Genomic deletion of a long-range bone enhancer misregulatessclerostin in Van Buchem disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loots, Gabriela G.; Kneissel, Michaela; Keller, Hansjoerg

2005-04-15

Mutations in distant regulatory elements can negatively impact human development and health, yet due to the difficulty of detecting these critical sequences we predominantly focus on coding sequences for diagnostic purposes. We have undertaken a comparative sequence-based approach to characterize a large noncoding region deleted in patients affected by Van Buchem disease (VB), a severe sclerosing bone dysplasia. Using BAC recombination and transgenesis we characterized the expression of human sclerostin (sost) from normal (hSOSTwt) or Van Buchem(hSOSTvb D) alleles. Only the hSOSTwt allele faithfully expressed high levels of human sost in the adult bone and impacted bone metabolism, consistent withmore » the model that the VB noncoding deletion removes a sost specific regulatory element. By exploiting cross-species sequence comparisons with in vitro and in vivo enhancer assays we were able to identify a candidate enhancer element that drives human sost expression in osteoblast-like cell lines in vitro and in the skeletal anlage of the E14.5 mouse embryo, and discovered a novel function for sclerostin during limb development. Our approach represents a framework for characterizing distant regulatory elements associated with abnormal human phenotypes.« less

Cemento-osseous dysplasia of the jaw bones: key radiographic features

PubMed Central

Alsufyani, NA; Lam, EWN

2011-01-01

Objective The purpose of this study is to assess possible diagnostic differences between general dentists (GPs) and oral and maxillofacial radiologists (RGs) in the identification of pathognomonic radiographic features of cemento-osseous dysplasia (COD) and its interpretation. Methods Using a systematic objective survey instrument, 3 RGs and 3 GPs reviewed 50 image sets of COD and similarly appearing entities (dense bone island, cementoblastoma, cemento-ossifying fibroma, fibrous dysplasia, complex odontoma and sclerosing osteitis). Participants were asked to identify the presence or absence of radiographic features and then to make an interpretation of the images. Results RGs identified a well-defined border (odds ratio (OR) 6.67, P < 0.05); radiolucent periphery (OR 8.28, P < 0.005); bilateral occurrence (OR 10.23, P < 0.01); mixed radiolucent/radiopaque internal structure (OR 10.53, P < 0.01); the absence of non-concentric bony expansion (OR 7.63, P < 0.05); and the association with anterior and posterior teeth (OR 4.43, P < 0.05) as key features of COD. Consequently, RGs were able to correctly interpret 79.3% of COD cases. In contrast, GPs identified the absence of root resorption (OR 4.52, P < 0.05) and the association with anterior and posterior teeth (OR 3.22, P = 0.005) as the only key features of COD and were able to correctly interpret 38.7% of COD cases. Conclusions There are statistically significant differences between RGs and GPs in the identification and interpretation of the radiographic features associated with COD (P < 0.001). We conclude that COD is radiographically discernable from other similarly appearing entities only if the characteristic radiographic features are correctly identified and then correctly interpreted. PMID:21346079

Cemento-osseous dysplasia of the jaw bones: key radiographic features.

PubMed

Alsufyani, N A; Lam, E W N

2011-03-01

The purpose of this study is to assess possible diagnostic differences between general dentists (GPs) and oral and maxillofacial radiologists (RGs) in the identification of pathognomonic radiographic features of cemento-osseous dysplasia (COD) and its interpretation. Using a systematic objective survey instrument, 3 RGs and 3 GPs reviewed 50 image sets of COD and similarly appearing entities (dense bone island, cementoblastoma, cemento-ossifying fibroma, fibrous dysplasia, complex odontoma and sclerosing osteitis). Participants were asked to identify the presence or absence of radiographic features and then to make an interpretation of the images. RGs identified a well-defined border (odds ratio (OR) 6.67, P < 0.05); radiolucent periphery (OR 8.28, P < 0.005); bilateral occurrence (OR 10.23, P < 0.01); mixed radiolucent/radiopaque internal structure (OR 10.53, P < 0.01); the absence of non-concentric bony expansion (OR 7.63, P < 0.05); and the association with anterior and posterior teeth (OR 4.43, P < 0.05) as key features of COD. Consequently, RGs were able to correctly interpret 79.3% of COD cases. In contrast, GPs identified the absence of root resorption (OR 4.52, P < 0.05) and the association with anterior and posterior teeth (OR 3.22, P = 0.005) as the only key features of COD and were able to correctly interpret 38.7% of COD cases. There are statistically significant differences between RGs and GPs in the identification and interpretation of the radiographic features associated with COD (P < 0.001). We conclude that COD is radiographically discernable from other similarly appearing entities only if the characteristic radiographic features are correctly identified and then correctly interpreted.

Case report 834: Chronic sclerosing osteomyelitis of the mandible with long bone periostitis.

PubMed

Stewart, A; Carneiro, R; Pollock, L; Shaw, D

1994-04-01

We present the case of a patient with primary chronic osteomyelitis of the mandible, the radiological appearance of which is compatible with a diagnosis of chronic sclerosing osteomyelitis. The accompanying femoral and tibial periosteal reactive new bone formation and the benign clinical course suggest that this presentation may represent a form of chronic multifocal osteomyelitis.

Glenoid labrum ossification and mechanical restriction of joint motion: extraosseous manifestations of melorheostosis.

PubMed

Subhas, N; Sundaram, M; Bauer, T W; Seitz, W H; Recht, M P

2008-02-01

We report a case of a 47-year-old man who presented with progressive loss of motion and pain in the right shoulder. Radiographs of the shoulder demonstrated dense ossification in the glenoid and humeral head with extension into the periarticular soft tissues. CT and MRI scans confirmed the radiographic findings and also revealed ossification of the glenoid labrum. A radiographic diagnosis of melorheostosis, an uncommon benign sclerosing bone dysplasia, was made. Because of the patient's severe symptomatology, he underwent total shoulder arthroplasty. Histological analysis of the resected masses was consistent with melorheostosis with a few areas covered by a cartilage cap. This case illustrates several uncommon but important features of melorheostosis, including mechanical obstruction of joint motion requiring joint replacement, ossification of the glenoid labrum, and cartilage-covering portions of the intra-articular masses, not to be confused with cartilage-producing tumors.

Bone scintigraphy elucidates different metabolic stages of melorheostosis.

PubMed

Izadyar, Sina; Gholamrezanezhad, Ali

2012-01-01

Melorheostosis is a rare benign non-hereditary sclerosing dysplasia involving the bone, often in a sclerotomal distribution. we report the case of a 27 years old lady with painful swelling of the left hand and forearm lasting for almost 15 years. The patient experienced aggravation of symptoms and limitation of motion during the past two months. Radiographic assessment revealed hyperostosis involving the left 3(rd) and 4(th) metacarpal bones and corresponding digits as well as the left ulna and distal humerus, with no soft tissue ossification. Angiographic and blood pool images of bone scintigraphy showed increased activity of mid-metacarpal region, corresponding to the sclerotom C-8. Delayed static views showed increased radiotracer uptake of the left 4(th) metacarpal bone and the corresponding digit as well as the left ulna and humerus, but no abnormal osteoblastic activity of the 3(rd) left metacarpal and digit. Histopathologic assessment confirmed the diagnosis of Melorheostosis. The case confirms that even in the same sclerotomal distribution, the multiple foci of involvement can present in different metabolic stages. In fact, the disease does not progress uniformly and different lesions can be seen in dissimilar stages of activity. Hence, metabolic imaging can be important to unmask which of the radiographically detected bony lesions are metabolically active and have the potential to be the source of current patient's symptoms and which of them are old, metabolically inactive and silent lesions, which are not clinically relevant to the patient's complaints.

Bone scintigraphy elucidates different metabolic stages of melorheostosis

PubMed Central

Izadyar, Sina; Gholamrezanezhad, Ali

2012-01-01

Melorheostosis is a rare benign non-hereditary sclerosing dysplasia involving the bone, often in a sclerotomal distribution. we report the case of a 27 years old lady with painful swelling of the left hand and forearm lasting for almost 15 years. The patient experienced aggravation of symptoms and limitation of motion during the past two months. Radiographic assessment revealed hyperostosis involving the left 3rd and 4th metacarpal bones and corresponding digits as well as the left ulna and distal humerus, with no soft tissue ossification. Angiographic and blood pool images of bone scintigraphy showed increased activity of mid-metacarpal region, corresponding to the sclerotom C-8. Delayed static views showed increased radiotracer uptake of the left 4th metacarpal bone and the corresponding digit as well as the left ulna and humerus, but no abnormal osteoblastic activity of the 3rd left metacarpal and digit. Histopathologic assessment confirmed the diagnosis of Melorheostosis. The case confirms that even in the same sclerotomal distribution, the multiple foci of involvement can present in different metabolic stages. In fact, the disease does not progress uniformly and different lesions can be seen in dissimilar stages of activity. Hence, metabolic imaging can be important to unmask which of the radiographically detected bony lesions are metabolically active and have the potential to be the source of current patient's symptoms and which of them are old, metabolically inactive and silent lesions, which are not clinically relevant to the patient's complaints. PMID:22514755

Cystic fibrous dysplasia in the long bone.

PubMed

Bahk, Won-Jong; Kang, Yong-Koo; Rhee, Seung-Koo; Chung, Yang-Guk; Lee, An-Hee; Bahk, Yong-Whee

2007-10-01

Prominent osteolysis associated with "ground glass" density of fibrous dysplasia may indicate cystic change or sarcomatous transformation. This complication has been reported only sporadically in the long bones. This article presents clinical, radiographic, and pathologic findings, and outcome of simple curettage and bone graft observed in a series of 8 patients with prominent cystic fibrous dysplasia of the long bone. Magnetic resonance imaging features provide a basis for separation of benign cystic change from malignant transformation. However, biopsy is necessary to distinguish nonspecific cystic degeneration from secondary aneurysmal bone cyst. Simple curettage with allo-chip-bone graft is an effective treatment for cystic fibrous dysplasia.

'Laminopathies': A wide spectrum of human diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Worman, Howard J.; Bonne, Gisele; Universite Pierre et Marie Curie-Paris 6, Faculte de medecine, Paris F-75013

2007-06-10

Mutations in genes encoding the intermediate filament nuclear lamins and associated proteins cause a wide spectrum of diseases sometimes called 'laminopathies.' Diseases caused by mutations in LMNA encoding A-type lamins include autosomal dominant Emery-Dreifuss muscular dystrophy and related myopathies, Dunnigan-type familial partial lipodystrophy, Charcot-Marie-Tooth disease type 2B1 and developmental and accelerated aging disorders. Duplication in LMNB1 encoding lamin B1 causes autosomal dominant leukodystrophy and mutations in LMNB2 encoding lamin B2 are associated with acquired partial lipodystrophy. Disorders caused by mutations in genes encoding lamin-associated integral inner nuclear membrane proteins include X-linked Emery-Dreifuss muscular dystrophy, sclerosing bone dysplasias, HEM/Greenberg skeletal dysplasiamore » and Pelger-Huet anomaly. While mutations and clinical phenotypes of 'laminopathies' have been carefully described, data explaining pathogenic mechanisms are only emerging. Future investigations will likely identify new 'laminopathies' and a combination of basic and clinical research will lead to a better understanding of pathophysiology and the development of therapies.« less

Co-occurence of florid cemento-osseous dysplasia and simple bone cyst: a case report.

PubMed

Rao, Kumuda Arvind; Shetty, Shishir Ram; Babu, Subhas G; Castelino, Renita Lorina

2011-01-01

The purpose of this report is to present a rare case of co-occurrence of florid cemento-osseous dysplasia with simple bone cyst in a middle aged Asian woman. Most of the reported cases are isolated cases of simple bone cyst or florid cemento-osseous dysplasia, but co-occurrence of these two entities is extremely rare. The authors report a 41 year old female patient with co-occurrence of mandibular florid cemento-osseous dysplasia with simple bone cyst. A thorough clinical and radiological examination was carried out. It was diagnosed mandibular cyst with possible co-occurrence of florid cemento-osseous dysplasia. Surgical exploration of the multilocular lesion was applied. Since, the patient was symptomatic at the time of presentation utmost caution was taken during the surgical procedure as florid cemento-osseous dysplasia is associated with hypo-vascularity of the affected bone. Based on histopathological, as well as supporting clinico-radiological findings a confirmative diagnosis of florid cemento-osseous dysplasia co-occurring with simple bone cyst was made. Patient was followed-up for a period of six months and was reported to be asymptomatic. Timely diagnosis and well planned treatment is important to obtain a good prognosis when a rare co-occurrence of two or more bone lesions affects the jaws.

Detecting dysplasia using white light endoscopy or chromoendoscopy in ulcerative colitis patients without primary sclerosing cholangitis: A systematic review and meta-analysis.

PubMed

Azizi, Saeed; Al-Rubaye, Hussein; Turki, Mohammed Adil A; Siddiqui, Muhammad R Sameem; Shanmuganandan, Arun P; Ehsanullah, Bushra; Brar, Ranjeet; Abulafi, Al-Mutaz

2018-04-01

Endoscopic examinations are a vital diagnostic tool for dysplasia. Establishing the precision of different modes of examination is essential due to the disparate pick-up rates of dysplasia. The aim of this article was to establish the pick-up rates of dysplastic or cancerous lesions using white light endoscopy (WLE) and random/targeted biopsies, or chromoendoscopy (CE), in patients with ulcerative colitis (UC) without primary sclerosing (PSC) or Crohn's disease (CD). A systematic review to identify all studies up to November 2017, without language restriction, was conducted from PubMed, the Cochrane Controlled Trials Register (1960-2017), MEDLINE, CINAHL and EMBASE (1981-2017). MeSH and text word terms used included "ulcerative colitis", "dysplasia", "random biopsy", "targeted biopsy", "colonoscopy", "white light", and "chromoendoscopy". Further searches were performed using the bibliographies of these articles. All studies reporting on colonoscopy detection rates of dysplasia and cancers in UC without involvement of PSC or CD were included. There was no age restriction to include patients. Outcome data were extracted by 2 authors independently using outcome measures defined a priori. Quality assessment was performed using the Newcastle-Ottawa scales. Data were extracted and analysed according to meta-analytical techniques using comprehensive meta-analysis. The pooled overall pick-up rate of dysplastic/cancerous lesions on WLE random biopsies was 5.6% [Event rate 0.06 (0.01, 0.23), df = 4, I2 = 94%]. Using a combined random and targeted approach with WLE the incidence was 5.1% [Event rate 0.05 (0.03, 0.09), df = 4, I2 = 96%]. One study reported on CE and found a 7% pick-up rate for dysplastic lesions. Endoscopic examination of UC patients without PSC identifies dysplastic or cancerous lesions in 5-7% of cases. WLE and random biopsies may pick-up a similar number of lesions to targeted biopsies, however the number of biopsies may need to be greater to achieve this equivalence. CE has a slightly higher pick-up rate. Further comparative studies are required to strengthen the body of evidence. Copyright © 2018. Published by Elsevier Ltd.

Prenatal diagnosis of boomerang dysplasia.

PubMed

Wessels, Marja W; Den Hollander, Nicolette S; De Krijger, Ronald R; Bonifé, Luisa; Superti-Furga, Andrea; Nikkels, Peter G; Willems, Patrick J

2003-10-01

Boomerang dysplasia, atelosteogenesis type 1 and Piepkorn dysplasia are bone dysplasias with an overlapping clinical spectrum characterized by deficient formation and ossification of specific elements of the skeleton. Typical symptoms include micromelia with diminished ossification, and a characteristic bowed and boomerang-like aspect of the long tubular bones. We report here a new case of boomerang dysplasia, which was detected prenatally in the 16th week of gestation by ultrasound. Copyright 2003 Wiley-Liss, Inc.

Clinical features and management of primary sclerosing cholangitis

PubMed Central

Silveira, Marina G; Lindor, Keith D

2008-01-01

Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in cirrhosis and need for liver transplantation and reduced life expectancy. The majority of cases occur in young and middle-aged men, often in association with inflammatory bowel disease. The etiology of primary sclerosing cholangitis includes immune-mediated components and elements of undefined nature. No effective medical therapy has been identified. The multiple complications of primary sclerosing cholangitis include metabolic bone disease, dominant strictures, bacterial cholangitis, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of primary sclerosing cholangitis. Liver transplantation is currently the only life-extending therapeutic alternative for patients with end-stage disease, although recurrence in the allografted liver has been described. A PSC-like variant attracting attention is cholangitis marked by raised levels of the immunoglobulin G4 subclass, prominence of plasma cells within the lesions, and steroid responsiveness. PMID:18528931

[Advances in bone dysplasias].

PubMed

Borrego, E; Farrington, D M; Downey, F J

2014-01-01

The prevalence of bone dysplasias is estimated to be one case per 1,000 inhabitants, which suggests that, at some point in the career of an orthopaedic surgeon, he will face with one of these patients. The aim of this paper is to review the general aspects of bone dysplasias and focus on those, which due to their frequency and importance, we consider most relevant (achondroplasia, multiple epiphyseal dysplasia, spondyloepiphyseal dysplasia, osteogenesis imperfecta), reviewing their fundamental features and the latest therapeutic advances. There is no cure for these diseases, so early diagnosis and appropriate therapeutic management, becomes the key to improving quality of life of these patients. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

Ulcerative colitis-associated colorectal cancer

PubMed Central

Yashiro, Masakazu

2014-01-01

The association between ulcerative colitis (UC) and colorectal cancer (CRC) has been acknowledged. One of the most serious and life threatening consequences of UC is the development of CRC (UC-CRC). UC-CRC patients are younger, more frequently have multiple cancerous lesions, and histologically show mucinous or signet ring cell carcinomas. The risk of CRC begins to increase 8 or 10 years after the diagnosis of UC. Risk factors for CRC with UC patients include young age at diagnosis, longer duration, greater anatomical extent of colonic involvement, the degree of inflammation, family history of CRC, and presence of primary sclerosing cholangitis. CRC on the ground of UC develop from non-dysplastic mucosa to indefinite dysplasia, low-grade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma. Colonoscopy surveillance programs are recommended to reduce the risk of CRC and mortality in UC. Genetic alterations might play a role in the development of UC-CRC. 5-aminosalicylates might represent a favorable therapeutic option for chemoprevention of CRC. PMID:25469007

High-Dose Ursodeoxycholic Acid Is Associated With the Development of Colorectal Neoplasia in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

PubMed Central

Eaton, John E.; Silveira, Marina G.; Pardi, Darrell S.; Sinakos, Emmanouil; Kowdley, Kris V.; Luketic, Velimir A.C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Lindor, Keith D.

2011-01-01

OBJECTIVES Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28–30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30–20.10, P=0.02). CONCLUSIONS Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC. PMID:21556038

Effect of acetabular reinforcement ring with hook for acetabular dysplasia clarified by three-dimensional finite element analysis.

PubMed

Zhao, Xin; Chosa, Etsuo; Yamako, Go; Watanabe, Shinji; Deng, Gang; Totoribe, Koji

2013-12-01

The objective of this study was to biomechanically determine the effect of the severity of acetabular dysplasia, number and positions of screws and type of bone graft material used on the initial fixation strength of the acetabular reinforcement ring with hook (Ganz ring) using the finite element method. Relative micromotion increased as the severity of acetabular dysplasia increased and tended to decrease as the number of screws increased, but varied according to screw placement position. Increased strength of the bone graft material led to decreased relative micromotion. Biomechanically, the Ganz ring can be placed securely using 3 screws in patients with Crowe 1 dysplasia. However, in patients with Crowe 2 or higher dysplasia, it is necessary to spread at least 4 screws across an area of good host bone. © 2013.

Neuroimaging findings of extensive sphenoethmoidal dysplasia in NF1.

PubMed

Tam, Allison; Sliepka, Joseph M; Bellur, Sunil; Bray, Collin Douglas; Lincoln, Christie M; Nagamani, Sandesh C S

2018-05-16

Whereas isolated sphenoid wing dysplasia (SWD) is a well-known clinical feature in neurofibromatosis 1 (NF1), extensive cranial defects involving multiple bones have been rarely reported in this disorder. In this report, we describe the clinical course of a 20-year-old male with NF1 and an extensive cranial bone dysplasia. The large sphenoethmoidal defect was associated with transethmoidal and orbital cephalocele as well as inferolateral herniation of the frontal lobe. In spite of the large defect, the individual did not have any symptoms or complications resulting from the osteopathy. We review the current knowledge of the pathogenesis and management of cranial bone dysplasia in NF1. Copyright © 2018 Elsevier Inc. All rights reserved.

Grebe dysplasia - prenatal diagnosis based on rendered 3-D ultrasound images of fetal limbs.

PubMed

Goncalves, Luis F; Berger, Julie A; Macknis, Jacqueline K; Bauer, Samuel T; Bloom, David A

2017-01-01

Grebe dysplasia is a rare skeletal dysplasia characterized by severe acromesomelic shortening of the long bones in a proximal to distal gradient of severity, with bones of the hands and feet more severely affected than those of the forearms and legs, which in turn are more severely affected than the humeri and femora. In addition, the bones of the lower extremities tend to be more severely affected than the bones of the upper extremities. Despite the severe skeletal deformities, the condition is not lethal and surviving individuals can have normal intelligence. Herein we report a case of Grebe dysplasia diagnosed at 20 weeks of gestation. Rendered 3-D ultrasound images of the fetal limbs, particularly of the characteristic tiny and globular-looking fingers and toes, were instrumental in accurately characterizing the phenotype prenatally.

