Progeria

1
Progeria

• By Ann Lehto and Lekha Nair

2
History

• Progeria is derived from the Greek word meaning
  'prematurely old
• It is also known as Hutchinson-Gilford syndrome,
  because Jonathan Hutchinson and Hastings Gilford
  discovered the syndrome in 1886
• Around 100 cases have been identified since its
  discovery

3
Onset and Signs of Progeria

• At birth, the child appears normal. The first
  symptoms of Progeria are generally presented at
  6-12 months, when the child fails to gain weight,
  lose hair and have changes in skin conditions.
• The child begins to look old having narrowed
  face, conspicuous scalp veins and a pinched nose.
  
• There is high risk of delayed tooth formation.
  Generally, the limbs shows fragility accompanied
  with joint stiffness.

4
Symptoms of Progeria

• Growth failure during the first year of life
• Narrow, shrunken or wrinkled face with beaked
  nose
• Baldness, in addition to loss of eyebrows and
  eyelashes
• Prominent eyes
• Short stature
• Large head for size of face (macrocephaly)
• Open soft spot (fontanelle)
• Small jaw (micrognathia)
• Dry, scaly, thin skin
• Limited range of motion
• Teeth - delayed or absent formation
• High pitched voice
• All children have a similar appearance,
  regardless of ethnic background.

5
Treatment and Prognosis

• There is no cure for Progeria.
• Regular monitoring for cardiovascular disease may
  help with managing your child's condition. Some
  children undergo coronary artery bypass surgery
  or dilation of cardiac arteries (angioplasty) to
  slow the progression of cardiovascular disease.
• Certain therapies may ease some of the signs and
  symptoms. They include
• Low-dose aspirin a daily dose may help prevent
  heart attacks and stroke
• Physical and occupational therapy - to help with
  joint stiffness and hip problems, and allow the
  child to remain active
• High-calorie dietary supplements - including
  extra calories in the child's daily diet may help
  prevent weight loss and ensure adequate nutrition
• Extraction of primary teeth - the child's
  permanent teeth may start coming in before his or
  her baby teeth fall out. Extraction may help
  prevent overcrowding and developing a second row
  of teeth when permanent teeth come in.

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Prognosis

• Progeria is associated with a short lifespan
• The average patient survives to the early teens
  (around 13), however some patients have lived up
  to 30 years
• The cause of death is usually caused by stroke or
  heart problems, as a result of the progressive
  atherosclerosis (hardening of arteries)

7
Diagnosis

• Some signs of Progeria that can be tested
• Insulin-resistant diabetes doesnt respond
  readily to insulin injections
• Skin changes where connective tissue becomes hard
  and tough
• Cardiac stress testing can show signs of
  atherosclerosis of blood vessels- where fatty
  material collects along walls of arteries. This
  disorder is commonly associated with Progeria,
  and can be life threatening.
• The symptoms are unique to the disorder, and
  often it is diagnosed when the symptoms are shown
  at a young age.

John Tacket, 15
8
Inheritance

• Caused by a mutation of the LMNA gene
• Lamin A/C- produces proteins called lamins
• Lamins- structural proteins called intermediate
  filament proteins, which is important in the
  structure of the nuclear lamina
• Because the disorder is caused by a genetic
  mutation it is usually not inherited, and because
  the individual usually dies in their teens it
  cannot be passed on further.
• The disorder is rarely inherited from parents,
  but it can occur in children of consanguineous
  parents as a recessively inherited gene

9
The Mutation

• Mutation changes nucleotide in DNA sequence in
  gene- changes the cytosine to thymine in
  nucleotide 1824
• Mutation in lamin A results in abnormal lamin
  protein called progerin, which is missing 50
  amino acids on the end
• When mutated protein is incorporated into nuclear
  lamina, it prevents normal assembly of nuclear
  lamins- causes abnormal nuclear shapes
• Buildup of damaged protein can cause cells to die
  prematurely

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Pedigree
This pedigree of a girl from Italy with
consanguineous parents (second cousins)
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Interesting Facts

• There are 54 known children in 30 countries with
  Progeria, and 97 of the children are Caucasian.
• Progeria is a rare sporadic disorder with an
  incidence of 1 per 8 million live births.
• 90 percent of progeria patients die by age 13
  from fatal heart attacks or strokes.
• The mutation is believed to occur in the fathers
  sperm before conception.
• In spite of their physical ailments, children
  with Progeria have normal intellectual
  development. At school they are bright and
  inquisitive children.
• A child with Progeria, Mickey Hays, appeared in a
  movie playing an alien character -
  http//www.youtube.com/watch?vllHgPR2wie8
• Researchers have discovered that the toxic
  protein responsible for progeria is actually
  produced at low levels in all humans, possibly
  accumulating as we age. Bystudying children with
  progeria, we can further our understanding of a
  major mechanism of human aging and maybe find new
  ways to slow the process.

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Questions

• What is Progeria, essentially?
• What are some of the signs and symptoms of
  Progeria?
• What can a child with Progeria anticipate about
  his or her life?
• How does a child get Progeria?
• What is another disorder that is often associated
  with Progeria and can be tested?

13
Works Cited

• "Progeria." MayoClinic.com. 24 Apr 2009. Mayo
  Foundation for Medical Education and Research
  (MFMER), Web. 10 Jan 2010. lthttp//www.mayoclinic.
  com/health/progeria/DS00936gt.
• "About Progeria." 2006. The Progeria Research
  Foundation, Web. 10 Jan 2010. lthttp//www.progeria
  research.org/about_progeria.htmlgt.
• "Learning About Progeria." 10 Apr 2009. National
  Human Genome Research Institute, Web. 9 Jan 2010.
  lthttp//www.genome.gov/11007255gt.
• "LMNA". Genetics Home Reference. January 7, 2010
  lthttp//ghr.nlm.nih.gov/genelmnagt.
• Paradisi, Mauro. "Dermal fibroblasts in
  Hutchinson-Gilford progeria syndrome with the
  lamin A G608G mutation have dysmorphic nuclei and
  are hypersensitive to heat stress". BMC Cell
  Biology. January 7, 2010 lthttp//www.biomedcentral
  .com/1471-2121/6/27gt.
• "Hutchinson-Gilford Progeria". eMedicine. January
  8, 2010 lthttp//emedicine.medscape.com/article/111
  7344-overviewgt.
• "Progeria". The New York Times. January 8, 2010
  lthttp//health.nytimes.com/health/guides/disease/p
  rogeria/overview.htmlgt.
• Juncosa, Barbara. "New Hope for Progeria Drug
  for Rare Aging Disease". Scientific American.
  January 9, 2010 lthttp//www.scientificamerican.com
  /article.cfm?idnew-hope-for-progeria-drug-for-rar
  e-aging-disease gt.