Improving clinical diagnosis in SHOX deficiency: the importance of growth velocity

Area of Science:

• Pediatrics
• Genetics
• Endocrinology

Background:

• Short stature is a common concern in pediatric endocrinology.
• Short stature homeobox containing gene (SHOX) deficiency (SHOXD) is a genetic cause of short stature.
• Accurate diagnosis of SHOXD is crucial for timely intervention.

Purpose of the Study:

• To determine the prevalence of SHOXD in a cohort of short-statured children.
• To analyze the clinical phenotype and dysmorphic features associated with SHOXD.
• To evaluate the effectiveness of clinical scores and growth velocity in screening for SHOXD.

Main Methods:

• Genetic screening for SHOXD using direct sequencing and multiplex ligation probe-dependent amplification in 281 short-statured children.
• Comparison of clinical characteristics between children with and without SHOXD (n=117).
• Receiver operating characteristic (ROC) curve analysis to determine the optimal cutoff for growth velocity as a screening tool.

Main Results:

• The prevalence of SHOXD was found to be 6.8% in the studied population.
• Children with SHOXD exhibited significantly lower growth velocity (P<0.05) and a higher incidence of dysmorphic signs.
• A growth velocity cutoff of -1.5 standard deviation score (SDS) demonstrated optimal sensitivity and specificity for detecting SHOXD.

Conclusions:

• A growth rate of ≤-1.5 SDS is a valuable indicator for identifying children with SHOXD, irrespective of other clinical signs.
• Utilizing growth velocity or clinical scores like the Rappold score can enhance the sensitivity of genetic testing for SHOXD.
• These findings support the use of specific clinical parameters to guide genetic testing for SHOXD in short-statured children.