Ordering Recommendation

Most comprehensive molecular genetic test to confirm clinical suspicion of a SHOX-related disorder.




Multiplex Ligation-dependent Probe Amplification/Polymerase Chain Reaction/Sequencing




14-28 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

Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD).

Specimen Preparation

Transport 3 mL whole blood. (Min: 2 mL)

Storage/Transport Temperature


Unacceptable Conditions

Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months

Reference Interval

By Report

Interpretive Data

Background information for SHOX-Related Disorders, Deletion/Duplication with Reflex to Sequencing:
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) cause LMD.
Clinical Sensitivity: Approximately 80-90 percent of disease-causing SHOX variants are deletions and 10-20 percent are sequence variants.
Methodology for deletion/duplication analysis: 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).
Methodology for sequencing: Bidirectional Sanger sequencing of the SHOX coding regions, including exons 6a and 6b, and intron-exon boundaries.
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. Repeat element insertions, deep intronic variants and some regulatory region variants are not detected.

This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.

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

Compliance Category

Laboratory Developed Test (LDT)


Deletion/Duplication analysis is performed on all samples. If no large deletions or duplications are detected and/or results do not explain the clinical scenario, then sequencing of the SHOX gene will be added. Additional charges apply. If reflexed, an additional 14 days is required to complete testing.

Hotline History


CPT Codes

81479; if reflexed, add 81405


Component Test Code* Component Chart Name LOINC
3001402 SHOX Reflex Specimen 66746-9
3001403 SHOX DelDup MLPA 41057-1
3001404 SHOX Reflex Interp 34500-9
* 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.


  • Langer mesomelic dysplasia (LMD)
  • Leri-Weill dyschondrosteosis (LWD)
  • Short stature
  • SHOX
SHOX-Related Disorders, Deletion/Duplication with Reflex to Sequencing