Sclerosteosis involving the temporal bone: histopathologic aspects.

PubMed

Nager, G T; Hamersma, H

1986-01-01

Sclerosteosis is a rare, potentially lethal, autosomal recessive, progressive craniotubular sclerosing bone dysplasia with characteristic facial and skeletal features. The temporal bone changes include a marked increase in overall size, extensive sclerosis, narrowing of the external auditory canal, and severe constriction of the internal auditory meatus, fallopian canal, eustachian tube, and middle ear cleft. Attenuation of the bony canals of the 9th, 10th, and 11th cranial nerves, reduction in size of the internal carotid artery, and severe obliteration of the sigmoid sinus and jugular bulb also occur. Loss of hearing, generally bilateral, is a frequent symptom. It often manifests in early childhood and initially is expressed as sound conduction impairment. Later, a sensorineural hearing loss and loss of vestibular nerve function often develop. Impairment of facial nerve function is another feature occasionally present at birth. In the beginning, a unilateral intermittent facial weakness may occur which eventually progresses to a bilateral permanent facial paresis. The histologic examination of the temporal bones from a patient with sclerosteosis explains the mechanisms involved in the progressive impairment of sound conduction and loss of cochlear, vestibular, and facial nerve function. There is a decrease of the arterial blood supply to the brain and an obstruction of the venous drainage from it. The histopathology reveals the obstacles to decompression of the middle ear cleft, ossicular chain, internal auditory and facial canals, and the risks, and in many instances the contraindications, to such procedures. On the other hand, decompression of the sigmoid sinus and jugular bulb should be considered as an additional life-saving procedure in conjunction with the prophylactic craniotomy recommended in all adult patients.

Assessment of bone dysplasia by micro-CT and glycosaminoglycan levels in mouse models for mucopolysaccharidosis type I, IIIA, IVA, and VII

PubMed Central

Rowan, Daniel J.; Tomatsu, Shunji; Grubb, Jeffrey H.; Montaño, Adriana M.; Sly, William S.

2012-01-01

Summary Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases caused by mutations in lysosomal enzymes involved in degradation of glycosaminoglycans (GAGs). Patients with MPS grow poorly and become physically disabled due to systemic bone disease. While many of the major skeletal effects in mouse models for MPS have been described, no detailed analysis that compares GAGs levels and characteristics of bone by micro-CT has been done. The aims of this study were to assess severity of bone dysplasia among four MPS mouse models (MPS I, IIIA, IVA and VII), to determine the relationship between severity of bone dysplasia and serum keratan sulfate (KS) and heparan sulfate (HS) levels in those models, and to explore the mechanism of KS elevation in MPS I, IIIA, and VII mouse models. Clinically, MPS VII mice had the most severe bone pathology; however, MPS I and IVA mice also showed skeletal pathology. MPS I and VII mice showed severe bone dysplasia, higher bone mineral density, narrowed spinal canal, and shorter sclerotic bones by micro-CT and radiographs. Serum KS and HS levels were elevated in MPS I, IIIA, and VII mice. Severity of skeletal disease displayed by micro-CT, radiographs and histopathology correlated with the level of KS elevation. We showed that elevated HS levels in MPS mouse models could inhibit N-acetylgalactosamine-6-sulfate sulfatase enzyme. These studies suggest that KS could be released from chondrocytes affected by accumulation of other GAGs and that KS could be useful as a biomarker for severity of bone dysplasia in MPS disorders. PMID:22971960

Two familial cases with a lethal gracile bone dysplasia and intrauterine growth retardation.

PubMed

Korniszewski, Lech; Arbuckle, Susan; Kozlowski, Kazimierz

2003-05-01

A number of more or less distinct entities with low birth weight and abnormal radiographic appearances have been identified. We studied two sisters who were unusual because of severe intrauterine growth restriction, absence of growth after birth, decrease of pre- and postnatal spontaneous mobility, and early fatal outcome. The chondro-osseous morphology documented a distinctive osteochondrodysplasia. The radiographic examination was superficially similar to gracile bone dysplasias but was inconsistent with any known types of this group. These two patients appear to have a unique gracile bone dysplasia. Copyright 2003 Wiley-Liss, Inc.

Headache Attributed to Fibrous Dysplasia of the Ethmoid Bone Mimicking Menstrual Migraine Without Aura.

PubMed

Kim, Kyung Soo

2016-06-01

The authors experienced a patient of fibrous dysplasia originating from the ethmoid bone which presented with severe headache with some features suggestive of menstrual migraine without aura. Fibrous dysplasia originating from the ethmoid bone is a rare disease entity, but may cause severe headache that can be misdiagnosed as "menstrual migraine" because of similar symptoms in female patients. Because the primary objective of surgery is symptomatic relief, conservative transnasal endoscopic approach may be considered an alternative to more invasive external surgical techniques in carefully selected patients, especially originating from the nasal cavity and paranasal sinuses.

WHO is in and WHO is out of the mouth, salivary glands, and jaws sections of the 4th edition of the WHO classification of head and neck tumours.

PubMed

Kennedy, R A

2018-02-01

This review of changes to the 4th edition of the WHO classification of head and neck tumours focuses on their impact on the surgical care of diseases that affect the salivary glands, jaws, and oral cavity. Updates to the chapter on the salivary glands include the addition of secretory carcinoma and sclerosing polycystic adenosis. The odontogenic cysts are back, and the odontogenic keratocyst is listed among them, as it has now lost its brief and confusing designation as a neoplasm. The newly-defined sclerosing odontogenic carcinoma and primordial odontogenic tumour have been added. Oropharyngeal tumours have been separated from those of the oral cavity, which reflects the importance of HPV in carcinoma of the tonsils. The problems of grading oral epithelial dysplasia persist. Copyright © 2017 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Cleidocranial dysplasia

PubMed Central

Dixit, Ramakant; Dixit, Kalpana; Paramez, A. R.

2010-01-01

Cleidocranial dysplasia is a rare autosomal dominant condition with generalized dysplasia of bone, characterized by delayed closer of cranial sutures, hypoplastic or aplastic clavicles, short stature, dental abnormalities and a variety of other skeletal abnormalities. We present a seven-year-old female child presenting with classical features of cleidocranial dysplasia. PMID:20931042

Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population.

PubMed

Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

2015-01-01

Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias.

Comparative X-ray morphometry of prenatal osteogenesis imperfecta type 2 and thanatophoric dysplasia: a contribution to prenatal differential diagnosis.

PubMed

Bondioni, Maria Pia; Pazzaglia, Ugo Ernesto; Izzi, Claudia; Di Gaetano, Giuseppe; Laffranchi, Francesco; Baldi, Maurizia; Prefumo, Federico

2017-11-01

The purpose of the paper was to assess the morphometric parameters to improve the specificity of the ultrasound (US) signs for the early differential diagnosis between two lethal dysplasias, as thanatophoric dysplasia (TD) and osteogenesis imperfecta type 2 (OI-2). The diaphyseal length and the bowed shape of long bones associated with vertebral body dimension assessment were investigated in a group of 14 pregnancy terminations carried out in the time period 2007-2013. The definitive diagnosis was established after pregnancy termination by means of skeletal standardized X-rays, histopathology and gene analysis. TD and OI-2 long bones were significantly shorter than controls. No significant differences were observed between the two dysplasias. The bowing angle was higher in OI-2; a true angulation or eventually axial displacement was present only in the latter. Furthermore, they did not show any evidence of vertebral collapse. The thanatophoric dysplasia presented less bowed long bones, and never true angulation. The spine was steadily characterized by flattened anterior vertebral bodies. Long bone shortening is not a sufficient and accurate sign for early sonographic differential diagnosis between TD and OI-2. Angled diaphysis, axial diaphyseal displacement and a conserved vertebral body height in the prenatal period support the diagnosis of osteogenesis imperfecta type 2, while moderately regular bowed diaphysis associated with platyspondyly that of thanatophoric dysplasia.

Locally Aggressive Fibrous Dysplasia Mimicking Malign Calvarial Lesion.

PubMed

Ogul, Hayri; Keskin, Emine

2018-05-01

Fibrous dysplasia is an unusual benign bone tumor. It is divided into 3 groups as monostotic, polyostotic, and craniofacial form. The authors reported an unusual patient with fibrous dysplasia with an aggressive radiologic appearance.

Case report: Emergency department diagnosis of melorheostosis in the upper extremity: a rare disease with an unusual presentation.

PubMed

Murano, Tiffany; Egarian, Michele

2012-10-01

Melorheostosis is a rare disease that affects fewer than 1:1,000,000 persons worldwide and most typically affects the lower extremities. It is a non-hereditary disease that may be debilitating due to chronic pain, contractures of the soft tissue, and even shortening of the affected limbs. Although it most commonly occurs in the lower extremities, melorheostosis has been reported in various locations throughout the body. This case report describes a patient who presented to the Emergency Department (ED) with this rare disease in an uncommonly affected bone. The patient was a 21-year-old man who presented to the ED with pain in his left upper extremity that he attributed to playing sports 3 days before presentation. Plain films revealed periosteal hyperostosis typical of melorheostosis in several of his carpals, metacarpals, and phalanges, as well as the humerus and ulna. The patient was discharged with orthopedic follow-up and pain medication. Melorheostosis is a rare disease that has characteristic radiographic findings likened to the appearance of melting wax flowing down the side of a candle. In certain cases, the disease can be debilitating and may require chronic pain management and even operative intervention. If this diagnosis is made in the ED, the emergency physician should provide adequate pain management and refer the patient to an orthopedic specialist for a work-up to rule out other sclerosing bone dysplasias. Copyright © 2012 Elsevier Inc. All rights reserved.

The surgical management of fibrous dysplasia of bone.

PubMed

Stanton, Robert P; Ippolito, Ernesto; Springfield, Dempsey; Lindaman, Lynn; Wientroub, Shlomo; Leet, Arabella

2012-05-24

The surgical management of Polyostotic Fibrous Dysplasia (FD) of bone is technically demanding. The most effective methods to manage the associated bone deformity remain unclear. The marked variation in the degree and pattern of bone involvement has made it difficult to acquire data to guide the surgeon's approach to these patients. In light of the paucity of data, but need for guidance, recognized experts in the management of these patients came together at the National Institutes of Health in Bethesda, Maryland as part of an International meeting to address issues related to fibrous dysplasia of bone to discuss and refine their recommendations regarding the surgical indications and preferred methods for the management of these challenging patients. The specific challenges, recommended approaches, and "lessons learned" are presented in hopes that surgeons faced with typical deformities can be guided in the surgical reconstruction of both children and adults with FD.

Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population

PubMed Central

Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

2015-01-01

Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias. PMID:26488291

Spindle Cell Rhabdomyosarcoma of Bone with FUS-TFCP2 Fusion: Confirmation of a Very Recently Described Rhabdomyosarcoma Subtype.

PubMed

Dashti, Nooshin K; Wehrs, Rebecca N; Thomas, Brittany C; Nair, Asha; Davila, Jaime; Buckner, Jan C; Martinez, Anthony P; Sukov, William R; Halling, Kevin C; Howe, Benjamin M; Folpe, Andrew L

2018-05-14

Rhabdomyosarcomas of bone are extremely rare, with fewer than 10 reported cases. A very rare subtype of spindle cell/sclerosing rhabdomyosarcoma harboring a FUS-TFCP2 fusion and involving both soft tissue and bone locations has very recently been reported. We report only the fourth case of this unusual, clinically aggressive rhabdomyosarcoma. A previously-well 72-year old male presented with a destructive lesion of the mandible. Morphological and immunohistochemical study of a needle biopsy and the subsequent resection showed a spindle cell rhabdomyosarcoma. RNA-seq, RT-PCR and FISH confirmed the presence of the FUS-TFCP2 fusion. Spindle cell rhabdomyosarcomas carrying the FUS-TFCP2 fusion are very rare rhabdomyosarcoma variants with osseous predilection. The classification and differential diagnosis of this unusual molecular variant of spindle cell/ sclerosing rhabdomyosarcoma are discussed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Successful treatment of pain in melorheostosis with zoledronate, with improvement on bone scintigraphy.

PubMed

Slimani, Samy; Nezzar, Adlen; Makhloufi, Hachemi

2013-06-21

Melorheostosis is a very rare sclerosing bone disorder that involves frequently one limb. It may be asymptomatic, but pain and limb deformity may occur and can be very debilitating. Different reports have indicated efficacy of bisphosphonates (pamidronate and etidronate) on symptoms. We report an adult patient with a very painful melorheostosis, who  improved after treatment with zoledronate, either on symptoms or on bone scans.

Histological comparison of long-bone cortex between 11-year-old giant cow with dermal dysplasia and the child cow aged 8.5 years.

PubMed

Mori, Ryoichi; Kodaka, Tetsuo; Naito, Yoshihisa

2012-02-01

Young calves are known to be formed with laminar bone in long-bone cortex during growing periods and the osteon formation begins later. Previously, we reported that an 11-year-old giant Holstein cow with dermal dysplasia showed a delayed osteon formation. An 8.5-year-old cow, born from the giant Holstein cow, also showed some dermal dysplasia and the outer-half layer of the child almost retained laminar bone similar to that of the mother, although the body weight was approximately normal. The mother had formed the inner circumferential lamella and the child was going to form the inner circumferential lamella, but their outer circumferential lamellas were not formed yet in both of them, when compared with a 12-years-old cow as a control of the mother. Therefore, we suggest on long-bone formation pattern that the child resembled the mother rather than the control, and that the child had more or less succeeded to the mother genes of delayed osteon formation as well as dermal dysplasia which seemed to be genetic collagen disorder, although there were mild gene appearances.

Multiscale, Converging Defects of Macro-Porosity, Microstructure and Matrix Mineralization Impact Long Bone Fragility in NF1

PubMed Central

Kühnisch, Jirko; Seto, Jong; Lange, Claudia; Schrof, Susanne; Stumpp, Sabine; Kobus, Karolina; Grohmann, Julia; Kossler, Nadine; Varga, Peter; Osswald, Monika; Emmerich, Denise; Tinschert, Sigrid; Thielemann, Falk; Duda, Georg; Seifert, Wenke; el Khassawna, Thaqif; Stevenson, David A.; Elefteriou, Florent; Kornak, Uwe; Raum, Kay; Fratzl, Peter; Mundlos, Stefan; Kolanczyk, Mateusz

2014-01-01

Bone fragility due to osteopenia, osteoporosis or debilitating focal skeletal dysplasias is a frequent observation in the Mendelian disease Neurofibromatosis type 1 (NF1). To determine the mechanisms underlying bone fragility in NF1 we analyzed two conditional mouse models, Nf1Prx1 (limb knock-out) and Nf1Col1 (osteoblast specific knock-out), as well as cortical bone samples from individuals with NF1. We examined mouse bone tissue with micro-computed tomography, qualitative and quantitative histology, mechanical tensile analysis, small-angle X-ray scattering (SAXS), energy dispersive X-ray spectroscopy (EDX), and scanning acoustic microscopy (SAM). In cortical bone of Nf1Prx1 mice we detected ectopic blood vessels that were associated with diaphyseal mineralization defects. Defective mineral binding in the proximity of blood vessels was most likely due to impaired bone collagen formation, as these areas were completely devoid of acidic matrix proteins and contained thin collagen fibers. Additionally, we found significantly reduced mechanical strength of the bone material, which was partially caused by increased osteocyte volume. Consistent with these observations, bone samples from individuals with NF1 and tibial dysplasia showed increased osteocyte lacuna volume. Reduced mechanical properties were associated with diminished matrix stiffness, as determined by SAM. In line with these observations, bone tissue from individuals with NF1 and tibial dysplasia showed heterogeneous mineralization and reduced collagen fiber thickness and packaging. Collectively, the data indicate that bone fragility in NF1 tibial dysplasia is partly due to an increased osteocyte-related micro-porosity, hypomineralization, a generalized defect of organic matrix formation, exacerbated in the regions of tensional and bending force integration, and finally persistence of ectopic blood vessels associated with localized macro-porotic bone lesions. PMID:24465906

Tarsal Bone Dysplasia in Clubfoot as Measured by Ultrasonography: Can It be Used as a Prognostic Indicator in Congenital Idiopathic Clubfoot? A Prospective Observational Study.

PubMed

Chandrakanth, Udayakumar; Sudesh, Pebam; Gopinathan, NirmalRaj; Prakash, Mahesh; Goni, Vijay G

2016-01-01

Congenital talipes equinovarus (CTEV )/clubfoot is the most common congenital orthopedic condition. The success rate of Ponseti casting in the hands of the legend himself is not 100%. The prediction of difficult to correct foot and recurrences still remains a mystery to be solved. We all know that tarsal bones are dysplastic in clubfoot and considering it; we hypothesize that the amount of tarsal dysplasia can predict management duration and outcome. In literature we were not able to find studies that satisfactorily quantify the amount of tarsal dysplasia. Hence, it was considered worthwhile to quantify the amount of dysplasia in tarsal bone and to correlate these parameters with the duration and outcome of treatment by conventional method. A total of 25 infants with unilateral idiopathic clubfoot that have not taken any previous treatment were included in the study. An initial ultrasonography was done before start of treatment in 3 standard planes to measure the maximum length of 3 tarsal bones (talus, calcaneus, and navicular). Ponseti method of treatment was used; pirani scoring was done at each OPD (out patient department) visit. Number of casts required for complete correction and need for any surgical intervention were taken as the outcome parameters. We found that there is a significant correlation between number of casts required and the dysplasia of talus (α error=0.05). We also found a significant negative correlation between relative dysplasia of talus and number of casts required (r=-0.629 sig=0.001, r=-0.552 sig=0.004). Tarsal bone dysplasia as quantified by using ultrasonography can be used as a prognostic indicator in congenital idiopathic clubfoot. Although promising the method needs further studies and can be more useful after long-term follow-up where recurrences if any can be documented. Level II.

Cleidocranial dysplasia

PubMed Central

Dhiman, Neeraj Kumar; Singh, Akhilesh Kumar; Sharma, Naresh Kumar; Jaiswara, Chandresh

2014-01-01

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder resulting in the skeletal and dental abnormalities due to the disturbance in ossification of the bones. Clavicle is the most commonly affected bone. The prevalence of CCD is one in millions of live births. In this report, we present a case of 10-years-old boy showing features of this condition. PMID:25937737

Successful treatment of pain in melorheostosis with zoledronate, with improvement on bone scintigraphy

PubMed Central

Slimani, Samy; Nezzar, Adlen; Makhloufi, Hachemi

2013-01-01

Melorheostosis is a very rare sclerosing bone disorder that involves frequently one limb. It may be asymptomatic, but pain and limb deformity may occur and can be very debilitating. Different reports have indicated efficacy of bisphosphonates (pamidronate and etidronate) on symptoms. We report an adult patient with a very painful melorheostosis, who  improved after treatment with zoledronate, either on symptoms or on bone scans. PMID:23813581

Impact of endocrine hyperfunction and phosphate wasting on bone in McCune-Albright syndrome.

PubMed

Lala, R; Matarazzo, P; Andreo, M; Defilippi, C; de Sanctis, C

2002-01-01

Skin dysplasia, as café-au-lait spots, bone fibrous dysplasia and peripheral endocrinopathies are the main clinical features of McCune-Albright syndrome (MAS). This illness is due to activating mutations of the Gsalpha protein and is spread with a mosaic pattern in affected tissues that consist of intermixed areas of normal and mutated cells. Peripheral endocrine secretion, free of hypothalamic pituitary control, is the hallmark of the endocrine syndromes: precocious puberty, Cushing's syndrome, hyperthyroidism and gigantism/acromegaly. In addition, phosphate wasting as hyperphosphaturia is often present. The impact of hormonal hypersecretion and phosphate loss on the bones of patients with MAS is poorly understood both in normal and fibrous bone tissue. As hypercortisolism and hyperthyroidism increase bone resorption, hyperestrogenism and growth hormone hypersecretion stimulate bone growth and mineralization, and phosphate wasting reduces bone mineral content. All these actions can be exerted at varying times and degrees in a single patient on lesional and non-lesional bones. Sonographic evidence of multiple diffused hyperechogenic spots in the testes of patients with MAS do not seem to be related to alterations in calcium-phosphate metabolism but rather to zonal dysplasia/hyperplasia of testicular tissue.

Review of ectodermal dysplasia: case report on treatment planning and surgical management of oligodontia with implant restorations.

PubMed

Li, Dehua; Liu, Yanpu; Ma, Wei; Song, Yingliang

2011-10-01

Dental implants have proven to be a reliable modality for the rehabilitation of missing teeth. However, there are limited reports on managing anodontia related to ectodermal dysplasia in the scientific literature. The severely reduced bone quantity due to the congenital absence of multiple natural teeth is the biggest challenge for the surgeon. There are a variety of bone augmentation procedures to establish adequate bone quantity, and the surgical planning should be used on an individual case basis. This is a report of a 19-year-old male patient affected by hypohidrotic ectodermal dysplasia. Oligodontia associated with severe atrophy of jaws was the chief complaint for seeking treatment. Based on clinical and radiographic examinations, 2 bone augmentation procedures were used to obtain sufficient width of alveolus for implant placement by performing an onlay bone graft in the maxilla and vertical distraction osteogenesis in the mandible. The treatment planning was discussed and informed consent was obtained.

