondroplasia

• Mode of Inheritance Autosomal Dominant
• Most people with achondroplasia are Heterozygous.
  The homozygous condition is fatal.
  
• Results from a mutation on the 4th chromosome
• Common name- short limbed dwarfism
• Symptoms
• Short arms and legs when compared to the trunk
• Large head
• Prominent foreheads
• Incidence
• Occurs equally in males and females and in all
  races
  
• 1/25,000 children

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Cri Du Chat

• Symptoms
• high-pitched cry sounds like a cat (for which the
  syndrome was named)
  
• low birth weight and slow growth
• small head (microcephaly)
• wide-set eyes (hypertelorism)
• downward slant to the eyes (palpebral fissures)
• small jaw (micrognathia)
• low-set ears (may be malformed)
• partial webbing or fusing of fingers or toes
• single line in the palm of the hand (simian
  crease)
  
• mental retardation
• slow or incomplete development of motor skills
• Mode of Inheritance - Spontaneous deletion of
  segment of chromosome 5
  
• Incidence between 1/20000 and 1/50000 babies
• Prognosis dependent on the severity of mental
  retardation
  

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Cystic Fibrosis

• Symptoms
• Chronic lung problems
• Digestive disorders
• Lungs are covered with a thick sticky mucus which
  is hard to remove. This promotes bacterial
  infections.
  
• The reason the mucus is thick, is that the body
  is unable to transport water and salt across the
  cell membrane

• Mode of Inheritance
• Autosomal recessive for CFTR gene
• Most common in Europeans

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• Diagnosis
• People with cystic fibrosis have 2-5 times the
  normal amount of salt in their sweat. Doctors use
  a sweat test to measure the amount of salt in a
  person's sweat. Sweat is collected from the arm
  or leg and taken to a laboratory to be analyzed.
• In newborns, doctors measure the amount of a
  protein called trypsinogen in the blood. The
  level is higher in people with CF.
  
• Finally, genetic tests can identify a faulty CFTR
  gene using a sample of the patient's blood.
  
• Treatment
• There is no cure for cystic fibrosis. Common
  treatments are
  
• Chest physical therapy, in which the patient is
  repeatedly clapped on the back to free up mucous
  in the chest
  
• Inhaled antibiotics to kill the bacteria that
  cause lung infections
  
• Bronchodilators (also used by people with asthma)
  that help keep the airways open
  
• Pancreatic enzyme replacement therapy to allow
  proper food digestion
  
• Gene therapy (a treatment currently in clinical
  trials), in which the healthy CFTR gene is
  inserted into the lung cells of a patient to
  correct the defective gene.

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Duchene Muscular Dystrophy

• Symptoms
• Gradual wasting away of skeletal muscle
• Progressive and increased weakness and loss of
  muscle mass and function
  
• Noticed before age 5
• Pelvic and trunk muscles are affected 1st
• This results in spinal deformaties and a waddling
  gate
  
• Death usually occurs because of respiratory
  weakness and wasting away of the heart muscle
  

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• Mode of Inheritance - X linked recessive, boys
  are mostly affected
  
• Treatment Treatment may include physical
  therapy, respiratory therapy, speech therapy,
  orthopedic appliances used for support, and
  corrective orthopedic surgery. Drug therapy can
  slow muscle degeneration, control seizures and
  some muscle activity, delay some damage to dying
  muscle cells, and fight respiratory infections.
  Some patients may need assisted ventilation to
  treat respiratory muscle weakness and a pacemaker
  for cardiac abnormalities.
• Prognosis The prognosis for people with MD
  varies according to the type and progression of
  the disorder. Some cases may be mild and progress
  very slowly over a normal lifespan, while others
  produce severe muscle weakness, functional
  disability, and loss of the ability to walk. Some
  children with MD die in infancy while others live
  into adulthood with only moderate disability.

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Fibrodysplasia ossificans progressiva

• rare genetic disease that causes muscle to be
  turned into bone.
  
• Mode of Inheritance autosomal dominant, but most
  cases are sporadic.
  
• Symptoms any small injury to connective tissue
  (muscles, ligaments, and tendons) can result in
  the formation of hard bone around the damaged
  site. Children are born with a characteristic
  malformation of the great toes and begin to
  develop heterotopic (extra) bone formation during
  early childhood.

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Fragile X syndrome

• Symptoms
• Intellectual difficulties mental retardation
  patients have a long, narrow face prominent
  ears, jaw and forehead, loose joints patients
  usually avoid eye contact
• Emotional and behavioral problems are common such
  hand-biting, and hand flapping is common
  
• Common inherited cause of mental retardation
• The name comes from the broken appearance of the
  X chromosome in people with the disease.

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• Mode of Inheritance X linked recessive
• results in a break or weakness on the long arm of
  the X chromosome
  
• Treatment There is no cure for fragile X
  syndrome. 
  
• special education, speech and language therapy,
  occupational therapy and behavioral therapies are
  helpful in addressing many of the behavioral, and
  cognitive issues in fragile X syndrome.
• medications can be helpful for aggression,
  anxiety, hyperactivity and poor attention span.
  
