ESPE Abstracts

Background: Gene SHOX haploinsufficiency due to deletions or mutations in heterozygosis causes a wide spectrum of phenotypes ranging from very severe disharmonic short stature (S. Léri-Weil, S. Turner) to very mild forms with the appearance of idiopathic short stature (IST) of difficult clinical recognition. Auxological study directed at evaluating body disproportions such as the sitting height/height (SH/H) ratio in patients with IST has been postulated as useful for orienting the SHOX gene.

Objective and hypotheses: To establish the prevalence of SHOX gene defects in children with disharmonic short stature evaluated by the (SH/H) ratio regardless of the presence of dysmorphic features and radiological anomalies.

Method: Prospective study of 37 consecutive patients with height <−2 S.D. and (SH/H) ratio >+2 S.D.. All initially underwent genetic study using MPLA or CGH array. Sequencing of all exons of the SHOX gene and flanking intronic regions was carried out in patients without SHOX gene deletion or its regulating regions.

Results: The following defects of the SHOX gene were located in eight patients (six girls; age range: 9.9±3.3 years and height: −2.7±0.9 S.D. Complete deletion: 2, complex reorganisation of the regulating region: 2, regulating region deletion: 1, duplication 0.56 Mb: 1, partial deletion: 1 and p.Ala267dup mutation in exon 5: 1. A further three patients were diagnosed of Turner syndrome (kariotypes: 46, X; 46, XX (65%)/45, X; 46, X,+mar).

Conclusion: The frequency of SHOX gene defects in our cohort with disharmonic IST evaluated by the (SH/H) ratio was 29.7%. The (SH/H) ratio is a highly useful parameter for identifying patients with disharmonic IST and orienting SHOX gene study. A significant proportion of patients with disharmonic IST remain undiagnosed, which renders this an open field for clinical research.