Achondroplasia

Question 1

What are the general features of achondroplasia?

Answer 1

Form of dwarfism: short arms and legs with a normal torso size

• Reduced stature (height)
• Characteristic facial features include large head size and flattening of the bridge of the nose
• Shortened fingers
• Trident hand (separation between middle and adjacent fingers)

Question 2

What causes achondroplasia?

Answer 2

A gain of function mutations in the FGFR3 gene leads to achondroplasia

FGFR3 is a receptor tyrosine kinase

Question 3

What is the function of FGFR3?

Answer 3

• FGFR3 is a transmembrane receptor tyrosine kinase
• Ligand binding outside the cell leads to intracellular responses
• Promotion of cartilage differentiation into bone
• G380R mutation of FGFR3 causes unregulated activity
• Growth plate is prematurely converted to bone

Question 4

Aside from achondroplasia, what can mutations in FGFR3 lead to?

Answer 4

Other mutations can occur on FGFR3 to lead to skeletal dysplasia disorders; all are very rare

Question 5

What type of mutation is achondroplasia?

Answer 5

A classic autosomal dominant disorder