• Testing
• The Southern Blot analysis -this determines if
  the gene has a full mutation and its approximate
  size, if the gene has been methylated and if
  there is mosaicism (a mixture of different cell
  types).
• The polymerase chain reaction (PCR) analysis can
  determine the actual number of repeats in
  individuals with a normal size gene or with a
  premutation. It is not the test of choice to
  diagnose a full mutation, but is quite accurate
  in determining premutation and normal gene repeat
  numbers.

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Klinefelters Syndrome

• Symptoms
• have internal male ducts and genitalia but
  underdeveloped testes that fail to produce sperm
  feminine sexual development is not suppressed, so
  these men have slightly developed breasts
• Mode of Inheritance Trisomy of sex chromosome
  XXY
  
• Remember these result due to nondisjunction
  during meiosis
  
•  

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• Diagnosis
• diagnosed in adulthood using a karyotype, an
  analysis of the patient's chromosomes taken from
  a blood sample.
  
• also be diagnosed during a woman's pregnancy.
  Doctors can look for the chromosome abnormality
  in cells taken from the amniotic fluid that
  surrounds the fetus (amniocentesis), or from the
  placenta (chorionic villus sampling (CVS)).
• Treatment
• Hormone replacement therapy is the best way to
  treat this disorder. Teenagers are typically
  given testosterone injections to replace the
  hormone that would normally be produced by the
  testes. Synthetic testosterone works like natural
  testosterone - it builds muscle and increases
  hair growth.

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Marfan Syndrome

• Symptoms
• A connective tissue disorder involving collagen
  may affect the heart, blood vessels, lungs, eyes,
  bones, and ligaments. Patients are tall slender,
  loose jointed have sclerosis, and the breastbone
  is usually caved in. The face is long and narrow
  and the roof of the mouth is high, and the teeth
  are crowded. The heart frequently murmurs, the
  aorta is weak, and nearsightedness is very
  common
• Mode of Inheritance Autosomal daominant
• It is thought that Abraham Lincoln had Marfan
  Syndrom
  
• Treatment - no cure for the Marfan syndrome.
• MedicationBeta-blocker medications have been
  shown to slow enlargement of the aorta and delay
  aortic surgery.
  
• Heart surgery
• Lifestyle changesLifestyle changes, such as
  avoiding strenuous exercise and contact sports,
  can help contribute to living with Marfan
  syndrome.

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Neurofibromatosis

• NF1 affects the peripheral nervous system and NF2
  affects the central nervous system
  
• Mode of inheritance NF1 is caused by a mutation
  on chromosome 17 and NF2 is caused by a mutation
  on chromosome 22
  
• Symptoms
• NF2- Growth around the vestibular nerve of the
  ear which causes deafness and in central nervouse
  system, brain, and spinal cord
  
• NF1- Pigmented spots on skin and bone
  abnormalities
  
• Treatments- surgeries to remove growths

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Osteogenisus Imperfecta

• genetic disorder characterized by bones that
  break easily, often from little or no apparent
  cause.
  
• caused by a genetic defect that affects the
  bodys production of type I collagen. Collagen is
  the major protein of the bodys connective tissue
  and can be likened to the framework around which
  a building is constructed.
• It is often, though not always, possible to
  diagnose OI based solely on clinical features.
  Clinical geneticists can also perform biochemical
  (collagen) or molecular (DNA) tests that can help
  confirm a diagnosis of OI in some situations.
  These tests generally require several weeks
  before results are known. Both the collagen
  biopsy test and DNA test are thought to detect
  almost 90 of all type I collagen mutations.
• A positive type I collagen study confirms the
  diagnosis of OI, but a negative result leaves
  open the possibility that either a collagen type
  1 mutation is present but was not detected or the
  patient has a form of the disorder that is not
  associated with collagen type 1 mutations.
  Therefore, a negative type I collagen study does
  not rule out OI.

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Phenylketonuria PKU

• Phenylketonuria is a rare metabolic disorder that
  affects the way the body breaks down protein. If
  not treated shortly after birth, PKU can be
  destructive to the nervous system, causing mental
  retardation.
• PKU is caused by a mutation in a gene on
  chromosome 12. The gene codes for a protein
  called PAH (phenylalanine hydroxylase), an enzyme
  in the liver. This enzyme breaks down the amino
  acid phenylalanine into other products the body
  needs. When this gene is mutated, the shape of
  the PAH enzyme changes and it is unable to
  properly break down phenylalanine. Phenylalanine
  builds up in the blood and poisons nerve cells
  (neurons) in the brain.
• Mode of Inheritance Autosomal recessive

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• Diagnosis
• Because PKU must be treated early, babies in
  every U.S. state are routinely tested for the
  disease. A small blood sample is taken from the
  baby's heel or arm and checked in a laboratory
  for high levels of phenylalanine.
• Treatments
• People who have PKU must eat a protein-free diet,
  because nearly all proteins contain
  phenylalanine. Infants are given a special
  formula without phenylalanine. Older children and
  adults have to avoid protein-rich foods such as
  meat, eggs, cheese, and nuts. They must also
  avoid artificial sweeteners with aspertame, which
  contains phenylalanine.

