Aucun titre de diapositive

1
Radiological features in patients with SHOX
deficiency - Comparison between idiopathic short
stature (ISS) and Léri-Weill dyschondrosteosis
(LWD)
SHOX
Gabriel Kalifa1, Werner F. Blum2, Solène Ferey1,
Brenda J. Crowe3, Elena P. Shavrikova4, Christine
Jones2, Beate Niesler5, Gudrun Rappold5 1Departme
nt of Radiology, Saint Vincent de Paul Hospital,
Paris, France 2Eli Lilly and Company, Bad
Homburg, Germany 3Eli Lilly and Company,
Indianapolis, USA 4Pharma Support Inc., St.
Petersburg, Russia 5Department of Molecular
Human Genetics, University of Heidelberg,
Heidelberg, Germany
RESULTS contd
RESULTS
INTRODUCTION
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 lt3rd ile (N50 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) -0.93
?1.20 height SDS -3.23?0.90, with no
significant differences between the ISS and LWD
groups.
Very mild radial bowing. Normal ulnar aspect. No
shortening of the forearm.
Mild osteoporosis. The distal radial epiphysis is
convex as well as the growth cartilage. No other
abnormality.
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.
Table 2. Radiological abnormalities in ISS vs
LWD.
Table 1. Degrees of radiological abnormalities in
ISS vs LWD and comparison of percentages.
CONCLUSIONS
RADIOLOGICAL ASSESSMENT

• 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.

• 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

Funded by Eli Lilly and Company meeting
location date