Gene: TRPV4
Protein: transient receptor potential cation channel, subfamily V, member 4
Clinical characteristics:
- Spondylometaphyseal dysplasia, Koslowski type
- Typically diagnosed around 2 years of age
- 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
- Brachyolmia type 2 (spondyloepiphyseal dysplasia, Maroteaux type)
- Parastremmatic dysplasia
Inheritance pattern: Autosomal dominant
What this test can tell us:
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 3 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 one or two 4-cc tubes of blood in EDTA/ purple top tube (minimum of 1-2 cc for infants)
Turn-around time: 10-14 days
CPT codes and cost:
Full Sequencing:
83891(x1) 83900(x1) 83901(x2) 83898(x2) 83904(x28) 83912(x1) $1,400
Partial Sequencing:
83891 (x1) 83898 (x6) 83904 (x12) 83912 (x1) $500
TRPV4-Related Skeletal Dysplasias Testing Packet