Abstract
Background
The short stature homeobox-containing (SHOX) gene strongly affects height. Therefore, a better understanding of SHOX haploinsufficiency could be advantageous to early diagnosis and treatment. We investigated the rate of SHOX haploinsufficiency in patients of short stature and documented their anthropometric measurements.
Methods
Between 2010 and 2017, we evaluated 86 patients (70 females, 16 males; age 4.3–18 years) with clinical diagnoses of short stature and Madelung deformity (MD). Clinical abnormalities are presented for patients with MD with and without SHOX haploinsufficiency as determined by fluorescence in situ hybridisation (FISH).
Results
According to our inclusion criteria, 78 of 86 patients (70 females, 16 males) had short stature (height <−2.5 standard deviation [SD]) and a family history suggestive of short stature. Eight patients had short stature, a family history suggestive of short stature and MD. MD was obvious in eight children in radiographic examinations. Although five of these had no deletion of SHOX, three had deletion of this gene. The deletion detection rate was 37.5% in the individuals with short stature and MD, i.e. Leri-Weill dyschondrosteosis syndrome (LWS), whilst no deletions were detected in the individuals with only short stature. One individual responded well to growth hormone (GH) treatment for the first 2 years but then developed an intolerance with persistently elevated insulin-like growth factor-1 (IGF-1) levels.
Conclusions
As we likely missed cases due to our methodology, the routine analysis for SHOX screening should be firstly multiplex ligation-dependent probe amplification (MLPA). The incidence of MD may have been higher in the cohort if X-rays were performed in all individuals. GH treatment was not well tolerated in one case due to persistently elevated IGF-1 levels, and long-term evaluations of patients with SHOX deficiency are required.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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