Homozygous Loss-of-Function Mutations in CCDC134 Are Responsible for a Severe Form of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a primary bone fragility disorder with an estimated prevalence of 1 in 15,000 births. The majority of OI cases are inherited in an autosomal-dominant manner, while 5% to 10% have recessive or X-linked inheritance. Up to now, approximately 5% of OI cases remain without mutation demonstrated, supporting the involvement of other genes in the disease spectrum. By whole-exome sequencing, we identified a homozygous variant (c.2T>C) in CCDC134 gene in three patients from two unrelated families with severe bone fragility that did not respond to bisphosphonate treatment, short stature, and gracile long bones with pseudarthroses but no dentinogenesis imperfecta. CCDC134 encodes a secreted protein widely expressed and implicated in the regulation of some mitogen-activated protein kinases (MAPK) signaling pathway. Western blot and immunofluorescence analyses confirmed the absence of CCDC134 protein in patient cells compared with controls. Furthermore, we demonstrated that CCDC134 mutations are associated with increased Erk1/2 phosphorylation, decreased OPN mRNA and COL1A1 expression and reduced mineralization in patient osteoblasts compared with controls. These data support that CCDC134 is a new gene involved in severe progressive deforming recessive osteogenesis imperfecta (type III). © 2020 American Society for Bone and Mineral Research.

Femoral head vascularisation in Legg-Calvé-Perthes disease: comparison of dynamic gadolinium-enhanced subtraction MRI with bone scintigraphy.

BACKGROUND: It has been reported that MRI using a dynamic gadolinium-enhanced subtraction technique can allow the early identification of ischaemia and the pattern of revascularisation in Legg-Calvé-Perthes (LCP) disease with increased spatial and contrast resolution. Therefore, dynamic gadolinium-enhanced subtraction (DGS) MRI may be a possible non-ionising substitute for bone scintigraphy. OBJECTIVE: The purpose of this prospective study was to compare DGS MRI and bone scintigraphy in the assessment of femoral head perfusion in LCP disease. MATERIALS AND METHODS: Twenty-six DGS MR images and bone scintigraphies of 25 hips in 23 children were obtained at different stages of LCP disease; three stage I, 12 stage II, six stage III and five stage IV (Waldenström classification). The extent of necrosis, epiphyseal revascularisation pathways (lateral pillar, medial pillar, and/or transphyseal perfusion) and metaphyseal changes were analysed. RESULTS: Total agreement between both techniques was noted in the depiction of epiphyseal necrosis (kappa=1), and metaphyseal abnormalities (kappa=0.9). DGS MRI demonstrated better revascularisation in the lateral (kappa=0.62) and medial pillars (kappa=0.52). The presence of basal transphyseal reperfusion was more conspicuous with MRI. CONCLUSIONS: DGS MRI allows early detection of epiphyseal ischaemia and accurate analysis of the different revascularisation patterns. These changes are directly related to the prognosis of LCP disease and can aid therapeutic decision making.

Congenital high scapula.

Congenital high scapula is also known as Sprengel's deformity. The elevation of the scapula is accompanied by its rotation to a varus position. A series of 19 cases is presented, with 4 bilateral cases. A modified Woodward procedure was performed in all the surgical cases using the basic Woodward technique modified by correcting the tilting of the glena. The operative results were judged on cosmetic and functional criteria. The age of the patients and the presence of an omovertebral bone did not influence the results. Associated cervical spine anomalies were of negative prognosis. Results in this series showed only three fair or poor results; the other cases (79%) were all improved cosmetically and functionally with normal shoulder abduction following reorientation of the scapulo-humeral joint.