SHOX gene deletion screening by FISH in children with short stature and Madelung deformity and their characteristics

Abstract

AbstractBackgroundThe short stature homeobox-containing (SHOX) gene strongly affects height. Therefore, a better understanding ofSHOXhaploinsufficiency could be advantageous to early diagnosis and treatment. We investigated the rate ofSHOXhaploinsufficiency in patients of short stature and documented their anthropometric measurements.MethodsBetween 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 withoutSHOXhaploinsufficiency as determined by fluorescencein situhybridisation (FISH).ResultsAccording 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 ofSHOX, 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.ConclusionsAs we likely missed cases due to our methodology, the routine analysis forSHOXscreening 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 withSHOXdeficiency are required.