Radiological features in patients with SHOX deficiency - Comparison between idiopathic short stature (ISS) and Léri-Weill dyschondrosteosis (LWD) Radiological features in patients with SHOX deficiency - Comparison between idiopathic short stature (ISS) and Léri-Weill dyschondrosteosis (LWD) SHOX Gabriel Kalifa 1, Werner F. Blum 2, Solène Ferey 1, Brenda J. Crowe 3, Elena P. Shavrikova 4, Christine Jones 2, Beate Niesler 5, Gudrun Rappold 5 1 Department of Radiology, Saint Vincent de Paul Hospital, Paris, France; 2 Eli Lilly and Company, Bad Homburg, Germany; 3 Eli Lilly and Company, Indianapolis, USA; 4 Pharma Support Inc., St. Petersburg, Russia; 5 Department of Molecular Human Genetics, University of Heidelberg, Heidelberg, Germany INTRODUCTION Haploinsufficiency of the SHOX gene causes short stature with clinical and radiological phenotypes varying from ISS to LWD. The aim of this study was to identify specific radiological features in patients with SHOX deficiency and to compare their frequencies in ISS and LWD phenotypes. PATIENTS Short prepubertal children from 12 countries with age  3 y and height <3 rd %ile (N=50; 26 females) were enrolled. SHOX defects were confirmed using FISH or intragenic polymorphism analysis to detect deletions, or by denaturing HPLC (WAVE  ) and DNA sequencing to detect point mutations. A complete SHOX deletion was present in 32, a partial deletion in 4, and a point mutation in 14 patients. Of the 50 patients, 24 were clinically diagnosed with ISS and 26 with LWD. Baseline characteristics were as follows (mean  SD): age: 7.3  2.4 y ; bone age SDS (Greulich-Pyle):  1.20; height SDS:  0.90, with no significant differences between the ISS and LWD groups. RADIOLOGICAL ASSESSMENT X-ray images (hand/wrist, forearm in two dimensions and lower leg) were read by a single investigator who did not know the clinical diagnosis (GK).  Bone age  Bone transparency  Bone shape (especially distal radial epiphysis, metacarpals)  Forearm bones curvature and length  Elbow and wrist aspect  Femoral condyles  Tibial and fibular shape and length RESULTS ISS Normal hand, normal metacarpal length. No modification of the distal radial epiphysis. Normal aspect of the wrist. Mild osteoporosis. The distal radial epiphysis is convex as well as the growth cartilage. No other abnormality. Table 2. Radiological abnormalities in ISS vs LWD Prominent internal femural condyle Tibial tuberosities Bowing of tibia Elbow deformities Bowing of ulna Bowing of radius th Metacarpals short th Metacarpals short %N%N P LWDISS Variable RESULTS cont’d LWD Abnormal hand wrist wedging. Obvious slope of the distal radial epiphysis with evidence of radial bowing. These findings are highly suggestive of dyschondrosteosis. Mild tibial bowing with prominent tibial internal tuberosity. Enlarged internal femoral condyle. Two examples of more severe Madelung deformity with abnormal orientation of the distal portion of the radius, convex shape of the radial epiphysis. On the right side the deformity is associated with shortening and may suggest a more severe form of dyschondrosteosis, resembling mesomelic dysplasia. Very mild radial bowing. Normal ulnar aspect. No shortening of the forearm. Normal aspect of the lower leg: The femoral condyle is normal as is the tibial plateau. Normal alignment of the bones without any bowing. Table 1. Degrees of radiological abnormalities in ISS vs LWD and comparison of percentages Round shaped Severe 2623N Severe Convex Triangular < Normal Distal radial epiphysis Moderate Mild Normal Radial lucency Moderate Mild Normal Hand/wrist carpal wedging PLWDISSDegreeVariable CONCLUSIONS  Radiological anomalies are present in an unexpectedly high proportion of patients with SHOX deficiency clinically diagnosed with ISS.  The frequencies of a number of radiological signs are not different between “ISS” and LWD, despite the different clinical phenotypes.  X-rays of the forearm and lower leg can provide important indicators of SHOX deficiency and should therefore be mandatory in the diagnostic work-up. The distal radial epiphysis deserves special attention. Funded by Eli Lilly and Company meeting ; location ; date