Recommended first line test to confirm clinical suspicion of a SHOX-related disorder.
Multiplex Ligation-dependent Probe Amplification
Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD).
Transport 3 mL whole blood. (Min: 2 mL)
Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
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.
Laboratory Developed Test (LDT)
|Component Test Code*||Component Chart Name||LOINC|
|3001396||SHOX Disorders DelDup Specimen|
|3001397||SHOX Disorders DelDup Interp|
- Langer mesomelic dysplasia (LMD)
- Leri-Weill dyschondrosteosis (LWD)
- Short stature