ACHONDROPLASIA/HYPOCHONDROPLASIA 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& mental capacity may be more common. part=achondroplasia or HCH: http://www.ncbi.nlm.nih.gov/ bookshelf/br.fcgi?book=gene GENETICS TEST METHODS &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 chromosome 4 (4p16.3). Both conditions Disorder FGFR3 Gene Mutation www.cagc-accg.ca or the National Society of Genetic occur as a result of different changes in the c.1138G>A (p.Gly380Arg) Counsellors website at FGFR3 gene. ACH c.1138G>C (p.Gly380Arg) www.nsgc.org 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 TEST SENSITIVITY may not detect all possible child. The severity of the disorder in these The mutations indicated above mutations for this disease. A children will vary, depending on the type account for more than 99% of those negative test does not rule out and number of mutations inherited. the possibility of ACH or HCH. present in individuals affected with Achondroplasia, and 70% of those WHO SHOULD BE TESTED? 2. Test results should be 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 .