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Prader-Willi Syndrome

• complex genetic disorder that typically causes
  low muscle tone, short stature, incomplete sexual
  development, cognitive disabilities, problem
  behaviors, and a chronic feeling of hunger that
  can lead to excessive eating and life-threatening
  obesity.
• due to lack of several genes on one of an
  individuals two chromosome 15s the one normally
  contributed by the father. In the majority of
  cases, there is a deletionthe critical genes are
  somehow lost from the chromosome. In most of the
  remaining cases, the entire chromosome from the
  father is missing and there are instead two
  chromosome 15s from the mother (uniparental
  disomy). Mode of Inheritance spontaneous
  genetic mutation

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Sickle Cell Anemia

• A red blood cell disorder where cells become hard
  and sticky they appear to look like sickles.
  They clog the flow of blood and often break apart
  , causing severe pain, damage, and low blood
  count (anemia).
• The cells sickle because there
• is a change in the hemoglobin
• to form long rods when
• oxygen is given up.
• Mode of Inheritance
• autosomal recessive

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• Diagnosis
• tests can show if the newborn infant has sickle
  cell anemia or carries the sickle cell trait. If
  the test shows that the sickle-shaped hemoglobin
  is present, a second blood test is done to
  confirm the diagnosis.
• sample of amniotic fluid or tissue taken from the
  placenta. This test can be done as early as the
  first few months of pregnancy.
  
• Treatments
• A bone marrow transplant is the only cure
• The drug hydroxyurea lessens complications
• Blood transfusions
• Narcotics for pain

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Tay Sachs

• Symptoms
• Mental retardation, infants become weak and have
  a difficult time eating, loss of motor function
  a delay in learning to sit or stand a typical
  cherry red spot on the retina at 12 months there
  is a decrease in mental and motor functions ,
  onset of blindness, deafness, rigidity and brain
  enlargement death usually occurs by age 3 by
  pneumonia or lung infection
• Mode of Inheitance autosomal recessive
• Prevalent in Jews of Eastern-European descent
• Treatments
• No cure
• Treatment of the late onset form of Tay-Sachs
  with a ganglioside synthesis inhibitor
  

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Trisomy 21 Down Syndrome

• Symptoms
• Small stature
• Mild to moderate mental retardation
• Delayed mental and motor development
• Smaller ears and mouth
• Smaller hands and feet
• Decreased muscle tone
• Gap between 1st and 2nd toes
• Mode of Inheritance
• 95 have trisomy 21 Remember this means that
  the individual has 47 chromosomes in each cell
  rather than 46.
  
• 3-4 have a translocation or an extra chromosome
  attached to another chromosome typically 14,21,
  or 22.

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Trisomy 18 Edwards Syndrome

• Symptoms
• Infants are small with elongated skulls
• ears are set low and are malformed
• webbed neck
• congenital dislocation of hips
• receding chin
• Prognosis Survival time is normally less than 4
  months. Death usually occurs from pneumonia or
  heart failure.
  
• Mode of Inheritance Trisomy 18
• Incidence 1/11,000, 80 are females

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Trisomy 13 Patau Syndrome

• Symptoms Infants are not mentally alert thought
  to be deaf tend to have a hairlip cleft palates
  are also common polydactly congenital
  malformation of most organ systems
• Most embryos with trisomy 13 do not survive
  gestation and are spontaneously aborted. Of those
  surviving to term gestation, approximately 82-85
  do not survive past 1 month , and 85-90 do not
  survive past 1 year of age. Of those infants that
  survive past 1 year, most have few major
  malformations, but the prognosis remains poor.
  There have been 5 cases reported in the medical
  history of patients living beyond 10 years of
  age.

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Turner Syndrome

• Symptoms
• females are short in stature , infertile there
  is no connection with mental retardation, only
  learning difficulties skeletal abnormalities,
  heart and kidney abnormalities thyroid
  disfunction the external genitalia are female,
  but the ovaries are rudimentary
• Mode of Inheritance
• Monosomy nondisjunction of sex chromosomes
  during meiosis
  
• Complete are partial absence of two X chromosomes
  (XO) mostly resulting in missing genetic
  material on the X chromosome
  

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• Diagnosis
• blood sample can be used to make a karyotype (a
  chromosome analysis) and the diagnosis can be
  confirmed.
  
• during pregnancy with a chorionic villus sampling
  (CVS) or amniocentesis. Alternatively, an
  ultrasound (a machine that uses sound waves to
  look inside a mother's uterus) can identify the
  disorder by its physical symptoms before the baby
  is born.
• Treatment
• Hormone replacement therapy is the best way to
  treat this disorder. Teenagers are treated with
  growth hormone to help them reach a normal
  height. They may also be given low doses of
  androgens (male hormones which females also
  produce in small quantities) to increase height
  and encourage normal hair and muscle growth. Some
  patients may take the female hormone estrogen to
  promote normal sexual development.