Maxillectomy for Cementifying Osseous Dysplasia of the Maxilla: A Case Report.

PubMed

Akbulut, Sevtap; Demir, Mehmet Gokhan; Basak, Kayhan; Paksoy, Mustafa

2015-01-01

Osseous dysplasias are the most common subtype of fibro-osseous lesions of the maxillofacial bones. They are benign and often present as incidental asymptomatic lesions. Diagnosis can be made with clinical and radiographic examination. This article reports the case of a 47-year-old man with a huge cementifying osseous dysplasia of the maxilla that presented with secondary infection after teeth extraction and repair of oroantral fistula. A subtotal maxillectomy had to be done after conservative treatment failed to resolve the infection. Biopsy, tooth extraction or surgical trauma to the affected bones of osseous dysplasia could easily lead to severe secondary infection, the treatment of which may be very difficult, and thus should be avoided if possible.

A giant cranial aneurysmal bone cyst associated with fibrous dysplasia.

PubMed

Składzieriń, J; Olés, K; Zagólski, O; Moskała, M; Sztuka, M; Strek, P; Wierzchowski, W; Tomik, J

2008-01-01

An aneurysmal bone cyst (ABC) is a rare, benign fibro-osseous lesion, considered a vascular phenomenon secondary to fibrous dysplasia or a giant-cell tumour, and occurs mainly in long bones and vertebrae. In this case report a 16-year-old male presented with massive epistaxis. He was admitted with a 3-year history of chronic rhinitis, headaches, right ocular pain and recurrent epistaxis. CT scans showed a predominantly cystic, expansive mass obstructing both nasal cavities, extending to all paranasal sinuses and both orbits, with evidence of anterior cranial fossa skull base destruction. The patient underwent a craniofacial resection of the tumour performed with an external approach and an immediate reconstruction of the dural defect. Histology confirmed the lesion was an ABC associated with fibrous dysplasia. The patient's recovery was complete. A large facial aneurysmal bone cyst can damage the facial skeleton and skull base, and requires excision by a combined external approach.

McCune Albright syndrome - association of fibrous dysplasia, café-au-lait skin spots and hyperthyroidism - case report.

PubMed

Raus, Iulian; Coroiu, Roxana Elena

2016-01-01

McCune-Albright syndrome is a rare sporadic disease characterized by bone fibrous dysplasia, café-au-lait skin spots and a variable association of hyperfunctional endocrine disorders. Fibrous dysplasia (FD), which can involve the craniofacial, axial, and appendicular skeleton, may range from an isolated, asymptomatic monostotic lesion to a severe disabling polyostotic disease involving the entire skeleton. A twenty-five-year old male patient presented to our clinic with recently developed heart palpitations. He had also been feeling pain in the right femur since he was younger, without any trauma history, leading to difficulties of ambulation and limping occasionally. His physical examination revealed café-au-lait spots with irregular borders and right testicular agenesis. Laboratory findings identified hyperthyroidism with hyperparathyroidism. Radiographs of the pelvis revealed multiple lytic lesions of the right femur and magnetic resonance imaging (MRI) characterized these lesions as specific to fibrous dysplasia of the bone, without any insufficiency fracture at this level. The association of café-au-lait skin spots with bone fibrous dysplasia, and hyperthyroidism in this patient suggested the diagnosis of McCune - Albright syndrome.

McCune Albright syndrome - association of fibrous dysplasia, café-au-lait skin spots and hyperthyroidism – case report

PubMed Central

RAUS, IULIAN; COROIU, ROXANA ELENA

2016-01-01

McCune–Albright syndrome is a rare sporadic disease characterized by bone fibrous dysplasia, café-au-lait skin spots and a variable association of hyperfunctional endocrine disorders. Fibrous dysplasia (FD), which can involve the craniofacial, axial, and appendicular skeleton, may range from an isolated, asymptomatic monostotic lesion to a severe disabling polyostotic disease involving the entire skeleton. A twenty-five-year old male patient presented to our clinic with recently developed heart palpitations. He had also been feeling pain in the right femur since he was younger, without any trauma history, leading to difficulties of ambulation and limping occasionally. His physical examination revealed café-au-lait spots with irregular borders and right testicular agenesis. Laboratory findings identified hyperthyroidism with hyperparathyroidism. Radiographs of the pelvis revealed multiple lytic lesions of the right femur and magnetic resonance imaging (MRI) characterized these lesions as specific to fibrous dysplasia of the bone, without any insufficiency fracture at this level. The association of café-au-lait skin spots with bone fibrous dysplasia, and hyperthyroidism in this patient suggested the diagnosis of McCune – Albright syndrome. PMID:27857528

Melorheostosis: clinicopathological features, diagnosis, and management.

PubMed

Jain, Vijay Kumar; Arya, Rajendra Kumar; Bharadwaj, Minakshi; Kumar, Satish

2009-07-01

Melorheostosis is a rare sclerosing bone disease. This article describes the histological patterns and radiographic characteristics commonly associated with melorheostosis. A paucity of compiled data about the disease in the literature necessitated a comprehensive review to further define its management.

Osteosclerotic bone dysplasia (melorheostosis) of the mandible.

PubMed

Kuttenberger, J J; Hardt, N; Gebbers, J-O; Hofer, B

2006-12-01

Melorheostosis is a linear bone dysplasia of unknown origin that may be associated with soft-tissue alterations. Although any part of the skeleton can be affected, this condition is rarely observed in the craniofacial region. Only seven cases of melorheostosis with craniofacial involvement have been reported and cranial manifestation only is even rarer. To the authors' knowledge, manifestation in the mandible only has not yet been documented. A patient with isolated melorheostosis of the mandible with characteristic symptomatic bone pain is presented. The clinical, radiological and histological findings are described and possible therapeutic options are discussed.

Pyle metaphyseal dysplasia in an African child: Case report and review of the literature.

PubMed

Wonkam, A; Makubalo, N; Roberts, T; Chetty, M

2016-05-25

Pyle disease (OMIM 265900), also known as metaphyseal dysplasia, is a rare autosomal recessive disorder with no known gene mutation. We report a case of Pyle disease in a 7-year-old African boy of mixed ancestry who presented with finger and wrist fractures following minor trauma. The radiological findings revealed abnormally broad metaphyses of the tubular bones, known as Erlenmeyer-flask bone deformity, and mild cranial sclerosis, both hallmarks of the condition. We report the first case in a patient with African ancestry, which could help in the gene discovery of this rare autosomal recessive skeletal dysplasia with unknown mutations.

A case of boomerang dysplasia with a novel causative mutation in filamin B: identification of typical imaging findings on ultrasonography and 3D-CT imaging.

PubMed

Tsutsumi, Seiji; Maekawa, Ayako; Obata, Miyuki; Morgan, Timothy; Robertson, Stephen P; Kurachi, Hirohisa

2012-01-01

Boomerang dysplasia is a rare lethal osteochondrodysplasia characterized by disorganized mineralization of the skeleton, leading to complete nonossification of some limb bones and vertebral elements, and a boomerang-like aspect to some of the long tubular bones. Like many short-limbed skeletal dysplasias with accompanying thoracic hypoplasia, the potential lethality of the phenotype can be difficult to ascertain prenatally. We report a case of boomerang dysplasia prenatally diagnosed by use of ultrasonography and 3D-CT imaging, and identified a novel mutation in the gene encoding the cytoskeletal protein filamin B (FLNB) postmortem. Findings that aided the radiological diagnosis of this condition in utero included absent ossification of two out of three long bones in each limb and elements of the vertebrae and a boomerang-like shape to the ulnae. The identified mutation is the third described for this disorder and is predicted to lead to amino acid substitution in the actin-binding domain of the filamin B molecule. Copyright © 2012 S. Karger AG, Basel.

Therapies for the bone in mucopolysaccharidoses

PubMed Central

Tomatsu, Shunji; Alméciga-Díaz, Carlos J.; Montaño, Adriana M.; Yabe, Hiromasa; Tanaka, Akemi; Dung, Vu Chi; Giugliani, Roberto; Kubaski, Francyne; Mason, Robert W.; Yasuda, Eriko; Sawamoto, Kazuki; Mackenzie, William; Suzuki, Yasuyuki; Orii, Kenji E.; Barrera, Luis A.; Sly, William S.; Orii, Tadao

2014-01-01

Patients with mucopolysaccharidoses (MPS) have accumulation of glycosaminoglycans in multiple tissues which may cause coarse facial features, mental retardation, recurrent ear and nose infections, inguinal and umbilical hernias, hepatosplenomegaly, and skeletal deformities. Clinical features related to bone lesions may include marked short stature, cervical stenosis, pectus carinatum, small lungs, joint rigidity (but laxity for MPS IV), kyphoscoliosis, lumbar gibbus, and genu valgum. Patients with MPS are often wheelchair-bound and physical handicaps increase with age as a result of progressive skeletal dysplasia, abnormal joint mobility, and osteoarthritis, leading to 1) stenosis of the upper cervical region, 2) restrictive small lung, 3) hip dysplasia, 4) restriction of joint movement, and 5) surgical complications. Patients often need multiple orthopedic procedures including cervical decompression and fusion, carpal tunnel release, hip reconstruction and replacement, and femoral or tibial osteotomy through their lifetime. Current measures to intervene in bone disease progression are not perfect and palliative, and improved therapies are urgently required. Enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), and gene therapy are available or in development for some types of MPS. Delivery of sufficient enzyme to bone, especially avascular cartilage, to prevent or ameliorate the devastating skeletal dysplasias remains an unmet challenge. The use of an anti-inflammatory drug is also under clinical study. Therapies should start at a very early stage prior to irreversible bone lesion, and damage since the severity of skeletal dysplasia is associated with level of activity during daily life. This review illustrates a current overview of therapies and their impact for bone lesions in MPS including ERT, HSCT, gene therapy, and anti-inflammatory drugs. PMID:25537451

The Radiograph of the Pelvis as a Window to Skeletal Dysplasias.

PubMed

Gajarajulu, Vijayalakshmi; Natarajan, Balakrishnan; Muralinath, S

2016-06-01

Skeletal dysplasias are disorders of bone formation. There are many dysplasias that have been identified and studied over the years and long lists of radiological features have been documented; it is not possible to remember all of them, most of which are common to more than one dysplasia. This article is about a practical approach to the radiological diagnosis of skeletal dysplasias by viewing only a few radiographs rather than the entire skeletal survey. The radiographs that are to be studied are AP view of the pelvis, dorsolumbar spine- AP and lateral view and both hands PA view, in that order. The skull lateral view and both knees AP view are sometimes required. The authors advice to set out with the pelvis that provides information of not only the pelvic bones but also parts of the lumbar spine and the upper ends of the femur including their epiphyses, metaphyses and a part of the diaphyses. Sometimes the diagnosis is reached with only this one radiograph, as in achondroplasia or it may indicate a group like mucopolysaccharidoses which can be sorted out with radiographs of the spine and hands or the upper part of the femur can provide a cue to epiphyseal and metaphyseal dysplasias. Gamuts and atlases can be consulted for the rare dysplasias.

An activating G{sub s}{alpha} mutation is present in fibrous dysplasia of bone in the McCune-Albright syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shenker, A.; Weinstein, L.S.; Spiegel, A.M.

1994-09-01

McCune-Albright syndrome (MAS) is a sporadic disease characterized by polyostotic fibrous dysplasia, cafe-au-lait spots, and multiple endocrinopathies. The etiology of fibrous dysplasia is unknown. Activating mutations of codon 201 in the gene encoding the {alpha}-subunit of G{sub s}, the G-protein that stimulates adenylyl cyclase, have been found in all affected MAS tissues that have been studied. Initial attempts to amplify DNA from decalcified paraffin-embedded bone specimens from frozen surgical bone specimens from five MAS patients using polymerase chain reaction and allele-specific oligonucleotide hybridization. Most of the cells in four specimens of dysplastic bone contained a heterozygous mutation encoding substitution ofmore » Arg{sup 201} of G{sub s}{alpha} with His, but the mutation was barely detectable in peripheral blood specimens from the patients. Only a small amount of mutant allele was detected in a specimen of normal cortical bone from the fifth patient, although this patients had a high proportion of mutation in other, affected tissues. The mosaic distribution of mutant alleles is consistent with an embryological somatic cell mutation of the G{sub s}{alpha} gene in MAS. The presence of an activating mutation of G{sub s}{alpha} in osteoblastic progenitor cells may cause them to exhibit increased proliferation and abnormal differentiation, thereby producing the lesions of fibrous dysplasia. 43 refs., 2 figs.« less

A novel FGFR3-binding peptide inhibits FGFR3 signaling and reverses the lethal phenotype of mice mimicking human thanatophoric dysplasia

PubMed Central

Jin, Min; Yu, Ying; Qi, Huabing; Xie, Yangli; Su, Nan; Wang, Xiaofeng; Tan, Qiaoyan; Luo, Fengtao; Zhu, Ying; Wang, Quan; Du, Xiaolan; Xian, Cory J.; Liu, Peng; Huang, Haiyang; Shen, Yue; Deng, Chu-Xia; Chen, Di; Chen, Lin

2012-01-01

Gain-of-function mutations in fibroblast growth factor receptor-3 (FGFR3) lead to several types of human skeletal dysplasia syndromes including achondroplasia, hypochondroplasia and thanatophoric dysplasia (TD). Currently, there are no effective treatments for these skeletal dysplasia diseases. In this study, we screened, using FGFR3 as a bait, a random 12-peptide phage library and obtained 23 positive clones that share identical amino acid sequences (VSPPLTLGQLLS), named as peptide P3. This peptide had high binding specificity to the extracellular domain of FGFR3. P3 inhibited tyrosine kinase activity of FGFR3 and its typical downstream molecules, extracellular signal-regulated kinase/mitogen-activated protein kinase. P3 also promoted proliferation and chondrogenic differentiation of cultured ATDC5 chondrogenic cells. In addition, P3 alleviated the bone growth retardation in bone rudiments from mice mimicking human thanatophoric dysplasia type II (TDII). Finally, P3 reversed the neonatal lethality of TDII mice. Thus, this study identifies a novel inhibitory peptide for FGFR3 signaling, which may serve as a potential therapeutic agent for the treatment of FGFR3-related skeletal dysplasia. PMID:23014564

Mesomelic skeletal dysplasias.

PubMed

Kaitila, I; Leisti, J T; Rimoin, D L

1976-01-01

Mesomelic shortening of the extremities lends itself as a useful clinical and/or radiologic sign to characterize a group of hereditary bone dysplasias. Table 1 and Figure 4 are presented to facilitate the comparison between the many different types of mesomelic dwarfism. Differential diagnosis between these types is not difficult because of the specific bone changes and extraskeletal malformations present. As in many hereditary syndromes, however, there may be wide clinical variability within a single entity, and meticulous clinical and radiologic examination must be done to arrive at the correct diagnosis. Certain other forms of chondrodystrophies, such as achondroplasia, hypochondroplasia, pseudoachondroplasia and distrophic dwarfism, can be easily differentiated from the mesomelic dysplasias by their clinical features and skeletal radiographs. Nothing is known about the pathogenesis of the various forms of mesomelic dysplasias. There is no available specific treatment, although corrective surgery has benefited selected patients. The correct diagnosis is, however, important both for prognostication and accurate genetic counseling.

Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies.

PubMed

Marie, Pierre J

2015-04-01

Several metabolic, genetic and oncogenic bone diseases are characterized by defective or excessive bone formation. These abnormalities are caused by dysfunctions in the commitment, differentiation or survival of cells of the osteoblast lineage. During the recent years, significant advances have been made in our understanding of the cellular and molecular mechanisms underlying the osteoblast dysfunctions in osteoporosis, skeletal dysplasias and primary bone tumors. This led to suggest novel therapeutic approaches to correct these abnormalities such as the modulation of WNT signaling, the pharmacological modulation of proteasome-mediated protein degradation, the induction of osteoprogenitor cell differentiation, the repression of cancer cell proliferation and the manipulation of epigenetic mechanisms. This article reviews our current understanding of the major cellular and molecular mechanisms inducing osteoblastic cell abnormalities in age-related bone loss, genetic skeletal dysplasias and primary bone tumors, and discusses emerging therapeutic strategies to counteract the osteoblast abnormalities in these disorders of bone formation.

Florid Cemento-Osseous Dysplasia Simultaneous the Chronic Suppurative Osteomyelitis in Mandible.

PubMed

Cavalcante, Mateus Barros; de Oliveira Lima, Amanda Laísa; Júnior, Marcus Antônio Brêda; Santos, Milkle Bruno Pessoa

2016-11-01

The florid cemento-osseous dysplasia is an uncommon condition nonneoplastic, of unknown cause with higher prevalence in melanodermic women, limited the maxillary bones, is characterized by the presence of dispersed and diffuse radiopaque calcifications, constituted of bone and dense cemento; however, when the bone is infected it induces the suppuration and formation of osseous sequestra, thus resulting in an osteomyelitis frame. The patient was attended in a Dental Specialties Center in the state of Alagoas, Brazil, presenting on clinical examination edema and extra oral fistula with pus drainage in hemiface submandibular of the right side. Radiographically it was possible to observe area of sclerosis and osseous sequestra involving the right side region of the mandible body, and it increases zones of the bone density. In association with clinical data and complementary diagnosis examinations, the option of treatment adopted was the complete removal of the bone fragment, followed by adaptation and plate fixation and titanium screws to reduce the risk of mandibular fracture. The aim of the present paper was to relate a clinical patient of florid cemento-osseous dysplasia simultaneous the chronic suppurative osteomyelitis, highlighting their clinical, radiographic, and histological characteristics, as well as their diagnosis and treatment.

Idiosyncratic Presentation of Cemento-Osseous Dysplasia - An in Depth Analysis Using Cone Beam Computed Tomography.

PubMed

Chennoju, Sai Kiran; Pachigolla, Ramaswamy; Govada, Vanya Mahitha; Alapati, Satish; Balla, Smitha

2016-05-01

Bone dysplasias comprise of a condition where the normal bone is replaced with fibrous tissue. Periapical Cemento-Osseous Dysplasia (PCOD) is a benign fibro-osseous condition where bone tissue is supplanted with fibrous tissue and cementum-like material. This condition affects mostly mandibular anterior region and rarely occurs in the maxilla. PCOD is seen above 30 years of age and has slight female predilection. Generally the teeth related to such lesions appear to be vital and are usually asymptomatic. These lesions are mostly seen during routine radiographic examination whose presentation may vary from complete radiolucency to dense radiopacity. The advent of Cone Beam Computed Tomography (CBCT) has brought a massive change in the field of dentistry which has become an important tool for diagnosis. Hence we hereby present an unusual case of cemento-osseous dysplasia in an unfamiliar location with an atypical presentation. The shape of the pathology was completely idiosyncratic and different from an orthodox lesion of COD, as the lesion was observed to grow out of the palatal surface with a prominent palatal expansion. This case highlights the importance of CBCT in radiographic diagnosis and in evaluating the characteristics of such lesion, which present with high diagnostic dilemma.

Partial double-layered patella in a nondysplasic adolescent.

PubMed

García-Mata, Serafín; Hidalgo-Ovejero, Angel

2016-11-01

Double-layered patella (DLP) is a rare patella-formation abnormality reported in association with multiple epiphyseal dysplasia. DLP is one of the five types of bipartite patella, caused by a coronal septum that divides the patella into anterior and posterior segments. Although the double layer of bone has been reported as complete, it may also manifest as partial, as in our case. A 13-year-old male patient attended A&E after accidentally falling and sustaining a direct injury to his left knee, with pain in the anterior surface of the right patella. He was diagnosed with an incomplete vertical fracture of the left patella. An axial view radiography indicated an external partial DLP. No bone dysplasia was found. Computed tomographic scan and MRI showed partial DLP and bone marrow oedema because of the injury in the femoral condyle, but no fracture. The reason for highlighting this type of patella abnormality is to present the case of a patient without bone dysplasia, either partial or incomplete, that has not been reported previously. We also wish to emphasize the importance of not confusing it with a fracture in standard radiographies.

Psychosocial reactions in the spouses of patients suffering polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy.

PubMed

Hakola, H P

1990-01-01

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLO-SL) is a rare hereditary disease affecting both brain and bones. Skeletal symptoms begin in early adulthood and neuropsychiatric symptoms at approximately age 30. Progressive dementia associated with an accentuated frontal lobe syndrome handicaps the patients. The author describes inadequate psychosocial reactions of the spouses of 21 Finnish PLO-SL patients. The reactions included rejection and divorce in 8 cases and rejection without divorce in 1 case. Jealousy, violence, and alcoholism were common in male spouses. The author suggests that some of the spouses' negative psychosocial reactions may be lessened if the family is informed early about the nature of the disorder.

New tumour entities in the 4th edition of the World Health Organization Classification of Head and Neck tumours: odontogenic and maxillofacial bone tumours.

