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.
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 Category

Laboratory Developed Test (LDT)

Note
Hotline History
N/A
CPT Codes

81479

Components
Component Test Code* Component Chart Name LOINC
3001396 SHOX Disorders DelDup Specimen
3001397 SHOX 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
SHOX-Related Disorders, Deletion/Duplication