Osteopoikilosis and multiple exostoses caused by novel mutations in LEMD3 and EXT1 genes respectively - coincidence within one family

<p>Abstract</p> <p>Background</p> <p>Osteopoikilosis is a rare autosomal dominant genetic disorder, characterised by the occurrence of the hyperostotic spots preferentially localized in the epiphyses and metaphyses of the long bones, and in the carpal and tarsal bones <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. Heterozygous <it>LEMD3 </it>gene mutations were shown to be the primary cause of the disease <abbrgrp><abbr bid="B2">2</abbr></abbrgrp>. Association of the primarily asymptomatic osteopokilosis with connective tissue nevi of the skin is categorized as Buschke-Ollendorff syndrome (BOS) <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>. Additionally, osteopoikilosis can coincide with melorheostosis (MRO), a more severe bone disease characterised by the ectopic bone formation on the periosteal and endosteal surface of the long bones <abbrgrp><abbr bid="B4">4</abbr><abbr bid="B5">5</abbr><abbr bid="B6">6</abbr></abbrgrp>. However, not all MRO affected individuals carry germ-line <it>LEMD3 </it>mutations <abbrgrp><abbr bid="B7">7</abbr></abbrgrp>. Thus, the genetic cause of MRO remains unknown. Here we describe a familial case of osteopoikilosis in which a novel heterozygous <it>LEMD3 </it>mutation coincides with a novel mutation in <it>EXT1</it>, a gene involved in aetiology of multiple exostosis syndrome. The patients affected with both <it>LEMD3 </it>and <it>EXT1 </it>gene mutations displayed typical features of the osteopoikilosis. There were no additional skeletal manifestations detected however, various non-skeletal pathologies coincided in this group.</p> <p>Methods</p> <p>We investigated <it>LEMD3 </it>and <it>EXT1 </it>in the three-generation family from Poland, with 5 patients affected with osteopoikilosis and one child affected with multiple exostoses.</p> <p>Results</p> <p>We found a novel c.2203C > T (p.R735X) mutation in exon 9 of <it>LEMD3</it>, resulting in a premature stop codon at amino acid position 735. The mutation co-segregates with the osteopoikilosis phenotype and was not found in 200 ethnically matched controls. Another new substitution G > A was found in <it>EXT1 </it>gene at position 1732 (cDNA) in Exon 9 (p.A578T) in three out of five osteopoikilosis affected family members. Evolutionary conservation of the affected amino acid suggested possible functional relevance, however no additional skeletal manifestations were observed other then those specific for osteopoikilosis. Finally in one member of the family we found a splice site mutation in the <it>EXT1 </it>gene intron 5 (IVS5-2 A > G) resulting in the deletion of 9 bp of cDNA encoding three evolutionarily conserved amino acid residues. This child patient suffered from a severe form of exostoses, thus a causal relationship can be postulated.</p> <p>Conclusions</p> <p>We identified a new mutation in <it>LEMD3 </it>gene, accounting for the familial case of osteopoikilosis. In the same family we identified two novel <it>EXT1 </it>gene mutations. One of them A598T co-incided with the <it>LEMD3 </it>mutation. Co-incidence of <it>LEMD3 </it>and <it>EXT1 </it>gene mutations was not associated with a more severe skeletal phenotype in those patients.</p

Effect of rotation on frontal plane deformity in idiopathic scoliosis

To analyze the effect of rotation on frontal plane deformity in idiopathic scoliosis, 44 patients with idiopathic scoliosis aged 11 to 18 years were examined using standing anteroposterior and true AP radiographs. Axial rotation was measured by computed tomography. Patients were divided into two groups according to Cobb angle: patients with angles comprised group 1 and patients with angles >30 degrees comprised group 2. Cobb angle increased with true-AP projection a mean of 21.2% in group 1 and 16.7% in group 2. Rotation degree was significantly correlated with increasing degree of frontal plane deformity (P.05). These results demonstrate the influence of rotation over frontal plane deformity and is more apparent at curves >30 degrees

A new method to measure vertebral rotation from CT scans

CT measurement methods have good reliability for idiopathic scoliosis transverse plane deformity evaluation. However, because of application difficulties and variations in how these methods are applied, more sensitive methods are needed. This paper presents a new method for measurement of vertebral rotation from tomographic scans. First, the method was subject to clinical, intraobserver and inter-observer analysis. Twenty-three patients with adolescent idiopathic scoliosis were studied to test the clinical reliability of this method. There were no statistical differences between the results of the new method and Ho's method (P = 0.3380) in the clinical study. Intra-observer and inter-observer analysis showed that this method was reliable. An experimental study was then conducted to show the confidence limits of our new method, which were found to be +/- 1.6 degrees, and there was no significant difference between the mean rotation value obtained from CT scans using our new method and that obtained using the mechanical method. These results suggest that our new method is a simple, practical and reliable method for measurement of vertebral rotation from CT scans

