TRPV4-Related Skeletal Dysplasias

Gene: TRPV4

Protein: transient receptor potential cation channel, subfamily V, member 4

Clinical Characteristics

Spondylometaphyseal Dysplasia, Koslowski Type

  • Typically diagnosed around age 2
  • Short stature of postnatal onset
  • Progressive kyphoscoliosis
  • Waddling gait
  • Radiographic findings:
    • Odontoid hypoplasia
    • Delayed bone age
    • Platyspondyly and widely spaced vertebral pedicles
    • Metaphyseal irregularities
    • Short square ilia, flat acetabular roofs, wide proximal femoral epiphyses

Metatropic Dysplasia

  • Short limbs and long narrow trunk in newborn period
  • Joint contractures and enlargement
  • Progressive kyphoscoliosis resulting in short trunk and relatively longer limbs
  • Platyspondyly
  • Metaphyseal enlargement

Brachyolmia Type 3

  • Short trunk
  • Mild short stature
  • Severe kyphoscoliosis
  • Flattened, irregular cervical vertebrae
  • Metaphyseal and epiphyseal abnormalities may be minimal

Recent evidence that TRPV4 mutations also cause:

  • Spondyloepiphyseal dysplasia, Maroteaux type/Brachyolmia type 2
  • Parastremmatic dysplasia

Inheritance pattern: Autosomal dominant

What Can Be Learned From This Test

Testing is performed by sequencing the entire coding region of TRPV4. This will detect point mutations, small deletions and small insertions. It will not detect a partial or whole gene deletion or duplication.

Partial sequencing in regions known to carry mutations can be carried out; please note on submission form if this tiered approach is being requested.

TRPV4 is the only gene known to be associated with these specific disorders. There are other types of spondylometaphyseal dysplasia and brachyolmia that are not associated with mutations in TRPV4. A negative test does not rule out a genetic cause of a skeletal dysplasia, as there are many other genes associated with different types of skeletal dysplasias.

Certain mutations in TRPV4 have been associated with three specific types of autosomal dominant neuromuscular disorders. One of these mutations may be identified during this test. This will be reported to the ordering provider.

Sample Requirements

Draw 2ml–4ml of blood in EDTA/purple-top tube (minimum of 1ml–2ml for infants).

Turnaround time: 10-14 business days

CPT Codes and Cost

Full Gene Sequencing

  • Code: 81479
  • Cost: $1,450

Known Variant Testing

  • Code: 81479
  • Cost: $225

Additional Information