PubMed

Speight, Paul M; Takata, Takashi

2018-03-01

The latest (4th) edition of the World Health Organization Classification of Head and Neck tumours has recently been published with a number of significant changes across all tumour sites. In particular, there has been a major attempt to simplify classifications and to use defining criteria which can be used globally in all situations, avoiding wherever possible the use of complex molecular techniques which may not be affordable or widely available. This review summarises the changes in Chapter 8: Odontogenic and maxillofacial bone lesions. The most significant change is the re-introduction of the classification of the odontogenic cysts, restoring this books status as the only text which classifies and defines the full range of lesions of the odontogenic tissues. The consensus group considered carefully the terminology of lesions and were concerned to ensure that the names used properly reflected the best evidence regarding the true nature of specific entities. For this reason, this new edition restores the odontogenic keratocyst and calcifying odontogenic cyst to the classification of odontogenic cysts and rejects the previous terminology (keratocystic odontogenic tumour and calcifying cystic odontogenic tumour) which were intended to suggest that they are true neoplasms. New entities which have been introduced include the sclerosing odontogenic carcinoma and primordial odontogenic tumour. In addition, some previously poorly defined lesions have been removed, including the ameloblastic fibrodentinoma, ameloblastic fibro-odontoma, which are probably developing odontomas, and the odontoameloblastoma, which is not regarded as an entity. Finally, the terminology "cemento" has been restored to cemento-ossifying fibroma and cemento-osseous dysplasias, to properly reflect that they are of odontogenic origin and are found in the tooth-bearing areas of the jaws.

Different clinical presentation and management of temporal bone fibrous dysplasia in children.

PubMed

Mierzwiński, Józef; Kosowska, Justyna; Tyra, Justyna; Haber, Karolina; Drela, Maria; Paczkowski, Dariusz; Burduk, Paweł

2018-01-15

Fibrous dysplasia is a slowly progressive benign fibro-osseous disorder that involves one or multiple bones with a unilateral distribution in most cases. It is a lesion of unknown etiology, uncertain pathogenesis, and diverse histopathology. Temporal bone involvement is the least frequently reported type, especially in children. We reviewed available articles regarding fibrous dysplasia with temporal bone involvement in children and added four patients aged 7 to 17 years who were diagnosed and treated in our institution from 2006 to 2017. The patients' clinical picture comprised head deformity, external canal stenosis, headache, progressive conductive and/or sensorineural hearing loss, tinnitus, and sudden deafness. Two patients had experienced severe episodic vertigo with nausea and vomiting. Two were referred to us with external canal obstruction and secondary cholesteatoma formation with broad middle ear destruction. One was diagnosed with acute mastoiditis and intracranial complications. Optimal management of fibrous dysplasia is unclear and can be challenging, especially in children. In our two patients with disease expansion and involvement of important structures, surgical treatment was abandoned and a "wait-and-scan" policy was applied. The other two were qualified for surgical treatment. One patient underwent two surgeries: modified lateral petrosectomy (canal left open) with pathological tissue removal, cavity obliteration, and subsequent tympanoplasty. Another patient with extensive destruction of the left temporal bone underwent canal wall down mastoidectomy with perisinus abscess drainage and revision 12 months later. Tympanoplasty was unsatisfactory in both patients because of slow progression of the middle ear pathology. None of our patients underwent pharmacological treatment. In younger patients, observation and a "wait-and-scan" protocol is relevant until significant function, or cosmetic deficits are obvious. Surgery is not preferred and should be delayed until puberty because fibrous dysplasia has a tendency to stabilize after adolescence. In patients with severe symptoms medical treatment can be implemented, but safety of this treatment in children remain controversial.

BK virus encephalopathy and sclerosing vasculopathy in a patient with hypohidrotic ectodermal dysplasia and immunodeficiency.

PubMed

Darbinyan, Armine; Major, Eugene O; Morgello, Susan; Holland, Steven; Ryschkewitsch, Caroline; Monaco, Maria Chiara; Naidich, Thomas P; Bederson, Joshua; Malaczynska, Joanna; Ye, Fei; Gordon, Ronald; Cunningham-Rundles, Charlotte; Fowkes, Mary; Tsankova, Nadejda M

2016-07-13

Human BK polyomavirus (BKV) is reactivated under conditions of immunosuppression leading most commonly to nephropathy or cystitis; its tropism for the brain is rare and poorly understood. We present a unique case of BKV-associated encephalopathy in a man with hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID) due to IKK-gamma (NEMO) mutation, who developed progressive neurological symptoms. Brain biopsy demonstrated polyomavirus infection of gray and white matter, with predominant involvement of cortex and distinct neuronal tropism, in addition to limited demyelination and oligodendroglial inclusions. Immunohistochemistry demonstrated polyoma T-antigen in neurons and glia, but expression of VP1 capsid protein only in glia. PCR analysis on both brain biopsy tissue and cerebrospinal fluid detected high levels of BKV DNA. Sequencing studies further identified novel BKV variant and disclosed unique rearrangements in the noncoding control region of the viral DNA (BKVN NCCR). Neuropathological analysis also demonstrated an unusual form of obliterative fibrosing vasculopathy in the subcortical white matter with abnormal lysosomal accumulations, possibly related to the patient's underlying ectodermal dysplasia. Our report provides the first neuropathological description of HED-ID due to NEMO mutation, and expands the diversity of neurological presentations of BKV infection in brain, underscoring the importance of its consideration in immunodeficient patients with unexplained encephalopathy. We also document novel BKVN NCCR rearrangements that may be associated with the unique neuronal tropism in this patient.

Managing Recurrence in Intraarticular Melorheostosis Involving the Knee Joint: A Case Report.

PubMed

John, Bobby; Sharma, Anirudh; Pandey, Ritesh A

2017-01-01

Melorheostosis is a rare benign sclerosing dysplasia affecting bone, which causes significant morbidity in the form of pain and restriction of joint movement. Treatment options are varied, and recurrence is common after surgical treatment. Choosing the most appropriate treatment option in the management of a recurrent case is challenging, with very little supporting evidence in literature owing to the rarity of the disease. We hereby present a case of recurrent melorheostosis involving the knee; discuss treatment options and the rationale of our treatment. We present the case of a 42-year-old female who was operated at our institution previously 7 years ago for melorheostosis of her left knee and had undergone excision of intrarticular hyperostotic masses. However, pain and limitation of motion recurred in the operated knee 4 years later, and radiographs and computed tomography revealed a mineralized mass situated behind the patella in the patellofemoral joint. She was treated with repeat open excision of the mass and put on a regimen of physiotherapy and bisphosphonates. Open excision of symptomatic hyperostotic or mineralized soft tissue masses is perhaps the favored treatment option in such cases, the other options being arthroscopic excision and total knee arthroplasty. Limited knee motion and size of the mass often make arthroscopy an unfeasible option. Total knee arthroplasty should be reserved for cases with significant flexion contractures of the knee, or where multiple excisions have failed.

Molecular, Phenotypic Aspects and Therapeutic Horizons of Rare Genetic Bone Disorders

PubMed Central

Dhawan, Naveen; Vohra, Shivani; Tu, Khin; Abdelmagid, Samir M.

2014-01-01

A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD) of the United States. Over 6,000 rare disorders affect approximately 1 in 10 Americans. Rare genetic bone disorders remain the major causes of disability in US patients. These rare bone disorders also represent a therapeutic challenge for clinicians, due to lack of understanding of underlying mechanisms. This systematic review explored current literature on therapeutic directions for the following rare genetic bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossificans progressiva, melorheostosis, multiple hereditary exostosis, osteogenesis imperfecta, craniometaphyseal dysplasia, achondroplasia, and hypophosphatasia. The disease mechanisms of Gorham-Stout disease, melorheostosis, and multiple hereditary exostosis are not fully elucidated. Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP. The use of bisphosphonates and IL-6 inhibitors has been explored to be useful in the treatment of fibrous dysplasia, but more research is warranted. Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed. There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities. PMID:25530967

Genetics Home Reference: diastrophic dysplasia

MedlinePlus

... Changes Diastrophic dysplasia is one of several skeletal disorders caused by mutations in the SLC26A2 gene. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue ...

Spondylo-meta-epiphyseal dysplasia (SMED), short limb-hand type: a congenital familial skeletal dysplasia with distinctive features and histopathology.

PubMed

Borochowitz, Z; Langer, L O; Gruber, H E; Lachman, R; Katznelson, M B; Rimoin, D L

1993-02-01

We report on a "new" severe short-limb bone dysplasia which can be labeled descriptively a spondylo-meta-epiphyseal dysplasia. The 3 patients were born to 2 unrelated Sepharadic Jewish families and a Puerto Rican family. Clinical abnormalities include small stature with short limbs including short hands, a short nose with wide nasal bridge and wide nostrils, a long philtrum, ocular hypertelorism, retro/micrognathia, and a narrow chest. Radiological abnormalities include platyspondyly, short tubular bones with very abnormal metaphyses and epiphyses beyond early infancy, short ribs, and a typical evolution of bony changes over time. Chondroosseous morphology and ultrastructure document sparse matrix and degenerating chondrocytes surrounded by dense amorphous material in the 1 patient studied. Consanguinity is present in 1 family. In addition to the described patient, 2 other short-limb sibs, who did not survive infancy, were born into this family. Even in the absence of any photographic or radiologic documentation of these other 2 infants, autosomal recessive mode of inheritance seems probable.

Fibrous Dysplasia of the Temporal Bone with External Auditory Canal Stenosis and Secondary Cholesteatoma.

PubMed

Liu, Yu-Hsi; Chang, Kuo-Ping

2016-04-01

Fibrous dysplasia is a slowly progressive benign fibro-osseous disease, rarely occurring in temporal bones. In these cases, most bony lesions developed from the bony part of the external auditory canals, causing otalgia, hearing impairment, otorrhea, and ear hygiene blockade and probably leading to secondary cholesteatoma. We presented the medical history of a 24-year-old woman with temporal monostotic fibrous dysplasia with secondary cholesteatoma. The initial presentation was unilateral conductive hearing loss. A hard external canal tumor contributing to canal stenosis and a near-absent tympanic membrane were found. Canaloplasty and type I tympanoplasty were performed, but the symptoms recurred after 5 years. She received canal wall down tympanomastoidectomy with ossciculoplasty at the second time, and secondary cholesteatoma in the middle ear was diagnosed. Fifteen years later, left otorrhea recurred again and transcanal endoscopic surgery was performed for middle ear clearance. Currently, revision surgeries provide a stable auditory condition, but her monostotic temporal fibrous dysplasia is still in place.

ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae.

PubMed

Elefteriou, Florent; Benson, M Douglas; Sowa, Hideaki; Starbuck, Michael; Liu, Xiuyun; Ron, David; Parada, Luis F; Karsenty, Gerard

2006-12-01

The transcription factor ATF4 enhances bone formation by favoring amino acid import and collagen synthesis in osteoblasts, a function requiring its phosphorylation by RSK2, the kinase inactivated in Coffin-Lowry Syndrome. Here, we show that in contrast, RSK2 activity, ATF4-dependent collagen synthesis, and bone formation are increased in mice lacking neurofibromin in osteoblasts (Nf1(ob)(-/-) mice). Independently of RSK2, ATF4 phosphorylation by PKA is enhanced in Nf1(ob)(-/-) mice, thereby increasing Rankl expression, osteoclast differentiation, and bone resorption. In agreement with ATF4 function in amino acid transport, a low-protein diet decreased bone protein synthesis and normalized bone formation and bone mass in Nf1(ob)(-/-) mice without affecting other organ weight, while a high-protein diet overcame Atf4(-/-) and Rsk2(-/-) mice developmental defects, perinatal lethality, and low bone mass. By showing that ATF4-dependent skeletal dysplasiae are treatable by dietary manipulations, this study reveals a molecular connection between nutrition and skeletal development.

Fibrous Dysplasia

MedlinePlus

... No. 15-7774 Last Reviewed 2015-06 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 ... your language or another language, contact the NIH Osteoporosis and Related Bone Diseases ~ National Resource Center at ...

Idiosyncratic Presentation of Cemento-Osseous Dysplasia – An in Depth Analysis Using Cone Beam Computed Tomography

PubMed Central

Pachigolla, Ramaswamy; Govada, Vanya Mahitha; Alapati, Satish; Balla, Smitha

2016-01-01

Bone dysplasias comprise of a condition where the normal bone is replaced with fibrous tissue. Periapical Cemento-Osseous Dysplasia (PCOD) is a benign fibro-osseous condition where bone tissue is supplanted with fibrous tissue and cementum-like material. This condition affects mostly mandibular anterior region and rarely occurs in the maxilla. PCOD is seen above 30 years of age and has slight female predilection. Generally the teeth related to such lesions appear to be vital and are usually asymptomatic. These lesions are mostly seen during routine radiographic examination whose presentation may vary from complete radiolucency to dense radiopacity. The advent of Cone Beam Computed Tomography (CBCT) has brought a massive change in the field of dentistry which has become an important tool for diagnosis. Hence we hereby present an unusual case of cemento-osseous dysplasia in an unfamiliar location with an atypical presentation. The shape of the pathology was completely idiosyncratic and different from an orthodox lesion of COD, as the lesion was observed to grow out of the palatal surface with a prominent palatal expansion. This case highlights the importance of CBCT in radiographic diagnosis and in evaluating the characteristics of such lesion, which present with high diagnostic dilemma. PMID:27437374

FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway

PubMed Central

Matsushita, Takehiko; Wilcox, William R.; Chan, Yuk Yu; Kawanami, Aya; Bükülmez, Hülya; Balmes, Gener; Krejci, Pavel; Mekikian, Pertchoui B.; Otani, Kazuyuki; Yamaura, Isakichi; Warman, Matthew L.; Givol, David; Murakami, Shunichi

2009-01-01

Activating mutations in FGFR3 cause achondroplasia and thanatophoric dysplasia, the most common human skeletal dysplasias. In these disorders, spinal canal and foramen magnum stenosis can cause serious neurologic complications. Here, we provide evidence that FGFR3 and MAPK signaling in chondrocytes promote synchondrosis closure and fusion of ossification centers. We observed premature synchondrosis closure in the spine and cranial base in human cases of homozygous achondroplasia and thanatophoric dysplasia as well as in mouse models of achondroplasia. In both species, premature synchondrosis closure was associated with increased bone formation. Chondrocyte-specific activation of Fgfr3 in mice induced premature synchondrosis closure and enhanced osteoblast differentiation around synchondroses. FGF signaling in chondrocytes increases Bmp ligand mRNA expression and decreases Bmp antagonist mRNA expression in a MAPK-dependent manner, suggesting a role for Bmp signaling in the increased bone formation. The enhanced bone formation would accelerate the fusion of ossification centers and limit the endochondral bone growth. Spinal canal and foramen magnum stenosis in heterozygous achondroplasia patients, therefore, may occur through premature synchondrosis closure. If this is the case, then any growth-promoting treatment for these complications of achondroplasia must precede the timing of the synchondrosis closure. PMID:18923003

Hyperostotic Esthesioneuroblastoma: Rare Variant and Fibrous Dysplasia Mimicker

PubMed Central

Knott, Phillip Daniel

2014-01-01

A 65-year-old male presented with a 3-year history of orbital symptoms. An imaging-based diagnosis of fibrous dysplasia involving the skull base was made at another institution. CT showed a diffuse sinonasal mass and ground-glass appearance of the bones of the anterior skull base with bony defects and mucocele formation. MRI demonstrated an accompanying intracranial and orbital rind of soft tissue mass along the hyperostotic bones. FDG-PET showed corresponding intense hypermetabolism. Small cysts were observed at the tumor-brain interface. Biopsy revealed esthesioneuroblastoma with bone infiltration that is compatible with the hyperostotic variant of esthesioneuroblastoma. There are a few cases of hyperostotic esthesioneuroblastoma reported in the literature. PMID:24497807

Neonatal Death Dwarfism in a Girl with Distinctive Bone Dysplasia Compatible with Grebe Chondrodysplasia: Analysis by CT Scan-based Phenotype.

PubMed

Al Kaissi, Ali; Chehida, Farid Ben; Ganger, Rudolf; Grill, Franz

2014-01-01

We report on a female fetus noted to have severe malformative type of skeletal dysplasia on ultrasonography done at 35 weeks gestation. The girl died shortly after birth. Clinical examination showed a fetus with severe dwarfism, extensive long and short bones, and bone deficiencies associated with multiple dislocations. Computed tomography (CT) scan-based phenotype showed a complex constellation of malformations consistent with the diagnosis of Grebe syndrome. Parents being first cousins (consanguineous marriage) strongly suggests autosomal recessive pattern of inheritance. To our knowledge, this is the first report of neonatal death dwarfism of Grebe syndrome analyzed by CT scan-based phenotype.

Unusual fan shaped ossification in a female fetus with radiological features of boomerang dysplasia

PubMed Central

Odent, S.; Loget, P.; Le Marec, B.; Delezoide, A.; Maroteaux, P.

1999-01-01

We report on a female fetus of 24 weeks whose clinical and radiological findings were compatible with boomerang dysplasia (BD). However, histopathology was unusual with a lateral fan shaped diaphyseal ossification. This has never been described either in typical atelosteogenesis I (AT-I) or in BD. The purpose of this report is to find out if this condition is a separate lethal bone dysplasia or another histological feature of the nosological group of AT-I and BD. 


Keywords: boomerang dysplasia; atelosteogenesis; lethal chondrodysplasia; lethal dwarfism PMID:10227404

Mondini dysplasia with recurrent bacterial meningitis caused by three different pathogens.

PubMed

Shikano, Hiroaki; Ohnishi, Hidenori; Fukutomi, Hisashi; Ito, Kimiko; Morimoto, Masahiro; Teramoto, Takahide; Aoki, Mitsuhiro; Nishihori, Takezumi; Akeda, Yukihiro; Oishi, Kazunori; Fukao, Toshiyuki

2015-12-01

Mondini dysplasia is rare, but has an important association with recurrent bacterial meningitis. We herein describe the case of a 3-year-old girl with unilateral sensorineural hearing loss who presented with three independent episodes of bacterial meningitis within 8 months. Temporal bone computed tomography indicated the characteristic features of Mondini dysplasia in the right inner ear. This was treated by surgical closure of the inner ear defect via oval window and additional vaccination was administered. Appropriate vaccination might prevent the recurrent bacterial meningitis associated with Mondini dysplasia. © 2015 Japan Pediatric Society.

[Multiple long bone fractures in a child with pycnodysostosis. A case report].

PubMed

Rojas, Paula I; Niklitschek, Nathia E; Sepúlveda, Matías F

2016-06-01

Fractures are an important entity to consider in pediatric patients. There are certain diseases in which bones fracture with a minimal trauma. Pycnodysostosis is an autosomal recessive unusual type of cráneo metaphyseal dysplasia, that presents frequently as fracture in a pathological bone. A 9 year old caucasian female, diagnosed with pycnodysostosis, was admitted with a right femur fracture as a result of a low energy trauma. Radiographic studies showed bilateral femur fractures, proximal fracture and non-union in antecurvatum of the left tibia. Pycnodysostosis is a rare disease, generally diagnosed at an early age by growth restriction, frequent fractures or fractures with low energy trauma. Therapy alternatives are limited, and no permanent cure has been developed. If a patient has dysmorphic facial features and fractures in a pathological bone, it is important to suspect bone dysplasia, such as pycnodysostosis and its differential diagnoses. Sociedad Argentina de Pediatría.

A possible case of Garre's sclerosing osteomyelitis from Medieval Tuscany (11th-12th centuries).

PubMed

Giuffra, Valentina; Vitiello, Angelica; Giusiani, Sara; Caramella, Davide; Fornaciari, Gino

2015-12-01

Archaeological excavations carried out at the castle of Monte di Croce near Florence brought to light a small cemetery complex belonging to the castle church, dated back to the 11th-12th centuries. An elite stone tomb contained the skeletal remains of a male aged 35-45 years with obvious pathology of the right tibia. The proximal metaphysis and the upper half of the diaphysis appear massively enlarged as a result of severe chronic periostitis. A transverse section illustrates complete obliteration of the medullary cavity by new spongy bone, with some large cavitations. The primary, but completely remodeled tibial shaft is still recognizable. This finding and the strong sclerotic reaction with some central cavitations rule out any form of bone tumor and indicate a chronic inflammatory disease. The morphological and radiological picture and the tibial localization suggest a diagnosis of chronic sclerosing osteomyelitis of Garré, a rare form of chronic osteomyelitis characterized by an intense periosteal reaction with little or no suppuration. Copyright © 2015. Published by Elsevier Inc.

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory.

PubMed

Jones, W; Roberts, R E

1933-05-01

(1) Pathology of calcification and ossification.-The Leriche-Policard theories. Hyperaemia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. "Myositis ossificans."(2) Radiological significance of density of bone shadows.-Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular.(3) Hyperaemic decalcification of bone.-Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperaemic dislocation of the atlas. Hyperaemic decalcification and nephrolithiasis.(4) Anaemic sclerosis of bone.-Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone-Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases.(5) Pathological calcification.-Calcification of supraspinatus tendon. Calcification of tumours-angioma, haematoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs.(6) Pathological ossification.-Ossification of tendons. Ossification of semilunar cartilages.

Concomitant occurrence of cochleosaccular dysplasia and Down's syndrome.

PubMed

Walby, A P; Schuknecht, H F

1984-07-01

Inherited cochleosaccular dysplasia occurred in a woman coincidentally with Down's syndrome. Study of the right temporal bone revealed abnormalities of the cochlea and saccule consistent with Scheibe 's original description. There was also a short cochlea and small lateral semicircular canal consistent with previous descriptions of Down's syndrome.

