Robinow Syndrome and Autosomal Recessive Brachydactyly, Type B1 via the ROR2 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes STAT Prenatal
8359 ROR2$890 8147981479,81479 Add to Order

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Robinow syndrome is characterized by dysmorphic facial features, short stature, genital hypoplasia, shortening of the forearms, and other skeletal abnormalities. All patients exhibit hypertelorism and a small upturned nose. The majority of patients also have frontal bossing, prominent eyes, downslanting palpebral fissures, long philtrum, downturned triangular mouth, micrognathia, and crowded teeth. Mesomelic shortness is another universal finding, and most patients have small hands with clinodactyly. Thumbs and great toes are sometimes broad. Vertebral anomalies distinguish recessive Robinow syndrome (OMIM 268310) resulting from ROR2 variants from the dominant form (see below). Patients with recessive Robinow syndrome often have thoracic hemivertebrae, rib anomalies, and scoliosis, while patients with the dominant form do not (von Bokhoven et al. Nature Genet 25:423-426, 2000). Brachydactyly occurs as part of many syndromes or as an isolated finding. ROR2-associated type B brachydactyly (OMIM 113000) can be distinguished from other nonsyndromic forms by shortening and hypoplasia of the distal phalanges, dysplasia or aplasia of the nails, and hypoplasia of the middle phalanges (Schwabe et al. Am J Hum Genet 67:822-831, 2000). Other distinguishing features are biphalangeal digits, syndactyly, and bilateral symmetry of the abnormalities (Oldridge et al. Nature Genet 24:275-278, 2000).

Genetics

Both autosomal recessive and dominant forms of Robinow syndrome are known. Recessive Robinow syndrome is associated with loss of function variants in ROR2 (Ali et al. Nat Genet 25:419-422, 2000), many of which result in defective intracellular trafficking (Ali et al. Hum Genet 122:389-395, 2007). The ROR2 gene (OMIM 602337) encodes a cell surface receptor tyrosine kinase involved in development of the skeletal, cardiovascular, and genital systems. The etiology of dominant Robinow syndrome, which is clinically milder and probably the rarer form, is unknown. Type B1 brachydactyly is inherited as an autosomal dominant condition. Variants that lead to truncation of the intracellular part of the protein after the tyrosine kinase domain cause dominant brachydactyly via a gain of function mechanism (Oldridge et al. 2000; Schwabe et al. 2000).

Testing Strategy

This test provides full coverage of all coding exons of the ROR2 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV

Clinical sensitivity should be high for Robinow syndrome when patients meet strict phenotypic criteria and evidence exists for recessive inheritance. Analytic sensitivity may be limited due to the presence of intragenic deletions (Brunetti-Pierri et al. Am J Med Genet 146A:2804-2809, 2008). Clinical and analytical sensitivity for type B1 brachydactyly should be high in cases with characteristic findings of the phalanges.

Indications for Test

Individuals with clinical findings consistent with Robinow syndrome and recessive inheritance or nonsyndromic brachydactyly with dominant inheritance. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ROR2.

Gene

Official Gene Symbol OMIM ID
ROR2 602337
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Symphalangism, Proximal, Multiple Synostoses Syndrome, Stapes Ankylosis with Broad Thumb and Toes, Tarsal-Carpal Coalition Syndrome, and Brachydactyly, Type B2 via the NOG Gene

Citations

  • Ali, B. R., et.al. (2007). "Novel Robinow syndrome causing mutations in the proximal region of the frizzled-like domain of ROR2 are retained in the endoplasmic reticulum." Hum Genet 122(3-4): 389-95. PubMed ID: 17665217
  • Brunetti-Pierri, N., et.al. (2008). "Robinow syndrome: phenotypic variability in a family with a novel intragenic ROR2 mutation." Am J Med Genet A 146A(21): 2804-9. PubMed ID: 18831060
  • Oldridge, M., et.al. (2000). "Dominant mutations in ROR2, encoding an orphan receptor tyrosine kinase, cause brachydactyly type B." Nat Genet 24(3): 275-8. PubMed ID: 10700182
  • Schwabe, G. C., et.al. (2000). "Distinct mutations in the receptor tyrosine kinase gene ROR2 cause brachydactyly type B." Am J Hum Genet 67(4): 822-31. PubMed ID: 10986040
  • van Bokhoven, H., et.al. (2000). "Mutation of the gene encoding the ROR2 tyrosine kinase causes autosomal recessive Robinow syndrome." Nat Genet 25(4): 423-6. PubMed ID: 10932187

Ordering/Specimens

Ordering Options

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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