G. Kalifa

GH Treatment to Final Height Produces Similar Height Gains in Patients With SHOX Deficiency and Turner Syndrome: Results of a Multicenter Trial

CONTEXT Growth impairment in short stature homeobox-containing gene (SHOX) deficiency and Turner syndrome share a similar etiology. Because of the established effect of GH treatment on height in patients with Turner syndrome, we hypothesized that GH therapy would also stimulate growth in patients with SHOX deficiency. OBJECTIVE Our objectives were to evaluate long-term efficacy of GH treatment in short patients with SHOX deficiency and to compare the effect on final (adult) height (FH) in patients with SHOX deficiency and Turner syndrome. DESIGN AND SETTING A prospective, multinational, open-label, randomized 3-arm study consisting of a 2-year control period and a subsequent extension period to FH. The treatment groups were 1) SHOX-D-C/GH (untreated during the control period, GH-treated during the extension), 2) SHOX-D-GH/GH, and 3) Turner-GH/GH (GH-treated during both study periods). PATIENTS Short-statured prepubertal patients with genetically confirmed SHOX deficiency (n = 49) or Turner syndrome (n = 24) who participated in the extension. INTERVENTION Depending on the study arm, patients received a daily sc injection of 0.05 mg/kg recombinant human GH from start of the study or start of the extension until attainment of FH or study closure. RESULTS Height SD score gain from start of GH treatment to FH was similar between the combined SHOX-deficient groups (n = 28, 1.34 ± 0.18 [least-squares mean ± SE]) and the Turner group (n = 19, 1.32 ± 0.22). In this FH population, 57% of the patients with SHOX deficiency and 32% of the patients with Turner syndrome achieved a FH greater than -2 SD score. CONCLUSIONS GH treatment in short children with SHOX deficiency showed similar long-term efficacy as seen in girls with Turner syndrome.

EOS: A NEW IMAGING SYSTEM WITH LOW DOSE RADIATION IN STANDING POSITION FOR SPINE AND BONE & JOINT DISORDERS

Very precise combined work between multidisciplinary partners (radiation engineers in physics, engineers in biomechanics, medical radiologists and orthopedic pediatric surgeons) has led to the concept and development of a new low-dose radiation device named EOS. This device has three main advantages: (1) Thanks to the invention of Georges Charpak who designed gaseous detectors for X-rays, the reduction of dose necessary to obtain a good image of skeletal system was 8 to 10 times less for 2D imaging; compared to the dose necessary to obtain a 3D reconstruction from CT scan cuts, the reduction factor was 800 to 1000. (2) The accuracy of 3D reconstruction obtained is better than that of 3D reconstruction from CT scan cuts. (3) The patient in addition gets imaged in a standing functional position, thanks to the AP and lateral X-rays obtained from head to feet simultaneously. This is a big advantage compared to CT scans which are used only in lying position. From the simultaneous AP and lateral X-rays of the whole body obtained via the 3D bone external envelop technique, the biomechanics engineers obtain 3D reconstruction of every level of osteo-articular system, especially for spine, in standing position with an acceptable period of time for reconstruction. This (in spite of the evolution of standing MRI) allows more precise bone reconstruction in orthopedics, especially at the level of the entire skeleton, including the head, spine, pelvis, lower limbs, giving new consideration for physiology, physiopathology and therapeutics.