Genetics Home Reference: gnathodiaphyseal dysplasia

MedlinePlus

... can result in deterioration of the exposed bone (osteonecrosis of the jaw). Also, normal bone in areas ... Institute of Arthritis and Musculoskeletal and Skin Diseases: Osteonecrosis Educational Resources (4 links) American College of Rheumatology: ...

CBCT findings of periapical cemento-osseous dysplasia: A case report.

PubMed

Eskandarloo, Amir; Yousefi, Faezeh

2013-09-01

Periapical cemento-osseous dysplasia (PCOD) is a subtype of cemento-osseous dysplasia that usually occurs in middle-aged black women. This report described a case of a 45-year-old Iranian woman who was diagnosed with PCOD on the basis of cone beam computed tomographic (CBCT) findings. CBCT enabled detailed visualization of the bone changes. This report described the special radiographic characteristics of PCOD, including discontinuity of the lingual cortex on the CBCT sectional and three-dimensional images.

CBCT findings of periapical cemento-osseous dysplasia: A case report

PubMed Central

Eskandarloo, Amir

2013-01-01

Periapical cemento-osseous dysplasia (PCOD) is a subtype of cemento-osseous dysplasia that usually occurs in middle-aged black women. This report described a case of a 45-year-old Iranian woman who was diagnosed with PCOD on the basis of cone beam computed tomographic (CBCT) findings. CBCT enabled detailed visualization of the bone changes. This report described the special radiographic characteristics of PCOD, including discontinuity of the lingual cortex on the CBCT sectional and three-dimensional images. PMID:24083217

New Lethal Skeletal Dysplasia with Dandy-Walker Malformation, Congenital Heart Defects, Abnormal Thumbs, Hypoplastic Genitalia, and Distinctive Facies

PubMed Central

Stevens, Cathy A.; Lachman, Ralph S.

2011-01-01

We report on two sibs with a lethal form of bone dysplasia with distinctive skeletal findings including rhizomelic and mesomelic limb shortening, hooked clavicles, dumbbell femurs, and absence of talus and calcaneus ossification. Other clinical features include Dandy-Walker malformation, congenital heart defects, joint contractures, genital hypoplasia, and distinctive facial features. These sibs appear to have a previously undescribed skeletal dysplasia, which is most likely inherited in an autosomal recessive fashion. PMID:20602491

Prosthodontic rehabilitation in patient with ectodermal dysplasia combining preprosthetic techniques: a case report.

PubMed

Pombo Castro, María; Luaces Rey, Ramón; Arenaz Búa, Jorge; Santana-Mora, Urbano; López-Cedrún Cembranos, José Luís

2013-10-01

Oral manifestations in ectodermal dysplasia include oligodontia, alveolar ridges hypoplasia, and others. Due to the special conditions in terms of unhealthy teeth and lack of bone, implant-supported rehabilitation seems to offer the most satisfactory outcome. A 27-year-old male diagnosed with ectodermal dysplasia was referred to our department for oral rehabilitation. Oral manifestations included oligodontia, maxillary and mandibular atrophy, mandibular alveolar ridge with knife-edge morphology, and conical teeth. Treatment planning consisted of a Le Fort I osteotomy with interpositional grafts, bilateral sinus lift, and placement of maxillary and mandibular inlay and onlay corticocancellous grafts, using autologous iliac crest bone. In the second surgery, all remaining teeth were removed and 11 endosteal implants were placed. Six months after implant placement, a bimaxillary fixed implant-supported prosthesis was delivered, maintaining a satisfactory esthetic and functional result after a 2-year follow-up. The use of combined preprosthetic techniques allows the placement of endosteal implants and a fixed implant-supported prosthesis in patients with oligodontia and ectodermal dysplasia, providing an esthetic and functional oral rehabilitation.

ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae

PubMed Central

Elefteriou, Florent; Benson, M. Douglas; Sowa, Hideaki; Starbuck, Michael; Liu, Xiuyun; Ron, David; Parada, Luis F.; Karsenty, Gerard

2009-01-01

Summary The transcription factor ATF4 enhances bone formation by favoring amino acid import and collagen synthesis in osteoblasts, a function requiring its phosphorylation by RSK2, the kinase inactivated in Coffin-Lowry Syndrome. Here, we show that in contrast, RSK2 activity, ATF4-dependent collagen synthesis, and bone formation are increased in mice lacking neurofibromin in osteoblasts (Nf1ob−/− mice). Independently of RSK2, ATF4 phosphorylation by PKA is enhanced in Nf1ob−/− mice, thereby increasing Rankl expression, osteoclast differentiation, and bone resorption. In agreement with ATF4 function in amino acid transport, a low-protein diet decreased bone protein synthesis and normalized bone formation and bone mass in Nf1ob−/− mice without affecting other organ weight, while a high-protein diet overcame Atf4−/− and Rsk2−/− mice developmental defects, perinatal lethality, and low bone mass. By showing that ATF4-dependent skeletal dysplasiae are treatable by dietary manipulations, this study reveals a molecular connection between nutrition and skeletal development. PMID:17141628

Present status of the use of growth hormone in short children with bone diseases (diseases of the skeleton).

PubMed

Kanaka-Gantenbein, C

2001-01-01

Skeletal dysplasias are genetic disorders of bone and cartilage development, mainly characterized by disproportionate short stature. Achondroplasia is the commonest and best described form of skeletal dysplasia, leading to a mean final height of 131+/-5.6 cm for males and 124+/-5.9 cm for females. Growth hormone (GH) has been used in different studies in patients with achondroplasia in order to ameliorate their height, and short term results range from rather positive to moderate. However, disproportionate advancement of bone age has been observed that can compromise the positive effect of such treatment. Furthermore, concern exists about the aggravation of body disproportion necessitating a later leg lengthening procedure in order to achieve proportionate adult stature. In hypochondroplasia, GH treatment seems to give better results when administered at puberty. No data on final height yet exist, however, so that more studies with greater numbers of patients need to be performed before a consensus on GH use in achondroplasia and hypochondroplasia can be reached. Other forms of skeletal dysplasias are quite rare, so that no conclusion on GH use in such patients can be drawn. Finally, in osteogenesis imperfecta, GH administration significantly ameliorates bone density but does not clearly seem to affect final height positively.

Associated aneurysmal bone cyst and cemento-osseous dysplasia: a case report and review of the literature.

PubMed

Jacomacci, Willian Pecin; Veloso Perdigão, João Paulo; Veltrini, Vanessa Cristina; Farah, Gustavo Jacobucci; Tolentino, Elen Souza; Vessoni Iwaki, Lilian Cristina; Iwaki Filho, Liogi

2017-01-01

The purpose of this case report is to describe a previously unpublished association between focal cemento-osseous dysplasia (FCOD) and an aneurysmal bone cyst (ABC) and review the literature with regard to associated benign fibro-osseous lesions and cysts. A 41-year-old woman without a history of trauma presented with asymptomatic swelling in the right side of the mandible. Radiographs of the region revealed a unilocular radiolucent area with radiopaque foci. After aspiration of the lesion was positive for serosanguineous fluid, complete excision of the lesion was performed. Microscopic examination revealed a hybrid ABC and FCOD. The 12-month follow-up showed significant bone repair and no signs of recurrence. A review of the English-language literature from 1980 to 2012 revealed 1 retrospective study, 4 case series, and 18 single-case reports on the topic of cemento-osseous dysplasias, fibro-osseous lesions, and aneurysmal bone cysts. Of 59 cases, none reported an association between an ABC and FCOD. Although fibro-osseous lesions do not require intervention, surgical excision is recommended when they are associated with cysts. This case, in which an ABC and FCOD were associated, reinforces the need for a careful diagnostic process in radiographically mixed lesions that respond positively to aspiration biopsy.

Managing Recurrence in Intraarticular Melorheostosis Involving the Knee Joint: A Case Report

PubMed Central

John, Bobby; Sharma, Anirudh; Pandey, Ritesh A

2017-01-01

Introduction: Melorheostosis is a rare benign sclerosing dysplasia affecting bone, which causes significant morbidity in the form of pain and restriction of joint movement. Treatment options are varied, and recurrence is common after surgical treatment. Choosing the most appropriate treatment option in the management of a recurrent case is challenging, with very little supporting evidence in literature owing to the rarity of the disease. We hereby present a case of recurrent melorheostosis involving the knee; discuss treatment options and the rationale of our treatment. Case Report: We present the case of a 42-year-old female who was operated at our institution previously 7 years ago for melorheostosis of her left knee and had undergone excision of intrarticular hyperostotic masses. However, pain and limitation of motion recurred in the operated knee 4 years later, and radiographs and computed tomography revealed a mineralized mass situated behind the patella in the patellofemoral joint. She was treated with repeat open excision of the mass and put on a regimen of physiotherapy and bisphosphonates. Conclusion: Open excision of symptomatic hyperostotic or mineralized soft tissue masses is perhaps the favored treatment option in such cases, the other options being arthroscopic excision and total knee arthroplasty. Limited knee motion and size of the mass often make arthroscopy an unfeasible option. Total knee arthroplasty should be reserved for cases with significant flexion contractures of the knee, or where multiple excisions have failed. PMID:29242791

Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis of 16 observational studies.

PubMed

Zheng, Han-Han; Jiang, Xue-Liang

2016-04-01

Ulcerative colitis (UC) patients with concomitant primary sclerosing cholangitis (PSC) carry an increased risk of colorectal neoplasia (dysplasia and cancer), whereas the association between PSC and the development of colorectal neoplasia in Crohn's disease (CD) is controversial. A meta-analysis was carried out to compare the risk of this neoplasia in patients with inflammatory bowel disease (IBD) with and without PSC. A systematic research of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials was performed to identify studies that compared the risk of colorectal neoplasia (dysplasia and cancer) in patients with IBD with and without PSC. Quality assessment was performed using the Newcastle-Ottawa Scale. Pooled odds ratio (OR) was calculated using the random-effects model by STATA 12.0. A total of 16 studies (four cohort studies, 12 case-control studies; nine prospective studies and seven retrospective studies) were selected for further study. These studies included 13 379 IBD patients, of whom 1022 also had PSC. Patients with IBD and PSC were at an increased risk of colorectal dysplasia and cancer compared with patients with IBD alone [OR 3.24; 95% confidence interval (CI): 2.14-4.90]. This increased risk was present even when the risk of colorectal cancer alone was analysed (OR 3.41; 95% CI: 2.13-5.48). Data only from patients with UC showed that PSC was associated with an increased risk for the development of colorectal neoplasia and cancer in patients with UC (OR 2.98; 95% CI: 1.54-5.76) (OR 3.01; 95% CI: 1.44-6.29), but there were high heterogeneity among studies (I=76.9 and 62.8%, respectively). Heterogeneity of the studies was affected by the study design (prospective or retrospective). The OR of colorectal neoplasia was 2.32 (95% CI: 0.70-7.70, P=0.133) and that of cancer was 2.91 (95% CI: 0.84-10.16, P=0.388) for patients with CD and concurrent PSC. Patients with IBD and PSC have a markedly higher risk for the development of colorectal neoplasia than patients with IBD, but not PSC. Stratification by IBD type show that the presence of PSC is associated with an increased risk for the development of colorectal neoplasia in patients with UC; however, there is a nonsignificant association in CD patients. When the risk of colorectal cancer alone is analysed, the conclusion does not change.

DNA Methylation and Mutation of Small Colonic Neoplasms in Ulcerative Colitis and Crohn's Colitis: Implications for Surveillance.

PubMed

Johnson, David H; Taylor, William R; Aboelsoud, Mohammed M; Foote, Patrick H; Yab, Tracy C; Cao, Xiaoming; Smyrk, Thomas C; Loftus, Edward V; Mahoney, Douglas W; Ahlquist, David A; Kisiel, John B

2016-07-01

Stool DNA testing in patients with inflammatory bowel disease (IBD) may detect colorectal cancer and advanced precancers with high sensitivity; less is known about the presence of DNA markers in small IBD lesions, their association with metachronous neoplasia, or contribution to stool test positivity. At a single center in 2 blinded phases, we assayed methylated bone morphogenic protein 3, methylated N-Myc downstream-regulated gene 4, and mutant KRAS in DNA extracted from paraffin-embedded benign lesions, and matched control tissues of patients with IBD, who were followed for subsequent colorectal dysplasia. Stool samples from independent cases and controls with lesions <1 cm or advanced neoplasms were assayed for the same markers. Among IBD lesions (29 low-grade dysplasia, 19 serrated epithelial change, and 10 sessile serrated adenoma/polyps), the prevalence of methylation was significantly higher than in mucosae from 44 matched IBD controls (P < 0.0001 for methylated bone morphogenic protein 3 or methylated N-Myc downstream-regulated gene 4). KRAS mutations were more abundant in serrated epithelial change than all other groups (P < 0.001). Subsequent dysplasia was not associated with DNA marker levels. In stools, the sensitivity of methylated bone morphogenic protein 3 as a single marker was 60% for all lesions <1 cm, 63% for low-grade dysplasia ≥1 cm and 81% for high-grade dysplasia/colorectal cancer, all at 91% specificity (P < 0.0001). Selected DNA markers known to be present in advanced IBD neoplasia can also be detected in both tissues and stools from IBD patients with small adenomas and serrated lesions. Mutant KRAS exfoliated from serrated epithelial change lesions might raise false-positive rates. These findings have relevance to potential future applications of stool DNA testing for IBD surveillance.

Radiographic Underestimation of In Vivo Cup Coverage Provided by Total Hip Arthroplasty for Dysplasia.

PubMed

Nie, Yong; Wang, HaoYang; Huang, ZeYu; Shen, Bin; Kraus, Virginia Byers; Zhou, Zongke

2018-01-01

The accuracy of using 2-dimensional anteroposterior pelvic radiography to assess acetabular cup coverage among patients with developmental dysplasia of the hip after total hip arthroplasty (THA) remains unclear in retrospective clinical studies. A group of 20 patients with developmental dysplasia of the hip (20 hips) underwent cementless THA. During surgery but after acetabular reconstruction, bone wax was pressed onto the uncovered surface of the acetabular cup. A surface model of the bone wax was generated with 3-dimensional scanning. The percentage of the acetabular cup that was covered by intact host acetabular bone in vivo was calculated with modeling software. Acetabular cup coverage also was determined from a postoperative supine anteroposterior pelvic radiograph. The height of the hip center (distance from the center of the femoral head perpendicular to the inter-teardrop line) also was determined from radiographs. Radiographic cup coverage was a mean of 6.93% (SD, 2.47%) lower than in vivo cup coverage for these 20 patients with developmental dysplasia of the hip (P<.001). However, both methods yielded highly correlated measurements for cup coverage (Pearson r=0.761, P<.001). The size of the acetabular cup (P=.001) but not the position of the hip center (high vs normal) was significantly associated with the difference between radiographic and in vivo cup coverage. Two-dimensional radiographically determined cup coverage conservatively reflects in vivo cup coverage and remains an important index (taking 7% underestimation errors and the effect of greater underestimation of larger cup size into account) for assessing the stability of the cup and monitoring for adequate ingrowth of bone. [Orthopedics. 2018; 41(1):e46-e51.]. Copyright 2017, SLACK Incorporated.

Neonatal cholestasis and focal medullary dysplasia of the kidneys in a case of microcephalic osteodysplastic primordial dwarfism.

PubMed Central

Berger, A; Haschke, N; Kohlhauser, C; Amman, G; Unterberger, U; Weninger, M

1998-01-01

We report on a male infant who presented with intrauterine growth retardation, severe postnatal failure to thrive, microcephaly, facial dysmorphism, and skeletal dysplasia. The clinical and radiological findings are consistent with former descriptions of microcephalic osteodysplastic primordial dwarfism (MOPD) type I/III. In addition to previously published features, multiple fractures of the long bones, severe neonatal cholestasis, and histological dysplasia of the kidneys were found. The boy died at the age of 8 months. The new finding of focal renal medullary dysplasia further supports the hypothesis of a basic defect in tissue differentiation in the pathogenesis of this rare condition. Images PMID:9475098

[Clinical and molecular study in a family with cleidocranial dysplasia].

PubMed

Callea, Michele; Fattori, Fabiana; Bertini, Enrico S; Yavuz, Izzet; Bellacchio, Emanuele; Avendaño, Andrea; Araque, Dianora; Lacruz-Rengel, María A; Da Silva, Gloria; Cammarata-Scalisi, Francisco

2017-12-01

Cleidocranial dysplasia is an uncommon bone dysplasia with an autosomal dominant inheritance pattern characterized by short stature, large fontanels, midface hypoplasia, absence or hypoplasia of clavicles and orodental alterations. This is Estudio clínico y molecular en una familia con displasia cleidocraneal Clinical and molecular study in a family with cleidocranial dysplasia produced by mutations in the RUNX2 gene located at 6p21.1. We report two male adolescents (cousins), with cleidocranial dysplasia who presented a heterozygous missense mutation (c.674G> A, p.R225Q) in the RUNX2 gene, characterized by severe phenotype, such as absent clavicles, but with variation in the delayed fontanel closure, dental abnormalities (anomalies in shape and number) and scoliosis, thus demonstrating intrafamilial variation in these patients with the same genotype. Sociedad Argentina de Pediatría.

Detection of melorheostosis in a young lady with upper limb pain on Three Phase Bone Scintigram/SPECT-CT.

PubMed

Hassan, Aamna; Khalid, Madeeha; Khawar, Saquib

2016-01-01

Melorheostosis is a benign, noninheritable bone dysplasia characterized by its classic radiographic features of dense, flowing hyperostosis. It frequently affects one limb, usually the lower extremity and rarely the axial skeleton. A 26-year-old lady with obesity, polycystic ovarian syndrome and scalp dandruff presented with a long standing history of upper extremity pain and inability to adduct the arm completely. A Tc-99m MDP whole body and SPECT/CT scan performed for suspected fibrous dysplasia showed increased radiotracer uptake in densely sclerotic humeral and radial melorheostosis. This case highlighted the role of SPECT/CT imaging in this rare condition.

Focal cemento-osseous dysplasia of mandible

PubMed Central

Cankaya, Abdülkadir Burak; Erdem, Mehmet Ali; Olgac, Vakur; Firat, Deniz Refia

2012-01-01

Fibro-osseous lesions are disturbances in bone metabolism in which normal bone is replaced by a connective tissue matrix that then gradually develops into cemento-osseous tissue. Typically, the lesion is asymptomatic and is detected on routine radiographic examination. Radiologically, this lesion has three stages of maturation: pure radiolucent, radiopaque/mixed radiolucent, and radiopaque appearance. During these stages the lesion can be misdiagnosed. In this case report a 69-year- old patient with a a complaint of painless swelling of the left mandibular molar and premolar area is presented along with a review of the differential diagnoses considered in order to reach a final diagnosis of focal cemento-osseous dysplasia. PMID:22948991

Focal cemento-osseous dysplasia of mandible.

PubMed

Cankaya, Abdülkadir Burak; Erdem, Mehmet Ali; Olgac, Vakur; Firat, Deniz Refia

2012-09-03

Fibro-osseous lesions are disturbances in bone metabolism in which normal bone is replaced by a connective tissue matrix that then gradually develops into cemento-osseous tissue. Typically, the lesion is asymptomatic and is detected on routine radiographic examination. Radiologically, this lesion has three stages of maturation: pure radiolucent, radiopaque/mixed radiolucent, and radiopaque appearance. During these stages the lesion can be misdiagnosed. In this case report a 69-year- old patient with a a complaint of painless swelling of the left mandibular molar and premolar area is presented along with a review of the differential diagnoses considered in order to reach a final diagnosis of focal cemento-osseous dysplasia.

Rare, simultaneous, multiple, and recurrent mandibular bone cysts.

PubMed

Mupparapu, Muralidhar; Milles, Maano; Singer, Steven R; Rinaggio, Joseph

2008-04-01

Simple bone cysts, also referred to as traumatic bone cysts, are benign connective tissue-lined cavities occurring most commonly in young people. Most of the time, they occur as solitary radiolucencies. In the jaws, they also have been reported to occur concurrently with benign fibro-osseous lesions. The radiographic appearance of simple bone cysts could be confused with other jaw cysts and benign tumors. This case report presents a patient who had 3 separate lesions simultaneously within the mandible. The right mandibular lesion presented as a multilocular radiolucency. The 2 left mandibular lesions were periapical, with mixed radiodensities and radiographically mimicked lesions of focal or periapical cemento-osseous dysplasia. More aggressive benign lesions of the jaw were initially included in the differential diagnosis, as well. A biopsy revealed the diagnosis of simple bone cysts in all 3 locations. Minimal surgical management resulted in complete recovery of these osseous defects only to recur in 2 years on the mandibular left premolar-molar region. A new biopsy confirmed that the lesion was a recurrent simple bone cyst. Simultaneous presence of benign cemento-osseous dysplasia was also considered, as it is known to coexist with the simple bone cysts.

Clinical outcomes of implant therapy in ectodermal dysplasia patients: a systematic review.

