ESPE Abstracts (2019) 92 P3-287

Should Wereviewclinical Criteria to Diagnose SHOX Gene Mutations?

Francesco Gallo, Antonella Lonero, Fulvio Moramarco


Unit of Pediatrics, Brindisi, Italy


The mutation of the SHOX gene is a cause of short stature by varying frequency depending on the published work, but estimated at around 3-10 % of cases of short stature. The main diagnostic scheme for starting genetic testing is the Rappold score, which requires clinical and radiological criteria, under which this form of short stature is framed as a disharmonious. In our clinical experience, however, we also looked for mutations in the SHOX gene in patients with signs of growth hormone deficiency as defined by the Italian legislature with the note of the Italian drug agency AIFA, such as a defiance of stature growth speed, significant short stature or insufficient pubertal growth spurt. In the last ten years, we have assessed 496 boys and girls with the above criteria. We diagnosed GH deficiency in 50 cases and mutations in the SHOX gene in 10 cases, two of which achieved the minimum score predicted by the Rappold scheme. There was always at least one parent with short stature. Growth hormone was given at the dose of 0.035-0.05 mg/kg/die until the final stature (two cases) was reached, always with good stature response and with a final height within the genetic target (see table) . In our opinion, we need to review the criteria for accessing genetic diagnostics for SHOX mutations, performing this survey in all cases that require investigations for suspected GH deficiency.

PtSexAge of diagnosisRappold scoreH SDS at diagnosisBone Age at diagnosisTarget heightcmH SDS at last visitFinal height cmGene anomaly
1M2.042-2,91.5169.6-2microdupl
2M14.92-2,413170,5-2microdupl
3M12.350-1,710.5173.2-1,2microdupl
4F5.72-1,44.5157.6-0,7ENHANCER
5F3.50-0,82.5159.5-0,6del
6M7.70-1,55.5169.8-1,1del
7M12.62-1,711175-0,2174.6microdupl
8F12,84-2,713149,4-2,6147.9del
9M8.74-17.5161.4- 0.9del
10M10.46-1,77,5154-1,2del

1) Rappold G et al: Gentotypes and phenotypes in children with short stature: clinical indicators of SHOX aploinsufficiency. J Med Genet 2007, 44: 306-313.

2) Léger J1. How should we investigate children with growth failure? Ann Endocrinol (Paris). 2017 Jun;78(2):106-107. doi: 10.1016/j.ando.2017.04.008. Epub 2017 Apr 28.

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