Modélisation vertébrale et squelettique par le système EOS

La durée du balayage est de l’ordre de 15 s pour un adulte et bien sûr décroît avec la taille de l’individu. L’immobilité requise pendant la durée du balayage est cependant une certaine limitation chez les tout jeunes enfants dont certains ne réalisent pas cette immobilité. Des systèmes de contention souple sont à l’étude pour palier à cet inconvénient. Les clichés obtenus sont numériques, non distordus (puisque le rayon est toujours perpendiculaire à l’objet). Ils peuvent être traités numériquement pour avoir un effet zoom sur une articulation précise par exemple. Facilement stockés informatiquement dans l’ordinateur, ils peuvent être délivrés sur fi lm et traités selon la pénétration (zones peu visibles en radio conventionnelle) cela évite la répétition des clichés. Par ailleurs grâce aux logiciels de reconstruction tridimensionnelle mis au point à l’ENSAM en collaboration avec LIO Montréal, une reconstruction 3D surfacique semi automatique de toutes les pièces squelettiques peut être effectuée. La validité de ces reconstructions 3D a été évaluée par rapport à celle obtenue par les coupes jointives obtenues au scanner et vérifi ée tout à fait comparable. Tout cela s’obtient à partir de la seule paire de clichés initiaux avec l’avantage donc d’une diminution considérable des doses d’irradiation (de l’ordre de 800 à 1000 fois moins que les reconstructions 3D scanner). Si l’on se souvient que les dangers de l’irradiation sont d’autant plus importants que l’enfant est jeune, on comprend l’intérêt d’un tel appareil en pédiatrie. Enfi n comme l’examen se fait en position debout, l’infl uence de la gravité est donc bien exprimée grâce à EOS. Le corollaire est un inconvénient : EOS en position couchée n’existe pas encore ce qui l’exclut pour les examens faits obligatoirement en position couchée (traumatismes par exemple).

Radiological Features in Patients with Short Stature Homeobox-Containing (SHOX) Gene Deficiency and Turner Syndrome before and after 2 Years of GH Treatment

Background/Aims: The short stature homeobox-containing (SHOX) gene is one of many genes that regulate longitudinal growth. The SHOX deficiency (SHOX-D) phenotype, caused by intragenic or regulatory region defects, ranges from normal stature to mesomelic skeletal dysplasia. We investigated differences in radiological anomalies between patients with SHOX-D and Turner syndrome (TS) and the effect of 2 years of growth hormone (GH) treatment on these anomalies. Methods: Left hand/wrist, forearm and lower leg radiographs were assessed at baseline and after 2 years in children with genetically confirmed SHOX-D (GH-treated and untreated groups) and TS (GH-treated) in a randomised, controlled, multinational study. Results: Radiological anomalies of hand, wrist and forearm were common in SHOX-D and TS. Radial bowing appeared more prevalent in SHOX-D, while lower leg anomalies were more common in TS. There were no significant differences in radiological findings between GH-treated and untreated patients with SHOX-D after 2 years. Conclusion: GH treatment had no systematic effect on skeletal findings in SHOX-D, based on limited radiological differences between the GH-treated and untreated groups at 2 years. Bone age radiographs allow assessment of radiological signs indicating a potential diagnosis of SHOX-D and may lead to earlier genetic confirmation and initiation of GH therapy.

Apport de l'échographie de hanche dans les boiteries de l'enfant

Resume Objectif Evaluer l’apport de l’echographie de hanche dans la prise en charge d’une boiterie non traumatique de l’enfant. Patients et methodes Etude prospective incluant les enfants consultant pour une boiterie non traumatique (n = 93). Ces enfants ont beneficie d’un examen clinique, d’un bilan biologique et d’imagerie (radiographies du bassin (n = 88), echographie de hanche initiale (n = 93) et de controle (n = 29). Resultats 93 enfants (69 garcons, 24 filles) âges de 10 mois a 13 ans (mediane = 4 ans) ont ete inclus et divises en 2 groupes : • « Echographie positive », n = 39 (42%) avec epanchement articulaire. Tous les enfants presentaient une limitation de la hanche et des radiographies normales. Le diagnostic retenu a ete arthrite septique dans 4 cas, rhume de hanche dans 31 cas et 4 diagnostics particuliers. • « Echographie negative », n = 54 (58 %). 3 patients presentaient des anomalies radiologiques. Chez 12 enfants, un complement d’imagerie a ete necessaire. Aucun epanchement n’est apparu. • La sensibilite et la specificite de l’echographie pour etablir un diagnostic grave etaient respectivement de 57 et 59%. Conclusion L’interet de l’echographie de hanche systematique est remis en cause dans cette etude en raison de ses faibles sensibilite et specificite. Son principal interet semble etre sa negativite, poussant a d’autres investigations.