PubMed

Wang, Y; He, J; Decker, A M; Hu, J C; Zou, D

2016-08-01

The purpose of this review was to determine the outcome of oral function reconstruction in ectodermal dysplasia (ED) patients who have received dental implant therapy. A search was made of the PubMed and Web of Science databases; key words used were "(ectodermal dysplasia) AND (implant OR implants)", with supplementary retrieval key words "dental implant", "zygomatic implant", "anodontia", and "edentulous". Patient age, use of bone graft, implant site, type of implant, and survival rate of the implants were included in the subsequent data analysis. Forty-five articles published between 1988 and October 2015 were included in this analysis. The cases of a total of 96 patients were retrieved (22 children and 74 adults); these patients received a total of 701 implants. Fourteen implants were removed during a median follow-up time of 24 months. The 24-month implant survival rate was 97.9% in adult subjects and 98.6% in children. Sixty-eight percent of adult patients underwent bone augmentation prior to implant placement. Based on this review, dental implants are commonly used in the oral reconstruction of ED patients. However, long-term data on bone augmentation and implant success are needed, as well as additional clinical evidence on bone resorption, the esthetic outcomes of implant therapy, and physiological considerations in ED patients. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Chondroblastoma with Secondary Aneurysmal Bone Cyst

DTIC Science & Technology

2008-02-01

dysplasia, chondroblastoma, chondromyxoid fibroma, osteochondroma, giant cell tumors, or enchondroma. Chondrosarcoma , osteoblastoma–aggressive variant and...Histology reveals cartilage with a layer of smooth, thin bone surrounding. 2 Chondrosarcomas tend to occur in an older population than most primary bone...mentioned was considered. All of those suspected neoplasms, with the exception of chondrosarcoma , fit this patient’s age group, as all frequently

Melorheostosis mimicking synovial osteochondromatosis.

PubMed

Wadhwa, Vibhor; Chhabra, Avneesh; Samet, Jonathan D

2014-01-01

Melorheostosis is an uncommon, sporadic, sclerosing bone lesion that may affect the adjacent soft tissues. It has been associated with many entities such as osteopoikilosis, soft tissue vascular malformations, bone and soft tissue tumors, nephrotic syndrome, segmental limb contractures, osteosarcoma, desmoid tumor, and mesenteric fibromatosis. Synovial osteochondromatosis is a benign neoplasia of the hyaline cartilage presenting as nodules in the subsynovial tissue of a joint or tendon sheath. The intra-articular extension of melorheostosis mimicking synovial osteochondromatosis has not been reported before. In this article, the authors describe an unusual case mimicking synovial chondromatosis arising as a result of melorheostosis and their characteristic imaging findings.

Peripheral vestibular pathology in Mondini dysplasia.

PubMed

Kaya, Serdar; Hızlı, Ömer; Kaya, Fatıma Kübra; Monsanto, Rafael DaCosta; Paparella, Michael M; Cureoglu, Sebahattin

2017-01-01

In this study, our objective was to histopathologically analyze the peripheral vestibular system in patients with Mondini dysplasia. Comparative human temporal bone study. We assessed the sensory epithelium of the human vestibular system with a focus on the number of type I and type II hair cells, as well as the total number of hair cells. We compared those numbers in our Mondini dysplasia group versus our control group. The loss of type I and type II hair cells in the cristae of the superior, lateral, and posterior semicircular canals, as well as in the saccular and utricular macula, was significantly higher in our Mondini dysplasia group than in our control group. The total number of hair cells significantly decreased in the cristae of the superior, lateral, and posterior semicircular canals, as well as in the saccular and utricular macula, in our Mondini dysplasia group. Loss of vestibular hair cells can lead to vestibular dysfunction in patients with Mondini dysplasia. NA Laryngoscope, 127:206-209, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Ectodermal dysplasia associated with sickle cell disease.

PubMed

Volpato, Luiz Evaristo Ricci; Volpato, Maria Carmen Palma Faria; de Carvalhosa, Artur Aburad; Palma, Vinicius Canavarros; Borges, Alvaro Henrique

2014-01-01

Ectodermal dysplasia and sickle cell anaemia are inherited disorders that affect, respectively, the tissues derived from the embryonic ectoderm and the production of erythrocytes by the bone marrow. The simultaneous occurrence of both disorders is extremely rare. This is a case of both ectodermal dysplasia and sickle cell anaemia reported in a 6-year-old. The patient had been diagnosed with sickle cell anaemia for only six months when he sought treatment presenting with the following: hypotrichosis, dry skin, periocular hyperpigmentation, protruding lips, hypodontia, and morphologically altered teeth. The clinical features combined with his medical history led to the diagnosis of ectodermal dysplasia. Dentists should be prepared to recognise patterns that escape normality to aid in the diagnosis of systemic changes, even in patients with other previous diagnoses.

'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

PubMed

Gregson, C L; Steel, S A; O'Rourke, K P; Allan, K; Ayuk, J; Bhalla, A; Clunie, G; Crabtree, N; Fogelman, I; Goodby, A; Langman, C M; Linton, S; Marriott, E; McCloskey, E; Moss, K E; Palferman, T; Panthakalam, S; Poole, K E S; Stone, M D; Turton, J; Wallis, D; Warburton, S; Wass, J; Duncan, E L; Brown, M A; Davey-Smith, G; Tobias, J H

2012-02-01

High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

[Prophylactic osteotomy of pelvis in dysplastic acetabulum.].

PubMed

Richtr, M; Sosna, A

1998-01-01

Acetabular dysplasia and anatomical changes of pelvis accompanied with gracility of iliac bone pose a problem for a reliable fixation of acetabular component. In extreme cases the bone stock is not sufficient to accommodate the smallest size of the cup. Sometimes even reaming of the bed down to lamina interna is not sufficient for an adequate covering of the implant. Consequently, weakening of the bottom of acetabulum may be not only one of the causes of the failure of the implant but it makes difficult also the following revision surgeries. Therefore in acetabular dysplasia the authors recommend acetabuloplasty of the bottom of acetabulum preserving its original thickness including inner cortex. They recommend to perform osteotomy of the full thickness of the medial wall of acetabulum and move the massive bone graft created in this way farther into pelvis. At the same time they take care to preserve blood supply of the bone graft by retaining corticoperiostal bridge by means of osteoclasia. The suggested procedure allows full coverage of the implant by iliac bone and at the same time preserves a firm support of acetabular fossa. The original thickness of the medial wall of acetabulum is considered by authors as a significant antimigration barrier. In the period 1991 -1994 the authors used this method at Ist Orthopaedic Clinic of 1st Medical Faculty, Charles University in Prague in total in 16 patients. In all of them after 6 months the bone graft was fully absorbed. Remodelling of the bone graft occurred 1 to 2 years after the surgery and after that the thickness of the graft remained the same. Neither any change of the structure nor reduction of the thickness of the graft was found between 3rd and 4th year after the surgery. The nature of trabecular remodelling of the bone graft corresponds to the transfer of forces in loading the graft by acetabular cup. Key words: acetabuloplasty, osteotomy of the medial wall of acetabulum, osteotomy of pelvis, THR, acetabular dysplasia.

Case report: prenatal diagnosis of diastrophic dysplasia by ultrasound at 21 weeks of gestation in a mother with massive obesity.

PubMed

Jung, C; Sohn, C; Sergi, C

1998-04-01

Routine prenatal ultrasound of a massively obese mother at 21 weeks of gestation revealed short-limb dwarfism in the fetus. The proportionate shortening of tubular bones of about 50 per cent of the normal length, the absence of thoracic dysplasia, and a normal head circumference narrowed the diagnosis down to a severe but non-lethal skeletal dysplasia. Ulnar deviation of the hands and talipes made diastrophic dysplasia the most likely differential diagnosis. At post-mortem clinical examination, the diagnosis of diastrophic dysplasia was clearly apparent due to highly specific 'hitch-hiker thumbs', similarly luxated big toes, facial dysmorphism, and a cleft palate. Retrospective re-evaluation of the prenatal ultrasound videos revealed the misplaced thumbs, which together with the ulnar deviation of the wrist and suspected talipes, led to the conclusion that the definitive diagnosis can be established prenatally, even in a mother with massive obesity.

Cemento-osseous dysplasia in Jamaica: review of six cases.

PubMed

Ogunsalu, C; Miles, D

2005-09-01

Six cases of cemento-osseous dysplasia (COD) of the jaw bone in Jamaicans are reviewed. Five were documented over a 15-year period (1980-1995). These include a case of florid cemento-osseous dysplasia (previously called gigantiform cementoma). Three of the initial cases were histologically diagnosed as gigantiform cementoma. There was no indication in the patient's case file whether these were familial or non-familial. The other two cases were diagnosed histologically as periapical cemento-osseous dysplasia and cementoblastoma respectively. Based on the current understanding of the nature of florid-cemento-osseous dysplasia (FLCOD), a new case was diagnosed as such solely on radiological findings. This single case of FLCOD is reported and discussed against the background of other cemento-osseous lesions. Special emphasis is placed on the radiology of COD in this paper. The confirmative role of radiology without the need for histophathology and treatment for asymptomatic FLCOD is emphasized.

Moore-Federman syndrome and acromicric dysplasia: are they the same entity?

PubMed Central

Winter, R M; Patton, M A; Challener, J; Mueller, R F; Baraitser, M

1989-01-01

Four unrelated patients are reported with short stature, stiffness of the joints, short fingers, inability to make a fist, and thickened skin on the forearms. Investigations have failed to show a lysosomal storage disorder and radiographs show non-specific changes with a delayed carpal bone age. The clinical features in the four children are very similar to the recently described acromicric dysplasia. There are also similarities to Moore-Federman syndrome which has only been described in one family. The case is made that acromicric dysplasia and Moore-Federman syndrome are the same entity. Images PMID:2732993

Mesenchymal stem cells in combination with erythropoietin repair hyperoxia-induced alveoli dysplasia injury in neonatal mice via inhibition of TGF-β1 signaling.

PubMed

Luan, Yun; Zhang, Luan; Chao, Sun; Liu, Xiaoli; Li, Kaili; Wang, Yibiao; Zhang, Zhaohua

2016-07-26

The aim of the present study is to investigate the protection effects of bone marrow mesenchymal stem cells (MSCs) in combination with EPO against hyperoxia-induced bronchopulmonary dysplasia (BPD) injury in neonatal mice. BPD model was prepared by continuous high oxygen exposure, 1×106 bone marrow MSCs and 5000U/kg recombinant human erythropoietin (EPO) were injected respectively. Results showed that administration of MSCs, EPO especially MSCs+EPO significant attenuated hyperoxia-induced lung damage with a decrease of fibrosis, radical alveolar counts and inhibition of the occurrence of epithelial-mesenchymal transition (EMT). Furthermore, MSCs+EPO co-treatment more significantly suppressed the levels of transforming growth factor-β1(TGF-β1) than MSCs or EPO alone. Collectively, these results suggested that MSCs, EPO in particular MSCs+EPO co-treatment could promote lung repair in hyperoxia-induced alveoli dysplasia injury via inhibition of TGF-β1 signaling pathway to further suppress EMT process and may be a promising therapeutic strategy.

Detection of melorheostosis in a young lady with upper limb pain on Three Phase Bone Scintigram/SPECT-CT

PubMed Central

Hassan, Aamna; Khalid, Madeeha; Khawar, Saquib

2016-01-01

Summary Melorheostosis is a benign, noninheritable bone dysplasia characterized by its classic radiographic features of dense, flowing hyperostosis. It frequently affects one limb, usually the lower extremity and rarely the axial skeleton. A 26-year-old lady with obesity, polycystic ovarian syndrome and scalp dandruff presented with a long standing history of upper extremity pain and inability to adduct the arm completely. A Tc-99m MDP whole body and SPECT/CT scan performed for suspected fibrous dysplasia showed increased radiotracer uptake in densely sclerotic humeral and radial melorheostosis. This case highlighted the role of SPECT/CT imaging in this rare condition. PMID:27252746

Osseous dysplasia (cemento-osseous dysplasia) of the jaw bones in western Pennsylvania patients: analysis of 35 cases.

PubMed

Owosho, Adepitan A; Potluri, Anitha; Bilodeau, Elizabeth A

2013-01-01

The purpose of this study is to analyze the demographic, clinical, and radiographic presentations of osseous dysplasia of the jaws in western Pennsylvania patients and its associated complications. The clinical records and radiographs of patients diagnosed with osseous (cement-osseous) dysplasia were retrieved from the electronic health record of the University of Pittsburgh, School of Dental Medicine from 2007 to 2012. All cases were reviewed; the WHO criteria and classification for osseous dysplasia was used. Clinical and demographic data, radiographic findings, and final diagnoses were collected and analyzed. 35 cases of osseous dysplasia were retrieved over the six-year period.The majority (33) were females [94.3%], with ages ranging from 26 to 89 years, with a mean age of 53.9 years +/- standard deviation of 15.6 years, 32 [91.4%] were African Americans and 3 [8.6%] were Caucasians. 17 [48.6%] were florid osseous dysplasia, 13 [37.1%] periapical osseous dysplasia and 5 [14.3%] focal osseous dysplasia. Of the 35 patients only 8 [22.9%] patients were symptomatic. All florid osseous dysplasia patients were African American females, with 7 of the patients being symptomatic and the commonest symptom being pain. Also, all periapical osseous dysplasia patients were African Americans (12 females and 1 male), with 1 of the patients presenting with widening of the diastema. Of the focal osseous dysplasia patients, 3 were Caucasians and 2 African American (4 females and 1 male). The cases occurred mostly in African American females with a peak incidence in the fifth and sixth decades of life; most cases occurred in the mandible. The commonest form of osseous dysplasias was the florid osseous dysplasia which is most likely to present with symptoms.

A mouse model offers novel insights into the myopathy and tendinopathy often associated with pseudoachondroplasia and multiple epiphyseal dysplasia

PubMed Central

Piróg, Katarzyna A.; Jaka, Oihane; Katakura, Yoshihisa; Meadows, Roger S.; Kadler, Karl E.; Boot-Handford, Raymond P.; Briggs, Michael D.

2010-01-01

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are relatively common skeletal dysplasias belonging to the same bone dysplasia family. PSACH is characterized by generalized epi-metaphyseal dysplasia, short-limbed dwarfism, joint laxity and early onset osteoarthritis. MED is a milder disease with radiographic features often restricted to the epiphyses of the long bones. PSACH and some forms of MED result from mutations in cartilage oligomeric matrix protein (COMP), a pentameric glycoprotein found in cartilage, tendon, ligament and muscle. PSACH-MED patients often have a mild myopathy characterized by mildly increased plasma creatine kinase levels, a variation in myofibre size and/or small atrophic fibres. In some instances, patients are referred to neuromuscular clinics prior to the diagnosis of an underlying skeletal dysplasia; however, the myopathy associated with PSACH-MED has not previously been studied. In this study, we present a detailed study of skeletal muscle, tendon and ligament from a mouse model of mild PSACH harbouring a COMP mutation. Mutant mice exhibited a progressive muscle weakness associated with an increased number of muscle fibres with central nuclei at the perimysium and at the myotendinous junction. Furthermore, the distribution of collagen fibril diameters in the mutant tendons and ligaments was altered towards thicker collagen fibrils, and the tendons became more lax in cyclic strain tests. We hypothesize that the myopathy in PSACH-MED originates from an underlying tendon and ligament pathology that is a direct result of structural abnormalities to the collagen fibril architecture. This is the first comprehensive characterization of the musculoskeletal phenotype of PSACH-MED and is directly relevant to the clinical management of these patients. PMID:19808781

[Bone diseases].

PubMed

Uebelhart, Brigitte; Rizzoli, René

2016-01-13

Calcium intake shows a small impact on bone mineral density and fracture risk. Denosumab is a more potent inhibitor of bone resorption than zoledronate. Abaloparatide, PTHrP analog, increases bone mineral density and decreases fracture incidence. Teriparatide could be delivered via a transdermic device. Romosozumab and odanacatib improve calculated bone strength. Sequential or combined treatments with denosumab and teriparatide could be of interest, but not denosumab followed by teriparatide. Fibrous dysplasia, Paget disease and hypophosphatasia are updated, as well as atypical femoral fracture and osteonecrosis of the jaw.

Prenatal ultrasound and MRI findings of temporal and occipital lobe dysplasia in a twin with achondroplasia.

PubMed

Pugash, D; Lehman, A M; Langlois, S

2014-09-01

Thanatophoric dysplasia, hypochondroplasia and achondroplasia are all caused by FGFR3 (fibroblast growth factor receptor 3) mutations. Neuropathological findings of temporal lobe dysplasia are found in thanatophoric dysplasia, and temporal and occipital lobe abnormalities have been described recently in brain imaging studies of children with hypochondroplasia. We describe twins discordant for achondroplasia, in one of whom the prenatal diagnosis was based on ultrasound and fetal MRI documentation of temporal and occipital lobe abnormalities characteristic of hypochondroplasia, in addition to the finding of short long bones. Despite the intracranial findings suggestive of hypochondroplasia, achondroplasia was confirmed following postnatal clinical and genetic testing. These intracranial abnormalities have not been previously described in a fetus with achondroplasia. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Ectodermal Dysplasia Associated with Sickle Cell Disease

PubMed Central

Volpato, Luiz Evaristo Ricci; Volpato, Maria Carmen Palma Faria; de Carvalhosa, Artur Aburad; Palma, Vinicius Canavarros; Borges, Álvaro Henrique

2014-01-01

Ectodermal dysplasia and sickle cell anaemia are inherited disorders that affect, respectively, the tissues derived from the embryonic ectoderm and the production of erythrocytes by the bone marrow. The simultaneous occurrence of both disorders is extremely rare. This is a case of both ectodermal dysplasia and sickle cell anaemia reported in a 6-year-old. The patient had been diagnosed with sickle cell anaemia for only six months when he sought treatment presenting with the following: hypotrichosis, dry skin, periocular hyperpigmentation, protruding lips, hypodontia, and morphologically altered teeth. The clinical features combined with his medical history led to the diagnosis of ectodermal dysplasia. Dentists should be prepared to recognise patterns that escape normality to aid in the diagnosis of systemic changes, even in patients with other previous diagnoses. PMID:25343049

Individualized Plastic Reconstruction Strategy for Patients With Ectodermal Dysplasia Syndrome.

PubMed

Hou, Yikang; Jin, Yunbo; Lin, Xiaoxi; Chai, Gang; Zhang, Yan; Qi, Zuoliang

2017-06-01

Ectodermal dysplasia syndrome is a hereditary disease of ectodermal origin. Appearances of nail dystrophy, alopecia or hypotrichosis, saddle nose deformity, and palmoplantar hyperkeratosis are usually associated with a lack of sweat glands as well as partial or complete absence of teeth. These manifestations are usually corrected only with oral rehabilitation by mounting dentures. In this study, plastic rehabilitation was developed to correct the special features of patients with ectodermal dysplasia. Four men and 1 woman with ectodermal dysplasia syndrome were treated. Four patients showed dysostosis of the midface, and rhinoplasty with costal bone was performed, whereas cosmetic operation aiming to repair soft tissue defects was adopted for the last patient. After plastic corrections, all 5 patients were satisfied with the results and had no social embarrassment.

Is There an Association Between Borderline-to-mild Dysplasia and Hip Osteoarthritis? Analysis of CT Osteoabsorptiometry.

PubMed

Irie, Tohru; Takahashi, Daisuke; Asano, Tsuyoshi; Arai, Ryuta; Terkawi, Muhammad Alaa; Ito, Yoichi M; Iwasaki, Norimasa

2018-07-01

The definitive treatment of borderline-to-mild dysplasia remains controversial. A more comprehensive understanding of the etiology of osteoarthritis (OA) and clarification of any possible association between borderline-to-mild dysplasia and the pathogenesis of OA are essential. (1) Does the distribution of acetabular subchondral bone density increase according to dysplasia severity? (2) Is there an association between borderline-to-mild dysplasia and OA pathogenesis? We evaluated bilateral hips of patients with developmental dysplasia of the hip who underwent eccentric rotational acetabular osteotomy (ERAO) for inclusion in the dysplasia group and contralateral hips of patients with unilateral idiopathic osteonecrosis of the femoral head (ONFH) who underwent curved intertrochanteric varus osteotomy (CVO) for the control group. ERAO was performed in 46 patients and CVO was performed in 32 patients between January 2013 and August 2016 at our institution. All patients underwent bilateral hip CT. The study included 55 hips categorized according to dysplasia severity: (1) borderline-mild, 19 hips (15° ≤ lateral center-edge angle [LCEA] < 25°); (2) moderate, 20 hips (5° ≤ LCEA < 15°); (3) severe, 16 hips (LCEA < 5°); and (4) control, 15 hips. Thirty-seven dysplastic hips (age < 15 or > 50 years old, prior hip surgery, subluxation, aspherical femoral head, cam deformity, and radiographic OA) and 17 control hips (age < 15 or > 50 years old, bilateral ONFH, LCEA < 25° or ≥ 35°, cam deformity, and radiographic OA) were excluded. CT-osteoabsorptiometry (OAM) predicts physiologic biomechanical conditions in joints by evaluating subchondral bone density. We evaluated the distribution of subchondral bone densities in the acetabulum with CT-OAM, dividing the stress distribution map into six segments: anteromedial, anterolateral, centromedial, centrolateral, posteromedial, and posterolateral. We calculated the percentage of high-density area, which was defined as the upper 30% of Hounsfield units values in each region and compared least square means difference estimated by the random intercept model among the four groups. In all regions, the percentage of high-density area did not differ between the borderline-mild group and the control (eg, anterolateral, 16.2 ± 5.6 [95% CI, 13.4 to 18.9] versus 15.5 ± 5.7 [95% CI, 12.4 to 18.5, p = 0.984]; centrolateral, 39.1 ± 5.7 [95% CI, 36.4 to 41.8] versus 39.5 ± 4.7 [95% CI, 36.6 to 42.5, p = 0.995]; posterolateral, 10.9 ± 5.2 [95% CI, 8.0 to 13.8] versus 15.1 ± 6.8 [95% CI, 11.7 to 18.5, p = 0.389]). In the anterolateral region, a smaller percentage of high-density area was observed in the borderline-mild group than in both the moderate group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 28.2 ± 5.1 [95% CI, 25.5-30.9], p < 0.001) and the severe group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 22.2 ± 6.8 [95% CI, 19.2-25.2, p = 0.026). Our results suggest that the cumulative hip stress distribution in borderline-to-mild dysplasia was not concentrated on the lateral side of the acetabulum, unlike severe dysplasia. Based on the stress distribution pattern, our results may suggest that there is no association between borderline-to-mild dysplasia and the pathogenesis of OA. Further studies are needed to evaluate the association between borderline-to-mild dysplasia and instability of the hip.

