Achondroplasia

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Achondroplasia

• By Kait Keaveny

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Achondroplasia

• Autosomal Dominant Disorder.
• Affects about 1 in 25,000 people.
• About 98 of those with achondroplasia have a
  point mutation in the FGFR3 gene at 4p16.3 that
  encodes fibroblast growth factor receptor 3.

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• The penetrance of the gene is 100
• The protein made by the FGFR3 gene is a receptor
  that regulates bone growth by limiting the
  formation of bone from cartilage (a process
  called ossification), particularly in the long
  bones. Researchers believe that mutations in the
  FGFR3 gene cause the receptor to be overly
  active, which interferes with ossification and
  leads to the disturbances in bone growth seen
  with this disorder.

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• There are 4 nucleotide substitutions in
  Achondroplasia.
• It can be inherited but more than 80 of the
  cases are results from a mutation that occurred
  during development.
• Compression of the spinal cord and/or upper
  airway obstruction increases the risk of death in
  infancy.
• Homozygous achondroplasia, caused by the presence
  of two mutant alleles at nucleotide 1138 of the
  FGFR3 gene, is a severe disorder with radiologic
  changes qualitatively different from those of
  achondroplasia. Early death results from
  respiratory insufficiency because of the small
  thoracic cage and neurologic deficit from
  cervicomedullary stenosis

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Clinical Features

• nonproportional dwarfism
• shortening of the proximal limbs (called
  rhizomelic shortening)
• short fingers and toes
• a large head with prominent forehead
• small midface with a flattened nasal bridge
• spinal kyphosis (convex curvature) or lordosis
  (concave curvature)
• varus (bowleg) or valgus (knock knee) deformities
  
• frequently have ear infections (due to Eustachian
  tube blockages), sleep apnea (which can be
  central or obstructive), and hydrocephalus

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Diagnosis The physical features are usually
sufficient for an accurate diagnosis. Radiology,
ultrasound, and other imaging techniques are used
to observe the skeletal abnormalities.

A DNA-based test
is
available for new- borns before the

symptoms appear
in atypical
cases.
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Treatments

• All treatments are supportive.
• In newborns, because of the large head and weak
  neck muscles, positions that could block
  breathing must be avoided.
• Infections of the inner ear in children is
  common.
• Preventative measures must be taken against
  apnea, cessation of breathing during sleep.
• Excessive weight gain must be controlled in
  children.
• Orthopedic surgery to elongate limb bones, growth
  hormone therapy, and psychiatric help are often
  taken to deal with the short stature.

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References

• http//en.wikipedia.org/wiki/Achondroplasia
• http//www.carolguze.com/images/clinical/ACH.jpg
• http//www.geneclinics.org/profiles/achondroplasia
  /details.html
• http//www.genecards.org/cgi-bin/carddisp?FGFR3
• http//ghr.nlm.nih.gov/ghr/disease/achondroplasia
• Pasternak, Jack J. 2nd ed. Hoboken John Wiley
  Son, Inc, 2005. 545-547.