Radiological features in patients with SHOX deficiency Comparison

Radiological features in patients with SHOX deficiency - Comparison between idiopathic short stature (ISS) and Léri-Weill dyschondrosteosis (LWD) Gabriel 1 Kalifa , Werner F. 2 Blum , Solène 1 Ferey , Brenda J. 3 Crowe , Elena P. 4 Shavrikova , Christine 2 Jones , Beate 5 Niesler , Gudrun SHOX 5 Rappold 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, Germany INTRODUCTION RESULTS cont’d RESULTS LWD ISS 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. 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. Abnormal hand wrist wedging. Obvious slope of the distal radial epiphysis with evidence of radial bowing. These findings are highly suggestive of dyschondrosteosis. Normal hand, normal metacarpal length. No modification of the distal radial epiphysis. Normal aspect of the wrist. 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. Mild osteoporosis. The distal radial epiphysis is convex as well as the growth cartilage. No other abnormality. Very mild radial bowing. Normal ulnar aspect. No shortening of the forearm. Mild tibial bowing with prominent tibial internal tuberosity. Enlarged internal femoral condyle. Normal aspect of the lower leg: The femoral condyle is normal as is the tibial plateau. Normal alignment of the bones without any bowing. Baseline characteristics were as follows (mean SD): age: 7. 3 2. 4 y ; bone age SDS (Greulich-Pyle): -0. 93 1. 20; height SDS: 3. 23 0. 90, with no significant differences between the ISS and LWD groups. Table 2. Radiological abnormalities in ISS vs LWD. RADIOLOGICAL ASSESSMENT Variable X-ray images (hand/wrist, forearm in two dimensions and lower leg) th Metacarpals short 4 were read by a single investigator who did not know the clinical diagnosis (GK). ØBone age ØBone transparency ØBone shape (especially distal radial epiphysis, metacarpals) ØForearm bones curvature and length ØElbow and wrist aspect ØFemoral condyles ØTibial and fibular shape and length 5 th Metacarpals short LWD N % 24 20. 8 26 15. 4 24 12. 5 26 11. 5 P 0. 999 34. 8 26 80. 8 0. 001 Bowing of ulna 23 4. 3 26 26. 9 0. 052 Elbow deformities 23 8. 7 26 26. 9 0. 145 Bowing of tibia 22 9. 1 25 12. 0 0. 999 Prominent internal femural condyle 22 13. 6 86. 4 25 25 12. 0 92. 0 Degree ISS LWD 23 26 56. 5 30. 8 13. 0 23. 8 21. 7 34. 6 Severe 8. 7 11. 5 Normal 30. 4 23. 1 Mild 47. 8 34. 6 Moderate 17. 4 38. 5 Severe 4. 3 3. 8 Normal 78. 3 19. 2 0 26. 9 Convex 17. 4 46. 2 Round shaped 4. 3 7. 7 Normal 0. 721 23 22 Variable N Bowing of radius Tibial tuberosities Funded by Eli Lilly and Company meeting ; location ; date ISS Table 1. Degrees of radiological abnormalities in ISS vs LWD and comparison of percentages. 0. 999 0. 654 Hand/wrist carpal Mild wedging Moderate Radial lucency Distal radial epiphysis Triangular P 0. 339 0. 432 <0. 001 CONCLUSIONS ØRadiological anomalies are present in an unexpectedly high proportion of patients with SHOX deficiency clinically diagnosed with ISS. ØThe frequencies of a number of radiological signs are not different between “ISS” and LWD, despite the different clinical phenotypes. ØX-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.