[Progress in the diagnosis of florid cemento-osseous dysplasia].

PubMed

Zhang, P Y; Xiao, C

2018-04-09

Florid cemento-osseous dysplasia (FLCOD) is a rare, extensive bone metabolism disorder, which occurs only in the jaw bone. It is usually asymptomatic for a long time and discovered incidentally during a radiological examination. The characteristics of FLCOD in the initial stages are similar to those of periapical granuloma or jaw cyst, which may lead to misdiagnosis. After the lesion is mature, the imaging findings show that radiopaque with a thin radiolucent peripheral halo, which is crucial for the diagnosis of FLCOD, but other jaw lesions have similar imaging findings. Due to the poor blood supply of the lesion, the alveolar bone of root apices of vital teeth is slow to heal after trauma, increasing the chance of infection, which can lead to the osteomyelitis of the jaws and emerge sequestrum. This paper reviews the aspects of pathogenesis, clinical characteristics, diagnosis, differential diagnosis and treatment.

Oral Rehabilitation of Adult Edentulous Siblings Severely Lacking Alveolar Bone Due to Ectodermal Dysplasia: A Report of 2 Clinical Cases and a Literature Review.

PubMed

Wu, Yiqun; Zhang, Chenping; Squarize, Cristiane H; Zou, Duohong

2015-09-01

The oral conditions of adult edentulous patients with ectodermal dysplasia (ED) often lead to decreased physical and psychological health, and the negative effects can become as extreme as social and psychological isolation. However, restoring oral function of adult edentulous patients with ED using zygomatic implants (ZIs) or conventional implants (CIs) remains challenging for dentists because of the severe atrophy of these patients' alveolar ridges. This report describes 2 cases of adult edentulous siblings with ED; they exhibited severe alveolar bone atrophy and were treated with ZIs and CIs as bases to augment the bone in their anterior jaws. For these patients, bone augmentation was completed with an autogenous fibular graft. Although there was mild evidence of bone graft resorption in the maxilla, the bone augmentation procedures were successful in the 2 patients. Effective osseointegration of the implants was obtained. After placement, the functional and esthetic results of the oral rehabilitation were acceptable. More importantly, restoration of the patients' oral function enhanced their self-confidence and self-esteem. Therefore, restoring oral function in adult patients with ED and edentulous jaws using ZIs and CIs as the bases for bone augmentation is an effective approach. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

CT of the "Tegernsee Giant": juvenile gigantism and polyostotic fibrous dysplasia.

PubMed

Vogl, T J; Nerlich, A; Dresel, S H; Bergman, C

1994-01-01

We report the radiological findings in the unusual case of the Bavarian "Tegernsee Giant." With conventional radiography, CT, and histologic examination, we succeeded in diagnosing two disorders: The Tegernsee Giant suffered from (a) juvenile gigantism caused by a growth hormone-secreting tumor of the pituitary gland and (b) a polyostotic form of fibrous dysplasia of the skull and multiple bones particularly on the left side of the body.

Evaluation of the Reliability and Validity of the Crawford Classification of Congenital Tibial Dysplasia

DTIC Science & Technology

2007-12-01

Month 1): a. Train a research coordinator to identify potential radiographs at pediatric orthopedic hospital. b. Have conference call with...JR. Delayed autogenous bone graft in the treatment of congenital pseudarthrosis. J Bone Joint Surg Am 1949;31:23. 8. Rudicel S. The orthopaedic

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory

PubMed Central

Jones, Watson; Roberts, R. E.

1933-01-01

(1) Pathology of calcification and ossification.—The Leriche-Policard theories. Hyperæmia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. “Myositis ossificans.” (2) Radiological significance of density of bone shadows.—Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular. (3) Hyperæmic decalcification of bone.—Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperæmic dislocation of the atlas. Hyperæmic decalcification and nephrolithiasis. (4) Anæmic sclerosis of bone.—Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone—Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases. (5) Pathological calcification.—Calcification of supraspinatus tendon. Calcification of tumours—angioma, hæmatoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs. (6) Pathological ossification.—Ossification of tendons. Ossification of semilunar cartilages. PMID:19989304

Spondyloenchondrodysplasia: a rare cause of short stature.

PubMed

Yeşiltepe-Mutlu, Gül; Ozsu, Elif; Cizmecioğlu, Filiz Mine; Alanay, Yasemin; Hatun, Sükrü

2011-01-01

Skeletal dysplasias (osteochondrodysplasias) are a group of diseases that must be included in the differential diagnosis of disproportionate short stature. History, clinical and radiologic findings and consanguinity are important features to be considered when a specific diagnosis is investigated. Spondyloenchondrodysplasia is a very rare skeletal dysplasia characterized with enchondromas in the long bones and platyspondyly. Manifestation of the disorder may include neurological involvement (spasticity, intracranial calcifications and mental retardation) and immune dysfunction. Herein, we report a 12-year-old boy who admitted to our clinic with short stature, who was born to consanguineous parents. He presented clinical (significant widening of wrists, ankles and knees) and radiologic (enchondromatous lesions in the metaphysis of long bones) features of spondyloenchondrodysplasia but did not yet have neurologic or immunologic involvement.

[Traumatic spondylolysis in the hedgehog. A contribution to the problem of isthmus dysplasia].

PubMed

Roth, M

1994-01-01

Traumatic spondylolysis in a hedgehog is reported. On the basis of that rare observation the "dysplastic" thinning of the vertebral isthmus frequently associated with spondylolysis in man is claimed to be related to the "neuroenveloping" function of the spine shared with that of the neurocranium. Dysplasia of the isthmus results from abnormal ganglio-foraminal interrelation in the embryo rather than from any primary derangement of the vertebral bone growth proper.

A Conditional Knockout Mouse Model Reveals a Critical Role of PKD1 in Osteoblast Differentiation and Bone Development

PubMed Central

Li, Shao; Xu, Wanfu; Xing, Zhe; Qian, Jiabi; Chen, Liping; Gu, Ruonan; Guo, Wenjing; Lai, Xiaoju; Zhao, Wanlu; Li, Songyu; Wang, Yaodong; Wang, Q. Jane; Deng, Fan

2017-01-01

The protein kinase D family of serine/threonine kinases, particularly PKD1, has been implicated in the regulation of a complex array of fundamental biological processes. However, its function and mechanism underlying PKD1-mediated the bone development and osteoblast differentiation are not fully understood. Here we demonstrate that loss of PKD1 function led to impaired bone development and osteoblast differentiation through STAT3 and p38 MAPK signaling using in vitro and in vivo bone-specific conditional PKD1-knockout (PKD1-KO) mice models. These mice developed markedly craniofacial dysplasia, scapula dysplasia, long bone length shortage and body weight decrease compared with wild-type littermates. Moreover, deletion of PKD1 in vivo reduced trabecular development and activity of osteoblast development, confirmed by Micro-CT and histological staining as well as expression of osteoblastic marker (OPN, Runx2 and OSX). Mechanistically, loss of PKD1 mediated the downregulation of osteoblast markers and impaired osteoblast differentiation through STAT3 and p38 MAPK signaling pathways. Taken together, these results demonstrated that PKD1 contributes to the osteoblast differentiation and bone development via elevation of osteoblast markers through activation of STAT3 and p38 MAPK signaling pathways. PMID:28084409

Mandibular Actinomyces osteomyelitis complicating florid cemento-osseous dysplasia: case report

PubMed Central

2011-01-01

Background Apart from neoplastic processes, chronic disfiguring and destructive diseases of the mandible are uncommon. Case Presentation We report, perhaps for the first time, the simultaneous occurrence of two such conditions in one patient, in a case that emphasizes the importance of bone biopsy in establishing the correct diagnosis. Florid cemento-osseous dysplasia (FCOD) is a chronic, disfiguring condition of the maxillofacial region. This relatively benign disease is primarily observed in middle-aged women of African ancestry. Cervicofacial actinomycosis is an uncommon and progressive infection caused by bacilli of the Actinomyces genus that typically involves intraoral soft tissues but may also involve bone. The accurate diagnosis of actinomycosis is critical for successful treatment. A diagnosis of osteomyelitis caused by Actinomyces bacteria was diagnosed by bone biopsy in a 53 year-old African-American woman with a longstanding history of FCOD after she presented with a new draining ulcer overlying the mandible. Conclusions Clinicians should be aware of the possibility of actinomycosis arising in the setting of FCOD, and the importance of bone biopsy and cultures in arriving at a definitive and timely diagnosis. PMID:21777471

Mandibular Actinomyces osteomyelitis complicating florid cemento-osseous dysplasia: case report.

PubMed

Smith, Miller H; Harms, Paul W; Newton, Duane W; Lebar, Bill; Edwards, Sean P; Aronoff, David M

2011-07-21

Apart from neoplastic processes, chronic disfiguring and destructive diseases of the mandible are uncommon. We report, perhaps for the first time, the simultaneous occurrence of two such conditions in one patient, in a case that emphasizes the importance of bone biopsy in establishing the correct diagnosis. Florid cemento-osseous dysplasia (FCOD) is a chronic, disfiguring condition of the maxillofacial region. This relatively benign disease is primarily observed in middle-aged women of African ancestry. Cervicofacial actinomycosis is an uncommon and progressive infection caused by bacilli of the Actinomyces genus that typically involves intraoral soft tissues but may also involve bone. The accurate diagnosis of actinomycosis is critical for successful treatment. A diagnosis of osteomyelitis caused by Actinomyces bacteria was diagnosed by bone biopsy in a 53 year-old African-American woman with a longstanding history of FCOD after she presented with a new draining ulcer overlying the mandible. Clinicians should be aware of the possibility of actinomycosis arising in the setting of FCOD, and the importance of bone biopsy and cultures in arriving at a definitive and timely diagnosis.

Familial subacute sclerosing panencephalitis associated with short latency.

PubMed

Sharma, Vinod; Gupta, Vineet B; Eisenhut, Michael

2008-03-01

The familial recurrence of subacute sclerosing panencephalitis is rare. The study of such cases and a comparison of intrafamilial with sporadic cases of subacute sclerosing panencephalitis may shed light on important pathogenetic factors. We report on the occurrence of subacute sclerosing panencephalitis in two brothers from rural India, who contracted measles infection simultaneously at ages 3 and 11 years. They developed subacute sclerosing panencephalitis 21 and 37 months later, respectively. A diagnosis of subacute sclerosing panencephalitis was based on history, electroencephalographic changes, and significantly raised levels of cerebrospinal-fluid anti-measles virus immunoglobulin G. A comparison of intrafamilial with sporadic cases of subacute sclerosing panencephalitis revealed that latency in familial subacute sclerosing panencephalitis involved a median of 6.4 years (range, 1.0-10.9), significantly (P < 0.05) shorter than in sporadic cases with a median of 9.7 years (range, 2.7-23.4). This difference was because of significantly later infection with measles virus and an earlier onset of encephalitis. We describe the first siblings affected by subacute sclerosing panencephalitis from the Indian subcontinent. We confirmed a more rapid manifestation of subacute sclerosing panencephalitis after measles virus infection in intrafamilial compared with sporadic subacute sclerosing panencephalitis.

Gigantism treated by pure endoscopic endonasal approach in a case of McCune-Albright syndrome with sphenoid fibrous dysplasia: a case report.

PubMed

Sharifi, Guive; Jalessi, Maryam; Sarvghadi, Farzaneh; Farhadi, Mohammad

2013-12-01

McCune-Albright syndrome (MAS) is an uncommon polyostotic manifestation of fibrous dysplasia in association with at least one endocrinopathy that is mostly associated with precocious puberty and hyperpigmented skin macules named café-au-lait spots. We present an atypical manifestation of McCune-Albright syndrome in a 19-year-old man with the uncommon association of polyostotic fibrous dysplasia and gigantism in the absence of café-au-lait spots and precocious puberty. He presented with a height increase to 202 cm in the previous 3 years, which had become more progressive in the few months prior. Physical examination revealed only a mild facial asymmetry; however, a computed tomography (CT) scan discovered vast areas of voluminous bones with ground-glass density and thickening involving the craniofacial bones and skull base. Magnetic resonance imaging (MRI) found a right stalk shift of the pituitary with a 20 mm pituitary adenoma. We describe the diagnostic and endoscopic endonasal transsphenoidal approach for excision of the tumor. Georg Thieme Verlag KG Stuttgart · New York.

A Neolithic case of fibrous dysplasia from Çatalhöyük (Turkey).

PubMed

Milella, Marco; Knüsel, Christopher J; Haddow, Scott D

2016-12-01

The vast majority of primary burials at Neolithic Çatalhöyük (Central Anatolia, Turkey, 7100-6000cal BC) are recovered from beneath house floors, with burials in external spaces extremely rare. Excavations at Çatalhöyük in 1998 brought to light a young adult male buried in a midden (a burial location observed so far for only 4 out of 440 individuals), showing a suite of pathological features affecting the entire skeleton. The observed pathological changes include perimortem and antemortem fractures, proliferative and resorptive areas, thinning of the bone cortex, and localized areas of disorganized spongy bone invaded by fibrous tissue. We propose a differential diagnosis by considering a set of conditions: Paget's disease, osteomyelitis, hyperparathyrhoidism, Ollier's disease, fibrosarcoma, and fibrous dysplasia. The severity and distribution of the observed skeletal changes are consistent with a diagnosis of polyostotic fibrous dysplasia, a possibly debilitating and disfiguring condition. This, together with an unusual depositional context, may suggest a socially-mediated reaction to this individual's infirmity. Copyright © 2016 Elsevier Inc. All rights reserved.

Sphenoid dysplasia in neurofibromatosis type 1: a new technique for repair.

PubMed

Concezio, Di Rocco; Amir, Samii; Gianpiero, Tamburrini; Luca, Massimi; Mario, Giordano

2017-06-01

Sphenoid bone dysplasia in neurofibromatosis type 1 is characterized by progressive exophthalmos and facial disfiguration secondary to herniation of meningeal and cerebral structures. We describe a technique for reconstruction of the sphenoid defect apt at preventing or correcting the ocular globe dislocation. After placement of spinal cerebrospinal fluid drainage to reduce intracranial pressure, the temporal pole is posteriorly dislocated extradurally. The greater sphenoid wing defect is identified. A titanium mesh covered by lyophilized dura, modeled in a curved fashion, is interposed between the bone defect and the cerebro-meningeal structures with its convex surface over the retracted temporal pole. The particular configuration of the titanium mesh allows a self-maintaining position due to the pressure exerted by the brain over its convex central part with its lateral margins consequently pushed and self-anchored against the medial and lateral walls of the temporal fossa. Screw fixation is not needed. The technique utilized in four cases proved to be reliable at the long-term clinical and neuroradiological controls (6 to 19 years). Sphenoid bone dysplasia in NF1, resulting in proptosis and exophthalmos, is usually progressive. It can be surgically repaired using a curved titanium mesh with the convexity faced to the temporal pole that is in the opposite fashion from all the techniques previously introduced. When utilized early in life, the technique can prevent the occurrence of the orbital and facial disfiguration.

Dental management of florid cemento-osseous dysplosia.

PubMed

Sadda, Raid S; Phelan, Joan

2014-04-01

Cemento-osseous dysplasia encompasses several different clinical and radiographic presentations, including periapical, focal and florid cemento-osseous dysplasia (FCOD). FCOD is usually asymptomatic and discovered only fortuitously. No treatment is required unless the lesion is secondarily infected. Oral hygiene advice should be emphasized for patients with FCOD to prevent caries and periodontal diseases and to maintain natural teeth. Osseointegration of implants would likely not be successful in these patients because the bone is abnormal and not well-vascularized.

A chondrodysplasia family produced by mutations in the diastrophic dysplasia sulfate transporter gene: Genotype/phenotype correlations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Superti-Furga, A.; Steinmann, B.; Gitzelmann, R.

1996-05-03

Achondrogenesis type 1B (ACG-1B), atelosteogenesis type 2 (AO-2), and diastrophic dysplasia (DTD) are recessively inherited chondrodysplasia of decreasing severity caused by mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene on chromosome 5. In these conditions, sulfate transport across the cell membrane is impaired which results in insufficient sulfation of cartilage proteoglycans and thus in an abnormally low sulfate content of cartilage. The severity of the phenotype correlates well with the predicted effect of the underlying DTDST mutations: homozygosity or compound heterozygosity for stop codons or transmembrane domain substitutions mostly result in achondrogenesis type 1B, while other structural or regulatorymore » mutations usually result in one of the less severe phenotypes. The chondrodysplasia arising at the DTDST locus constitute a bone dysplasia family with recessive inheritance. 28 refs., 2 tabs.« less

Sclerosing Cholangitis: Clinicopathologic Features, Imaging Spectrum, and Systemic Approach to Differential Diagnosis.

PubMed

Seo, Nieun; Kim, So Yeon; Lee, Seung Soo; Byun, Jae Ho; Kim, Jin Hee; Kim, Hyoung Jung; Lee, Moon-Gyu

2016-01-01

Sclerosing cholangitis is a spectrum of chronic progressive cholestatic liver disease characterized by inflammation, fibrosis, and stricture of the bile ducts, which can be classified as primary and secondary sclerosing cholangitis. Primary sclerosing cholangitis is a chronic progressive liver disease of unknown cause. On the other hand, secondary sclerosing cholangitis has identifiable causes that include immunoglobulin G4-related sclerosing disease, recurrent pyogenic cholangitis, ischemic cholangitis, acquired immunodeficiency syndrome-related cholangitis, and eosinophilic cholangitis. In this review, we suggest a systemic approach to the differential diagnosis of sclerosing cholangitis based on the clinical and laboratory findings, as well as the typical imaging features on computed tomography and magnetic resonance (MR) imaging with MR cholangiography. Familiarity with various etiologies of sclerosing cholangitis and awareness of their typical clinical and imaging findings are essential for an accurate diagnosis and appropriate management.

[Kniest's syndrome (author's transl)].

PubMed

Kniest, W; Leiber, B

1977-12-01

The clinical picture of the Kniest's syndrome is described. The syndrome is a rare hereditary condition with generalized bone dysplasia, disproportional dwarfism, conduction deafness and severe myopia, retinal detachment, cataract and amaurosis.

Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

ClinicalTrials.gov

2018-05-14

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; CD45-Positive Neoplastic Cells Present; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

[Clinical condition and therapy of bone diseases].

PubMed

Miura, Kohji; Oznono, Keiichi

2013-12-01

Skeletal dysplasia is the term which represents disorders including growth and differentiation of bone, cartilage and ligament. A lot of diseases are included, and new disorders have been added. However, the therapy of most bone diseases is less well-established. Achondroplasia, hypochondroplasia, and osteogenesis imperfecta are most frequent bone diseases. There is no curative treatment for these diseases, however, supportive therapies are available ; for example, growth-hormone therapy for achondroplasia and hypochondroplasia, and bisphosphonate therapy for osteogenesis imperfecta. In addition, enzyme replacement therapy for hypophosphatasia is now on clinical trial.

Determinants of impaired quality of life in patients with fibrous dysplasia.

PubMed

Majoor, Bas C J; Andela, Cornelie D; Bruggemann, Jens; van de Sande, Michiel A J; Kaptein, Ad A; Hamdy, Neveen A T; Dijkstra, P D Sander; Appelman-Dijkstra, Natasha M

2017-04-27

Fibrous dysplasia is a rare bone disorder, commonly associated with pain, deformity and fractures, which may significantly impact on quality of life. In this study we evaluate quality of life in patients with fibrous dysplasia using the Short Form-36 and the Brief Pain Inventory questionnaires. Data were compared with those of the general Dutch population. Out of 138 patients from a cohort of 255 patients with fibrous dysplasia that were sent questionnaires assessing quality of life and pain, the response rate was 70.3%, with 97 patients, predominantly female (65%), completing the questionnaires. Monostotic fibrous dysplasia was predominant (n = 62, 64%). Fibrous dysplasia patients had significantly lower quality of life outcome scores than the general Dutch population for all tested domains of the Short Form-36 except for the "Mental health" and the "Role emotional" domains. More severe forms of fibrous dysplasia, had the more severe Short-Form-36 quality of life outcomes, but there was no significant difference in Brief Pain Inventory domains between different subtypes of fibrous dysplasia. Quality of life was lower in patients with higher disease burden, as reflected by high skeletal burden scores (p = 0.003) and high levels of P1NP (p = 0.002). We demonstrate impairments in all domains of quality of life, except for 'Mental health' and 'Role emotional' domains, across the wide spectrum of fibrous dysplasia including its milder forms. We identified high skeletal burden scores, reflecting disease severity, as the most consistent predictor of impaired quality of life. Our findings hold significant clinical implications as they draw attention to the clinically unmet need to address quality of life issues in the management of patients with all subtypes of fibrous dysplasia, including its milder forms.

