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SHOX-Related Disorders, Deletion/Duplication
3001395
Ordering Recommendation

Recommended first line test to confirm clinical suspicion of a SHOX-related disorder.

Mnemonic
SHOX DD
Methodology
Multiplex Ligation-dependent Probe Amplification
Performed
Varies
Reported
12-14 days
New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
ARUP Consult®
Disease Topics
Specimen Required
Patient Preparation
 
Collect
Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD). 
Specimen Preparation
Transport 3 mL whole blood. (Min: 2 mL) 
Storage/Transport Temperature
Refrigerated. 
Unacceptable Conditions
 
Remarks
 
Stability
Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months 
Reference Interval
By Report
Interpretive Data
Background Information for SHOX-Related Disorders, Deletion/Duplication:
Characteristics of SHOX-related disorders (SHOX deficiency): Short stature, mesomelia, and abnormal alignment of the radius, ulna, and carpal bones at wrist (Madelung deformity). Variable expressivity results in some affected individuals with syndromic short stature and additional findings (eg, Leri-Weill dyschondrosteosis (LWD) or Langer mesomelic dysplasia (LMD)), while others have isolated short stature (ISS).
Prevalence of SHOX deficiency: 1 in 1,000
Inheritance: SHOX is located in pseudoautosomal region 1 (PAR1) on the X and Y chromosomes and escapes X inactivation. Thus, inheritance is pseudoautosomal dominant for ISS and LWD, and pseudoautosomal recessive for LMD.
Penetrance: High, with variability in expression.
Cause: One pathogenic variant (haploinsufficiency) of the SHOX gene causes ISS and LWD. Two pathogenic variants in SHOX (complete loss of SHOX) causes LMD.
Clinical Sensitivity: Approximately 80-90 percent of disease-causing SHOX variants are deletions.
Methodology: Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large deletions/duplications in the SHOX gene and surrounding SHOX region, which includes upstream and downstream enhancer elements in the pseudoautosomal 1 region (PAR1).
Analytical Sensitivity and Specificity: Greater than 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Deletion/duplication breakpoints are not determined. Contiguous gene syndromes, complex rearrangements, chromosome translocations, inversions or aneuploidy affecting the sex chromosomes are not detected by this assay; additional testing may be required in such cases. SHOX sequence variants, and deep intronic and promoter variants are not detected.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.

Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Note
Hotline History
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Components
Component Test Code*Component Chart NameLOINC
3001396SHOX Disorders DelDup Specimen
3001397SHOX Disorders DelDup Interp
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • Langer mesomelic dysplasia (LMD)
  • Leri-Weill dyschondrosteosis (LWD)
  • Short stature
  • SHOX