Hypochondroplasia is a skeletal dysplasia characterized by short stature; stocky build; disproportionately short arms and legs; broad, short hands and feet; mild joint laxity; and macrocephaly. The skeletal features are very similar to achondroplasia but tend to be milder. Medical complications common to achondroplasia (e.g., spinal stenosis, tibial bowing, obstructive apnea) occur less frequently in hypochondroplasia, but deficits in mental capacity and/or function may be more prevalent. Children usually present as toddlers or school-age children with short stature; limb disproportion and other features become more prominent with time. Individuals with mild achondroplasia and severe hypochondroplasia present similarly.

The majority of cases of hypochondroplasia are due to mutations in the FGFR3 gene. Inheritance is autosomal dominant, although most cases are due to de novo mutations (i.e., both parents are of normal stature). Approximately 70% of probands with hypochondroplasia are heterozygous for the FGFR3 p.Asn540Lys mutation, due to one of two recurrent FGFR3 mutations, c. 1620C>A (in 70%) and c.1620C>G (in 30%). The achondroplasia mutation, p.Glu380Arg (c.1138G>A; c.1138G>C), may present clinically as severe hypochondroplasia . Other rare FGFR3 mutations have been reported.

1. Confirmation of diagnosis:
   1. In individuals with clinical features suggestive of hypochondroplasia.
2. Prenatal testing (technically feasible, but not routinely performed – contact MGL to discuss):
   1. In pregnancies born to a couple in which one or both parents has hypochondroplasia

Bidirectional Sanger sequencing of the regions of FGFR3 encompassing the common hypochondroplasia mutation p.Asn540Lys (c.1620C>A; c.1620C>G), the rare p.Asn540Thr (c.1619A>C), p.Asn540Ser (c.1619A>G), and p.Ile538Val (c.1612A>G) mutations and the achondroplasia mutation p.Glu380Arg (c.1138G>A; c.1138G>C).

NM_000142.4 The ‘A’ within the initiation codon, ATG, is designated as nucleotide number 1.

Blood: 4 mL EDTA is optimal (Minimum: 1 mL EDTA)
DNA: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth and ship to the address below. Samples should be shipped at room temperature with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays).  

Prenatal Specimens
Prenatal testing REQUIRES LABORATORY CONSULTATION PRIOR TO THE PROCEDURE and can only be ordered by a Medical Geneticist. Contact the laboratory at 604-875-2852 and choose the appropriate option for the Molecular Geneticist on service.
Chorionic Villi: 20 mg.
Direct Amniotic fluid: 25 mL collected in two separate tubes of equal volume.
Cultured Amniocytes: Two (2) 100% confluent T-25 flasks.
DNA extracted from prenatal specimens: 100 μL at 200 ng/μL is optimal (Minimum: 30 μL at 200 ng/μL)

Label each sample with three patient identifiers; preferably patient name, PHN, and date of birth. Ship samples by overnight courier with a completed MGL Requisition to arrive Monday to Friday (not on Canadian statutory holidays) as follows:

• Villi – on wet ice or in media at room temperature
• Amniocytes, Amniotic fluid, DNA – at room temperature

Testing is only available to residents of Canada, except in very specific circumstances where testing is urgent or emergent.  Payment is not required when requests are made for individuals who are insured by Health Insurance BC (administered through the BC Medical Services Plan (MSP)) AND eligible for testing according to the test utilization guidelines / policy. If the individual undergoing testing is not insured by these providers or does not meet utilization guidelines or policy, please complete a billing form; testing will only commence after receipt of billing informationTest prices can be found here.

Molecular genetic testing is limited by the current understanding of the genome and the genetics of a particular disease, as well as by the method of detection used.

Rare single nucleotide variants or polymorphisms could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, consult the on-service Molecular Geneticist.

A previous bone marrow transplant from an allogenic donor will result in molecular data that reflects the donor genotype rather than the recipient (patient) genotype. Consult the on-service Molecular Geneticist for approach to testing in such individuals.

Transfusions performed with packed red blood cells will generally not affect the outcome of molecular genetic testing. However, if there is no clinical urgency, the cautious approach is to wait one week post packed red cell transfusion before collecting a sample for genetic testing. Consult the on-service Molecular Geneticist as needed.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.