Hereditary Multiple Exostoses (HME) is a rare pediatric disorder caused by loss-of-function mutations in the genes encoding the heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2. HME is characterized by formation of cartilaginous outgrowths—called osteochondromas- next to the growth plates of many axial and appendicular skeletal elements. Surprisingly, it is not known whether such tumors also form in endochondral elements of the craniofacial skeleton. Here, we carried out a retrospective analysis of cervical spine MRI and CT scans from 50 consecutive HME patients that included cranial skeletal images. Interestingly, nearly half of the patients displayed moderate defects or osteochondroma-like outgrowths in the cranial base and specifically in the clivus. In good correlation, osteochondromas developed in the cranial base of mutant Ext1f/f;Col2-CreER or Ext1f/f;Aggrecan-CreER mouse models of HME along the synchondrosis growth plates. Osteochondroma formation was preceded by phenotypic alteration of cells at the chondro-perichondrial boundary and was accompanied by ectopic expression of major cartilage matrix genes -collagen 2 and collagen X- within the growing ectopic masses. Because chondrogenesis requires bone morphogenetic protein (BMP) signaling, we asked whether osteochondroma formation could be blocked by a BMP signaling antagonist. Systemic administration with LDN-193189 effectively inhibited osteochondroma growth in conditional Ext1-mutant mice. In vitro studies with mouse embryo chondrogenic cells clarified the mechanisms of LDN-193189 action that turned out to include decreases in canonical BMP signaling pSMAD1/5/8 effectors but interestingly, concurrent increases in such anti-chondrogenic mechanisms as pERK1/2 and Chordin, Fgf9 and Fgf18 expression. Our study is the first to reveal that the cranial base can be affected in patients with HME and that osteochondroma formation is amenable to therapeutic drug intervention.

Level IV--case series.

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Since the 1950s, valgus-producing femoral osteotomy has been the preferred treatment for significant coxa vara. Despite well-performed surgeries, the literature cites recurrence rates of 30-70%. The present study reviews our past 15 years of surgical experience for coxa vara; 26 children with 37 affected hips were retrospectively evaluated for outcome following valgus osteotomy. Both congenital and acquired types of coxa vara were included. Overall recurrence rate following valgus osteotomy was 50%. Age at time of surgery, type of surgery, and type of implant and etiology were found to have no bearing on recurrence. However, if Hilgenreiner's epiphyseal angle was corrected to < 38 degrees, 95% of children had no recurrence of varus. In contrast, head-shaft angle was found not to be a reliable indicator of appropriate correction. Only six of 37 hips required pelvic osteotomy (five Pemberton, one Chiari) for dysplasia, and four of these had developmental dysplasia of the hip as the underlying etiology for their coxa vara. However, if the proximal femur was corrected and maintained before age 10, 83% of children had excellent acetabular depth, spherical congruency, relief from pain, and correction of Trendelenburg gait at latest follow-up.

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Pediatric patients with PF have low mortality and few complex fractures. The pelvis examination appears to have both high specificity and negative predictive value.