A CHONDROPLASIA /H YPOCHONDROPLASIA
Achondroplasia (ACH) is characterized by abnormal bone growth that results in For More Information
short stature with disproportionately short arms and legs, a large head, and
characteristic facial features. Intelligence and life span are usually unaffected, Online Mendelian Inheritance in
Man http://www.ncbi.nlm.nih.
although compression of the spinal cord and/or upper airway obstruction during gov/omim/ ACH Item # 100800,
infancy may result in medical complications. HCH Item # 146000
Hypochondroplasia (HCH) is also characterized by short stature with GeneReviews online clinical
disproportionately short arms and legs. The skeletal features are very similar to information resource - ACH:
Achondroplasia but usually tend to be milder. Medical problems common to http://www.ncbi.nlm.nih.gov/
Achondroplasia occur less frequently in Hypochondroplasia, however deficits in bookshelf/br.fcgi?book=gene&
part=achondroplasia or HCH:
mental capacity may be more common.
http://www.ncbi.nlm.nih.gov/
bookshelf/br.fcgi?book=gene
G ENETICS T EST M ETHODS &part=hypochondroplasia
Achondroplasia and Hypochondroplasia are ● Direct mutation detection assay To locate a genetics center near
autosomal dominant disorders caused by using PCR to test for the following you, please visit the Canadian
mutations in the fibroblast growth factor mutations in the FGFR3 gene: Association of Genetic
receptor 3 (FGFR3) gene located on Counsellors website at
Disorder FGFR3 Gene Mutation www.cagc-accg.ca or the
chromosome 4 (4p16.3). Both conditions
National Society of Genetic
occur as a result of different changes in the c.1138G>A (p.Gly380Arg)
Counsellors website at
FGFR3 gene. www.nsgc.org
ACH c.1138G>C (p.Gly380Arg)
Most cases of ACH or HCH are a result of a c.1123G>T (p.Gly375Cys)
new mutation, as the parents are not
c.1620C>A (p.Asn540Lys)
affected and have average stature. In these
cases the risk of having another affected c.1620C>G (p.Asn540Lys)
HCH
child is low. A person with ACH or HCH c.1619A>C (p.Asn540Thr)
whose partner is average-sized has a 50%
chance of having a child with the same c.1612A>G (p.Ile538Val)
condition. When both parents are affected, 1. Current molecular testing
there is a 75% chance of having an affected T EST S ENSITIVITY may not detect all possible
child. The severity of the disorder in these mutations for this disease. A
The mutations indicated above
children will vary, depending on the type negative test does not rule out
account for more than 99% of those
and number of mutations inherited. the possibility of ACH or HCH.
present in individuals affected with
Achondroplasia, and 70% of those 2. Test results should be
W HO S HOULD BE T ESTED ? present in individuals affected with interpreted in the context of
● Individuals clinically suspected of being Hypochondroplasia. A small fraction clinical findings, family history
affected with ACH or HCH of people with ACH and ~30% of and other laboratory data.
● Pregnancies at high risk due to abnormal people with HCH have different
ultrasound findings or a family history of mutations in the FGFR3 gene that 3. Other mutation combinations
ACH or HCH are not detected by this test. are possible in addition to those
listed. These combinations are
very rare and usually result in a
Potential Outcomes & Interpretation of Test Results more serious phenotype.
4. This test was developed and
FGFR3 Gene Mutation Explanation
its performance characteristics
validated by the Genome
None detected This result does not support a diagnosis of Diagnostics Laboratory at the
Achondroplasia or Hypochondroplasia Hospital for Sick Children. It
has not been cleared or
Mutation detected This result supports a diagnosis approved by the U.S. Food and
(Gly380Arg or Gly375Cys) of Achondroplasia Drug Administration. The FDA
has determined that such
Mutation detected (Asn540Thr, This result supports a diagnosis clearance or approval is not
Asn540Lys or Ile538Val) of Hypochondroplasia necessary. This test is used for
clinical purposes.
OMG1620B/02
