Achondroplasia

Clinical Features
• Achondroplasia literally means “without cartilage
formation.”
• Presents clinically as a long narrow trunk with short
extremities, large head with frontal bossing, hypoplasia
of the midface, and trident configuration of the hands.
• An autosomal dominant disorder; a majority of cases are
sporadic, the result of a de novo mutation.
• A de novo mutation is a new mutation that occurs in a
germ cell and is then passed on to an offspring.
 FGFR3 Gene
• The gene affected is the Fibroblast Growth
Factor Receptor 3 gene, of FGFR3.
• FGFR3 is located on chromosome 4, 4p16.3
 Mutation
• There is a G to A transition at nucleotide 1138
of the coding sequence resulting in a gly380 to
arg substitution.
• Glycine is a basic side chain with its positive
charge stabilized by resonance.
• Arginie is a nonpolar side chain consisting of a
single hydrogen atom.
• GGG changes to AGG in the majority of the
cases of achondroplasia.
 Protein Function
• These proteins play a role in several important cellular
processes, including regulation of cell growth and
division, determination of cell type, formation of blood
vessels, wound healing, and embryo development.
• FGFR3 is a transmembrane protein.
• The FGFR3 protein is involved in the development and
maintenance of bone and brain tissue. Researchers
believe that this receptor regulates bone growth by
limiting the formation of bone from cartilage in the long
bones.
 Diagnosis in Humans
• Easier since the phenotype is apparent at birth

• Expected if a parent is diseased

• At least X-ray analysis, at most RFLP – restriction

enzyme SfcI

• May diagnose prenatal embryos

 Treatment
• New method of adding height, called distraction
osteogenesis, is being researched
- Lengthen tibia bone with very few risks
- Increase of 4.0 +/- 1.98 centimeters

• Growth hormone therapy is still under study

• Gene Therapy possibility

• Altered clothing, car-pedal extensions, respect from

average-sized individuals, and even a support group (see
next slide) all help the low self-esteem and depression that
is common