Hypochondroplasia

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HYPOCHONDROPLASIA

Gene Symbol: FGFR3

Chromosomal Locus: 4p16.3

Protein: Fibroblast growth factor receptor 3

Pseudonyms: HCH

TURNAROUND TIME: 10 business days

 TESTING METHODOLOGY: Polymerase chain reaction (PCR) and DNA Sequencing of the region of encompassing the most common mutations, including N540K (c. 1620>A/G).

SPECIMEN REQUIREMENTS:

  • Collect: Prefer two 5ml whole blood EDTA (lavender top) tube.
  • Min. Collection: 0.7 ml whole blood EDTA.
  • Transport: blood EDTA at Room Temp shipped regular next day air (No Saturday delivery; store specimen at 4°C and ship Monday)
  • Stability: Ambient: up to 7 days; Refrigerated: 2 weeks. Frozen: unacceptable
  • Unacceptable Conditions: Serum. Frozen or severely hemolyzed blood. Clotted blood.
  • Prenatal testing: Direct: 5ml direct unspun amniotic fluid or 15mg CVS tissue with a backup flask growing. Culture: confluent T25 flask. Maternal blood sample is required for maternal cell contamination studies.

A Molecular Genetics Laboratory Test Requisition must accompany the specimen. Contact the Molecular Laboratory at 918-502-1721 to obtain further information.

Note:
Counseling and informed consent are recommended for genetic testing; Center for Genetic Testing at Saint Francis consent form is available as a resource but not required.

INTERPRETATIVE DATA:

Incidence: unknown; estimated to be 1 in 15,000 to 40,000.
 
Inheritance: may be spontaneous or inherited in an autosomal dominant manner.
 
Disease Characteristics: HCH is a form of dwarfism resulting in 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 (ACH) but usually milder. Children usually present as toddlers with failure to grow. Limb disproportion and other features become more prominent with age.
 
Molecular Genetic Mechanism: A single variant, (N540K) in the Fibroblast Growth Factor Receptor, Type 3 (FGFR3) gene, has been discovered to cause approximately 70% of HCH of both spontaneous and hereditary types.
 
Related Tests: Achondroplasia; Dwarfism Panel. Mild ACH and severe HCH may have similar presentations. Therefore, it is suggested to test for both when DNA testing is requested for dwarfism.
 
Clinical Sensitivity: 99%
 
Analytic Sensitivity: >99%
 
Test Limitations: Deletions of the entire FGFR3 gene or mutations located outside the tested region (roughly 5-10%) are not detected.

INDICATIONS FOR USE:

  • To confirm the nature of the dwarfism in an affected individual.
  • To evaluate fetal development with unusually small stature by ultrasound.
  • Individuals at risk due to family history who wish prenatal diagnosis.

ADDITIONAL RESOURCES:

OMIM Hypochondroplasia: www.omim.org/entry/146000
OMIM FGFR3: www.omim.org/entry/134934
Genetics Home Reference: www.ghr.nlm.nih.gov/condition/hypochondroplasia