Forty-two year survival with bilateral Judet hip prostheses

In this case report, a 70-year-old man is presented who had begun to suffer from ankylosing spondylitis when he was 12 years old and had been operated on be cause of bilateral hip ankylosis at the age of 21 years. The interesting aspect of this case is that both hips were replaced with Judet type prostheses, which survived for 42 years

Modeling and stress analyses of a normal foot-ankle and a prosthetic foot-ankle complex

Total ankle replacement (TAR) is a relatively new concept and is becoming more popular for treatment of ankle arthritis and fractures. Because of the high costs and difficulties of experimental studies, the developments of TAR prostheses are progressing very slowly. For this reason, the medical imaging techniques such as CT, and MR have become more and more useful. The finite element method (FEM) is a widely used technique to estimate the mechanical behaviors of materials and structures in engineering applications. FEM has also been increasingly applied to biomechanical analyses of human bones, tissues and organs, thanks to the development of both the computing capabilities and the medical imaging techniques. 3-D finite element models of the human foot and ankle from reconstruction of MR and CT images have been investigated by some authors. In this study, data of geometries (used in modeling) of a normal and a prosthetic foot and ankle were obtained from a 3D reconstruction of CT images. The segmentation software, MIMICS was used to generate the 3D images of the bony structures, soft tissues and components of prosthesis of normal and prosthetic ankle-foot complex. Except the spaces between the adjacent surface of the phalanges fused, metatarsals, cuneiforms, cuboid, navicular, talus and calcaneus bones, soft tissues and components of prosthesis were independently developed to form foot and ankle complex. SOLIDWORKS program was used to form the boundary surfaces of all model components and then the solid models were obtained from these boundary surfaces. Finite element analyses software, ABAQUS was used to perform the numerical stress analyses of these models for balanced standing position. Plantar pressure and von Mises stress distributions of the normal and prosthetic ankles were compared with each other. There was a peak pressure increase at the 4th metatarsal, first metatarsal and talus bones and a decrease at the intermediate cuneiform and calcaneus bones, in prosthetic ankle-foot complex compared to normal one. The predicted plantar pressures and von Misses stress distributions for a normal foot were consistent with other FE models given in the literature. The present study is aimed to open new approaches for the development of ankle prosthesis

Bilateral congenital subluxation of the proximal tibiofibular joint with magnetic resonance imaging findings: a case report

There appear to be no criteria in the differential diagnosis of traumatic and congenital subluxation of the proximal tibiofibular joint in the literature. We report a case with bilateral congenital subluxation of the proximal tibiofibular joint and describe the magnetic resonance imaging features for the differential diagnosis

Ipsilateral hip pain and femoral shaft fractures: is there any relationship?

BACKGROUND: High-energy traumas are common occurrences worldwide. The rate of overlooked neck fractures in polytrauma cases is also high. Previous studies have shown that articular hip pathologies, particularly neck fractures, are associated with fractures of the femoral shaft. This study sets out to describe cases of intra-articular hip pathology following traumatic femoral shaft fracture. Thus, the present study aims to investigate the relationship between ipsilateral hip pain and femoral shaft fractures

Extraarticular pigmented villonodular synovitis of the hip

Pigmented villonodular synovitis of any joint in the extraarticular region is very rare. Its clinical and radiological differential diagnosis is difficult due to exhibiting findings of any soft tissue tumor. Here we report an extrarticular pigmented villonodular synovitis case of the hip of a five-year-old boy, with its radiological and histopathological aspects. The mass was completely extraarticular and was identified histologically and radiologically as pigmented villonodular synovitis. Six months after marginal excision, the lesion recurred. The physicians can face such cases of pigmented villonodular synovitis presenting with unusual extraarticular location, and the preferred excision should be wide to avoid possible recurrences

The evaluation of the proximal tibiofibular joint for patients with lateral knee pain

In contrast to important functions of the proximal tibiofibular joint (PTFJ), there appear a few clinical and radiological studies concerning the PTFJ pathologies. Although almost all of the joints have been investigated in detail by MRI, review of the literature reveals none on the pathologies of PTFJ. Thirty-eight knees of 32 patients with lateral knee pain were evaluated clinically and radiologically. All had tenderness over the PTFJ and lateral hamstring tightness. MRI examination revealed effusion of the PTFJ in 22 knees and partial ruptures of anterior or posterior tibiofibular ligament, lateral collateral ligament or biceps femoris tendon in 25 knees. All patients were treated by manipulative physiotherapy of the PTFJ and strengthening and stretching exercises of the surrounding structures. All patients were followed-up 12-36 months (mean 28 months) after the treatment protocol, and complete relief of the symptoms was recorded in 28 of the 38 knees. Although spontaneous pain was not present in five patients, there was tenderness over the PTFJ by palpation. No change in the symptoms was recorded in five patients. These results suggest that PTFJ pathologies should be kept in mind in the evaluation of lateral knee pain and MRI examination provides useful information. (C) 2003 Elsevier B.V. All rights reserved