Genetics Home Reference: acromicric dysplasia

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Skeletal dysplasia with craniofacial deformity and disproportionate dwarfism in hair sheep of northeastern Brazil.

PubMed

Dantas, F P M; Medeiros, G X; Figueiredo, A P M; Thompson, K; Riet-Correa, F

2014-01-01

This paper reports a newly described form of skeletal dysplasia affecting Brazilian hair sheep of the Cabugi breed. This breed is characterized by having a short head and in some cases the animals are smaller and more compact than sheep of similar breeds. Lambs born with craniofacial abnormalities and dwarfism that die at 2-6 months of age are frequent in this breed. In a flock of 68 ewes and three rams of the Cabugi breed, 134 lambs were born over a 4-year period. Of these, 14 (10.4%) had marked cranial abnormalities and dwarfism and died or were humanely destroyed, 43 (32%) had a normal face and 77 (57.5%) had the short face characteristic of the breed. Dwarf lambs were much smaller than normal, with short legs, a domed head with retruded muzzle and protruded mandible, sternal deformities and exophthalmic eyes situated more laterally in the face than normal. Microscopical examination of long bones of the limbs, bones of the base of the skull and vertebrae showed no lesions. Bones from four affected lambs and one control lamb were macerated for morphometric examination. Although the length of the spinal cord was similar, there was disproportionate shortening of the appendicular bones, particularly the distal segments. Thus the disease was defined as a skeletal dysplasia characterized by craniofacial deformity and disproportionate dwarfism. It is suggested that the disease is inherited as an incomplete dominant trait. The shortened face, which is a feature of the Cabugi breed, may represent the heterozygous state and the more severe, often lethal, dwarfism may occur in homozygotes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bone marrow failure in childhood: central pathology review of a nationwide registry.

PubMed

Ito, Masafumi

2017-01-01

Refractory cytopenia of childhood (RCC) was proposed as a provisional entity in the 2008 WHO classification of myelodysplastic syndromes (MDS). It is defined as a childhood MDS featuring persistent cytopenia without increase blasts in bone marrow (BM) or peripheral blood (PB). Because the majority of RCC cases feature hypocellularity and pancytopenia, it is quite challenging to differentiate RCC from acquired aplastic anemia (AA) and many kinds of inherited bone marrow failure syndromes (IBMFS). Diagnosis of RCC requires BM histology of characteristic features such as isolated erythroid islet with left shift, abnormal localization and micromegakaryocytes. The Japanese Society of Pediatric Hematology/Oncology has opened the central registry review system since 2009 to evaluate childhood cases of bone marrow failure (BMF). It has reviewed cytology and BM pathology of all registered BMF cases, which number more than 1,700. In the evaluation of BMF, BM pathology is important to assess the mechanism of hematopoiesis. Pathological dysplasia should be differentiated from cytological dysplasia. A central review system is important for rare diseases, such as pediatric BMF. Standardization of pathological diagnosis should be established upon consensus findings, descriptions, and diagnostic approaches. In this review, the pathology of pediatric BMF syndromes is summarized.

Non-synonymous FGD3 Variant as Positional Candidate for Disproportional Tall Stature Accounting for a Carcass Weight QTL (CW-3) and Skeletal Dysplasia in Japanese Black Cattle

PubMed Central

Takasuga, Akiko; Sato, Kunio; Nakamura, Ryouichi; Saito, Yosuke; Sasaki, Shinji; Tsuji, Takehito; Suzuki, Akio; Kobayashi, Hiroshi; Matsuhashi, Tamako; Setoguchi, Koji; Okabe, Hiroshi; Ootsubo, Toshitake; Tabuchi, Ichiro; Fujita, Tatsuo; Watanabe, Naoto; Hirano, Takashi; Nishimura, Shota; Watanabe, Toshio; Hayakawa, Makio; Sugimoto, Yoshikazu; Kojima, Takatoshi

2015-01-01

Recessive skeletal dysplasia, characterized by joint- and/or hip bone-enlargement, was mapped within the critical region for a major quantitative trait locus (QTL) influencing carcass weight; previously named CW-3 in Japanese Black cattle. The risk allele was on the same chromosome as the Q allele that increases carcass weight. Phenotypic characterization revealed that the risk allele causes disproportional tall stature and bone size that increases carcass weight in heterozygous individuals but causes disproportionately narrow chest width in homozygotes. A non-synonymous variant of FGD3 was identified as a positional candidate quantitative trait nucleotide (QTN) and the corresponding mutant protein showed reduced activity as a guanine nucleotide exchange factor for Cdc42. FGD3 is expressed in the growth plate cartilage of femurs from bovine and mouse. Thus, loss of FDG3 activity may lead to subsequent loss of Cdc42 function. This would be consistent with the columnar disorganization of proliferating chondrocytes in chondrocyte-specific inactivated Cdc42 mutant mice. This is the first report showing association of FGD3 with skeletal dysplasia. PMID:26306008

Delayed osteon formation in long-bone diaphysis of an 11-year-old giant cow with dermal dysplasia.

PubMed

Mori, R; Kodaka, T; Naito, Y

1999-02-01

The transverse sections of radius diaphysis in an 11-year-old giant Holstein cow with dermal dysplasia of a collagen disorder-related skin fragility (Cow 1), probably based on increasing turnover of the dermal collagen as reported previously, were morphologically and physico-chemically investigated. Cow 1 had about one and a half times as much as the body weight of normal Holstein cows, aged 5 to 6.5 years with stabilized growth. The bone samples were compared with those of a 12-year-old Holstein cow as controls (Cow 2). It has been reported that the long-bone diaphysis of young calves and some herbivorous dinosaurs are occupied with laminar bone showing a concentric appositional formation, and that such a laminar bone is characteristically seen during the growing period of some farm animals and large dogs that show very rapid growth rates. Cow 1 had a smaller number of osteons than Cow 2 in the outer-half layer of the diaphysis, and showed an intermediate type between Cow 2 and a 1-year-old Holstein ox in the entire layers, although their bone volumes were similar among them. There were no significant differences in Ca and P concentrations and the Vickers microhardness values between the bone matrix of Cow 1 and Cow 2. The bone-collagen fibrils of Cow 1 showed uneven diameters and a disordered arrangement. Thus, there may be some relation in collagen formation between the bone matrix of Cow 1 and the dermis. From the remaining volume of laminar bone, Cow 1, aged 11 years, had probably shown growth until quite recently, so that we consider that Cow 1 became a giant animal, in the same way as some herbivorous dinosaurs.

Craniometaphyseal dysplasia with obvious biochemical abnormality and rickets-like features.

PubMed

Wu, Bo; Jiang, Yan; Wang, Ou; Li, Mei; Xing, Xiao-Ping; Xia, Wei-Bo

2016-05-01

Craniometaphyseal dysplasia (CMD) is a rare genetic disorder that is characterized by progressive sclerosis of the craniofacial bones and metaphyseal widening of long bones, and biochemical indexes were mostly normal. To further the understanding of the disease from a biochemical perspective, we reported a CMD case with obviously abnormal biochemical indexes. A 1-year-old boy was referred to our clinic. Biochemical test showed obviously increased alkaline phosphatase (ALP) and parathyroid hormone (PTH), mild hypocalcemia and hypophosphatemia. Moreover, significant elevated receptor activator of nuclear factor kappa-B ligand (RANKL) level, but normal β-C-terminal telopeptide of type I collagen (β-CTX) concentration were revealed. He was initially suspected of rickets, because the radiological examination also showed broadened epiphysis in his long bones. Supplementation with calcium and calcitriol alleviated biochemical abnormality. However, the patient gradually developed osteosclerosis which was inconformity with rickets. Considering that he was also presented with facial paralysis and nasal obstruction symptom, the diagnosis of craniometaphyseal dysplasia was suspected, and then was confirmed by the mutation analysis of ANKH of the proband and his family, which showed a de novo heterozygous mutation (C1124-1126delCCT) on exon 9. Our study revealed that obvious biochemical abnormality and rickets-like features might present as uncommon characteristics in CMD patients, and the calcium and calcitriol supplementation could alleviate biochemical abnormalities. Furthermore, although early osteoclast differentiation factor was excited in CMD patient, activity of osteoclast was still inert. Copyright © 2016. Published by Elsevier B.V.

Genetics Home Reference: Czech dysplasia

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... for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that ... in the nose and external ears. Type II collagen is essential for the normal development of bones ...

Genetics Home Reference: Kniest dysplasia

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... for making a protein that forms type II collagen. This type of collagen is found mostly in the clear gel that ... in the nose and external ears. Type II collagen is essential for the normal development of bones ...

Acrogigantism and facial asymmetry: McCune-Albright syndrome.

PubMed

Subbiah, Sridhar; Palikhe, Gaurav; Bhadada, Sanjay Kumar; Mukherjee, Kanchan Kumar; Bhansali, Anil

2011-01-01

McCune-Albright syndrome (MAS) is characterized by a triad of poly/monoostotic fibrous dysplasia, café-au-lait macules and hyperfunctioning endocrinopathies. Association of MAS with GH excess is rare, and in most of the instances somatotropinoma has not been documented. Treatment of patients of MAS with acromegaly is difficult because of thickened calvarium and dysplastic skull bone. We report a 17-year-old girl, who presented with cranio-facial fibrous dysplasia, café-au-lait macules and also had acromegaly due to pituitary macroadenoma, and treated with gamma knife radiosurgery.

Mutations in FLNB cause boomerang dysplasia

PubMed Central

Bicknell, L; Morgan, T; Bonafe, L; Wessels, M; Bialer, M; Willems, P; Cohn, D; Krakow, D; Robertson, S

2005-01-01

Boomerang dysplasia (BD) is a perinatal lethal osteochondrodysplasia, characterised by absence or underossification of the limb bones and vertebrae. The BD phenotype is similar to a group of disorders including atelosteogenesis I, atelosteogenesis III, and dominantly inherited Larsen syndrome that we have recently shown to be associated with mutations in FLNB, the gene encoding the actin binding cytoskeletal protein, filamin B. We report the identification of mutations in FLNB in two unrelated individuals with boomerang dysplasia. The resultant substitutions, L171R and S235P, lie within the calponin homology 2 region of the actin binding domain of filamin B and occur at sites that are evolutionarily well conserved. These findings expand the phenotypic spectrum resulting from mutations in FLNB and underline the central role this protein plays during skeletogenesis in humans. PMID:15994868

Mutations in FLNB cause boomerang dysplasia.

PubMed

Bicknell, L S; Morgan, T; Bonafé, L; Wessels, M W; Bialer, M G; Willems, P J; Cohn, D H; Krakow, D; Robertson, S P

2005-07-01

Boomerang dysplasia (BD) is a perinatal lethal osteochondrodysplasia, characterised by absence or underossification of the limb bones and vertebrae. The BD phenotype is similar to a group of disorders including atelosteogenesis I, atelosteogenesis III, and dominantly inherited Larsen syndrome that we have recently shown to be associated with mutations in FLNB, the gene encoding the actin binding cytoskeletal protein, filamin B. We report the identification of mutations in FLNB in two unrelated individuals with boomerang dysplasia. The resultant substitutions, L171R and S235P, lie within the calponin homology 2 region of the actin binding domain of filamin B and occur at sites that are evolutionarily well conserved. These findings expand the phenotypic spectrum resulting from mutations in FLNB and underline the central role this protein plays during skeletogenesis in humans.

Periapical cemento-osseous dysplasia: clinicopathological features.

PubMed

Roghi, Marco; Scapparone, Chiara; Crippa, Rolando; Silvestrini-Biavati, Armando; Angiero, Francesca

2014-05-01

Periapical cemento-osseous dysplasia (PCOD) is a rare benign lesion, often asymptomatic, in which fibrous tissue replaces the normal bone tissue, with metaplasic bone and neo-formed cement. We present a rare case of mandibular PCOD in a woman of 55 years, who presented with moderate swelling and mobility of teeth 32-33-34. Endoral radiography showed that these teeth had been devitalized; they had deep periodontal pockets and marked radicular radiotransparency; the root apices exhibited mixed radiotransparency and radio-opacity. Clinical and radiographical findings led to a diagnosis of periapical rarefying osteitis, and the three teeth were thus extracted. Due to the persistence of swelling and slight pain post-extraction, a cone-beam computed tomographic scan was taken; this showed a mixed radiotransparent and radio-opaque lesion in the area of the extracted teeth. A bone biopsy of the affected area was taken for histopathological evaluation; a diagnosis of PCOD was rendered. This case demonstrates the importance of a full investigation when a patient presents after tooth extraction with non-healing socket, pain, and swelling. A multidisciplinary approach is required to manage these rare cases.

Mutations Preventing Regulated Exon Skipping in MET Cause Osteofibrous Dysplasia

PubMed Central

Gray, Mary J.; Kannu, Peter; Sharma, Swarkar; Neyt, Christine; Zhang, Dongping; Paria, Nandina; Daniel, Philip B.; Whetstone, Heather; Sprenger, Hans-Georg; Hammerschmidt, Philipp; Weng, Angela; Dupuis, Lucie; Jobling, Rebekah; Mendoza-Londono, Roberto; Dray, Michael; Su, Peiqiang; Wilson, Megan J.; Kapur, Raj P.; McCarthy, Edward F.; Alman, Benjamin A.; Howard, Andrew; Somers, Gino R.; Marshall, Christian R.; Manners, Simon; Flanagan, Adrienne M.; Rathjen, Karl E.; Karol, Lori A.; Crawford, Haemish; Markie, David M.; Rios, Jonathan J.; Wise, Carol A.; Robertson, Stephen P.

2015-01-01

The periosteum contributes to bone repair and maintenance of cortical bone mass. In contrast to the understanding of bone development within the epiphyseal growth plate, factors that regulate periosteal osteogenesis have not been studied as intensively. Osteofibrous dysplasia (OFD) is a congenital disorder of osteogenesis and is typically sporadic and characterized by radiolucent lesions affecting the cortical bone immediately under the periosteum of the tibia and fibula. We identified germline mutations in MET, encoding a receptor tyrosine kinase, that segregate with an autosomal-dominant form of OFD in three families and a mutation in a fourth affected subject from a simplex family and with bilateral disease. Mutations identified in all families with dominant inheritance and in the one simplex subject with bilateral disease abolished the splice inclusion of exon 14 in MET transcripts, which resulted in a MET receptor (METΔ14) lacking a cytoplasmic juxtamembrane domain. Splice exclusion of this domain occurs during normal embryonic development, and forced induction of this exon-exclusion event retarded osteoblastic differentiation in vitro and inhibited bone-matrix mineralization. In an additional subject with unilateral OFD, we identified a somatic MET mutation, also affecting exon 14, that substituted a tyrosine residue critical for MET receptor turnover and, as in the case of the METΔ14 mutations, had a stabilizing effect on the mature protein. Taken together, these data show that aberrant MET regulation via the juxtamembrane domain subverts core MET receptor functions that regulate osteogenesis within cortical diaphyseal bone. PMID:26637977

Tooth eruption in a patient with craniometaphyseal dysplasia: case report.

PubMed

Hayashibara, T; Komura, T; Sobue, S; Ooshima, T

2000-10-01

Craniometaphyseal dysplasia (CMD) is a very rare genetic disorder of bone remodeling caused by osteoclast dysfunction. The clinical and radiographical features of oral findings are presented in a sporadic case of CMD in a child (age 10 years, 7 months). An intraoral examination showed severe malocclusions, including anterior crossbite and deep bite. Furthermore, a radiographic examination showed increased radiopacity of the maxilla and mandibular bones due to hyperostosis and sclerosis of the jaw. There was no root resorption of the canines or molars in the primary dentition, although root formation of the permanent teeth was proceeding. Dental age was calculated to be approximately 1 year, 4 months younger than his chronological age. The eruption speed of the permanent lateral incisors after the gingival emergence was shown to be within normal values, and we discuss whether the canines and premolars in the permanent dentition could erupt or not.

Single Stage Treatment of Non - Union of Transcervical Neck Femur Fracture with Shepherd Crook Deformity of Proximal Femur in A Case of Fibrous Dysplasia using Dynamic Hip Screw Fixation.

PubMed

Vk, Kandhari; Ss, Bava; Mm, Desai; Rn, Wade

2015-01-01

Fibrous dysplasia is a rare benign disorder of the skeletal system characterized by fibro osseous proliferation with intervening areas of normal or immature bone in the intramedullary region. It can either be a monostotic (involves one bone) or a polyostotic (involves more than one bone) presentation and usually occurs equally in males and females. Deformities like scoliosis and shepherd's crook deformity are frequently encountered in the polyostotic form. We report a rare managed case of bilateral non-union of the pathological fracture of femur neck with shepherd's crook deformity of the proximal femur in a case of polyostotic fibrous dysplasia. A 16 years old female case of polyostotic fibrous dysplasia had bilateral Shepherd's crook deformity of the proximal femur with bilateral non - union of pathological fracture of neck femur. We managed each side in one stage with two osteotomies. On the right side, first oblique osteotomy was done from just distal to the greater trochanter up to the level of the neck and the second; lateral closing wedge abduction osteotomy was done at the subtrochanteric level. 2 months later on the left side double lateral closing wedge abduction osteotomies were performed both at the subtrochanteric level. Fixation of both the sides was done using a 135° Dynamic Richard's screw with a long side plate to span the osteotomy sites and the lesion. Post - operatively we achieved a neck shaft angle of 135° on right side and 133° on the left side. Follow up imaging showed union at both the osteotomy sites bilaterally and also at the site of the pathological fracture of neck femur. Presently, at 18 months post - operatively, patient is walking full weight bearing without support and there are no signs of recurrence of lesions of fibrous dysplasia or the deformity. Double osteotomy is an easy and effective method to correct the shepherd's crook deformity and achieve correct mechanical alignment. Dynamic hip screw with long side plate is a versatile implant to tackle the proximal femur deformity. Double osteotomy corrects the deformity and tackles the associated problems like non - union of the pathological neck femur fracture in one stage.

Single Stage Treatment of Non – Union of Transcervical Neck Femur Fracture with Shepherd Crook Deformity of Proximal Femur in A Case of Fibrous Dysplasia using Dynamic Hip Screw Fixation

PubMed Central

VK, Kandhari; SS, Bava; MM, Desai; RN, Wade

2015-01-01

Introduction: Fibrous dysplasia is a rare benign disorder of the skeletal system characterized by fibro osseous proliferation with intervening areas of normal or immature bone in the intramedullary region. It can either be a monostotic (involves one bone) or a polyostotic (involves more than one bone) presentation and usually occurs equally in males and females. Deformities like scoliosis and shepherd’s crook deformity are frequently encountered in the polyostotic form. We report a rare managed case of bilateral non-union of the pathological fracture of femur neck with shepherd’s crook deformity of the proximal femur in a case of polyostotic fibrous dysplasia. Case Report: A 16 years old female case of polyostotic fibrous dysplasia had bilateral Shepherd’s crook deformity of the proximal femur with bilateral non – union of pathological fracture of neck femur. We managed each side in one stage with two osteotomies. On the right side, first oblique osteotomy was done from just distal to the greater trochanter up to the level of the neck and the second; lateral closing wedge abduction osteotomy was done at the subtrochanteric level. 2 months later on the left side double lateral closing wedge abduction osteotomies were performed both at the subtrochanteric level. Fixation of both the sides was done using a 135° Dynamic Richard’s screw with a long side plate to span the osteotomy sites and the lesion. Post – operatively we achieved a neck shaft angle of 135° on right side and 133° on the left side. Follow up imaging showed union at both the osteotomy sites bilaterally and also at the site of the pathological fracture of neck femur. Presently, at 18 months post – operatively, patient is walking full weight bearing without support and there are no signs of recurrence of lesions of fibrous dysplasia or the deformity. Conclusion: Double osteotomy is an easy and effective method to correct the shepherd’s crook deformity and achieve correct mechanical alignment. Dynamic hip screw with long side plate is a versatile implant to tackle the proximal femur deformity. Double osteotomy corrects the deformity and tackles the associated problems like non - union of the pathological neck femur fracture in one stage. PMID:27299066

Thiopurine Therapy Reduces the Incidence of Colorectal Neoplasia in Patients with Ulcerative Colitis. Data from the ENEIDA Registry.

PubMed

Gordillo, Jordi; Cabré, Eduard; Garcia-Planella, Esther; Ricart, Elena; Ber-Nieto, Yolanda; Márquez, Lucía; Rodríguez-Moranta, Francisco; Ponferrada, Ángel; Vera, Isabel; Gisbert, Javier P; Barrio, