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There is a high rate of lower limb deformity and limb length discrepancy in patients with hereditary multiple exostoses (HME). The aim of this study was to evaluate the type and frequency of lower limbs axial deviation and limb length discrepancy and the type of exostoses being risk factors for theses deformities. We retrospectively reviewed standing full-length radiograph of 32 HME patients (64 limbs) followed in our institution between October 2009 and December 2020. Patient demographics were recorded. Radiographic analysis of the coronal limb alignment was performed, limb length discrepancy was measured and topography of the exostoses was recorded. We propose a classification of lower legs in 2 groups and 4 types according to the presence and the location of exostoses. In group I, there is an intertibio- fibular exostose with fibular origin at the level of the tibiofibular joints. In type IA, at the level of the distal tibiofibular joint with ascension of the distal fibula; in type IB at the level of the proximal tibiofibular joint with a bracketing effect on the proximal tibia and a lateral slope of the proximal tibial growth plate; the type IC is combining features of both IA and IB. In group II, there is no intertibio-fibular exostose coming from the fibula and no growth abnormality is obvious. A clinically notable lower limb discrepancy (LLD) of ≥2 cm was found in 19% of our patients. Approximately 33% of patients had a knee valgus deformity and 44% had an ankle valgus deformity. The knee valgus deformity was due to fibular growth anomalies and not to distal femur anomalies. The majority of lower legs had fibular growth anomalies (72%) which was a significant risk factor for knee valgus deformity and leg length discrepancy. On the contrary, we found no correlation between number, location and volume of distal femoral exostoses and genu valgum nor leg length discrepancy. Presence of intertibio-fibular exostoses is a risk factor for knee valgus deformity and le

Metachondromatosis (MC) is a rare, autosomal dominant, incompletely penetrant combined exostosis and enchondromatosis tumor syndrome. MC is clinically distinct from other multiple exostosis or multiple enchondromatosis syndromes and is unlinked to EXT1 and EXT2, the genes responsible for autosomal dominant multiple osteochondromas (MO). To identify a gene for MC, we performed linkage analysis with high-density SNP arrays in a single family, used a targeted array to capture exons and promoter sequences from the linked interval in 16 participants from 11 MC families, and sequenced the captured DNA using high-throughput parallel sequencing technologies. DNA capture and parallel sequencing identified heterozygous putative loss-of-function mutations in PTPN11 in 4 of the 11 families. Sanger sequence analysis of PTPN11 coding regions in a total of 17 MC families identified mutations in 10 of them (5 frameshift, 2 nonsense, and 3 splice-site mutations). Copy number analysis of sequencing reads from a second targeted capture that included the entire PTPN11 gene identified an additional family with a 15 kb deletion spanning exon 7 of PTPN11. Microdissected MC lesions from two patients with PTPN11 mutations demonstrated loss-of-heterozygosity for the wild-type allele. We next sequenced PTPN11 in DNA samples from 54 patients with the multiple enchondromatosis disorders Ollier disease or Maffucci syndrome, but found no coding sequence PTPN11 mutations. We conclude that heterozygous loss-of-function mutations in PTPN11 are a frequent cause of MC, that lesions in patients with MC appear to arise following a "second hit," that MC may be locus heterogeneous since 1 familial and 5 sporadically occurring cases lacked obvious disease-causing PTPN11 mutations, and that PTPN11 mutations are not a common cause of Ollier disease or Maffucci syndrome.

Ultrasonography (US) enables accurate assessment of the cartilage cap of exostoses. The cartilage cap appears as a hypoechoic layer covering the hyperechoic surface of the calcified part. Measurements of cap thickness with US were compared with measurements performed on pathological specimens in 22 resected exostoses and 2 exostotic chondrosarcomas. The US measurements proved to be very accurate, with a mean measurement error of less than 2 mm for cartilage caps less than 2 cm thick. The detection rate and measurement accuracy of US were higher than with computed tomography (CT) and comparable to magnetic resonance imaging (MRI), which were available in 14 and 10 cases, respectively. US appears to be a good procedure for evaluating the cartilage cap, which is usually thin for a benign exostosis and thick for a malignancy. In addition, other complications--such as bursa formation--are easily recognizable. The sole limitation is that US cannot visualize the cartilage cap when it is inwardly orientated or deeply located in soft tissues, which are both, however, relatively uncommon situations.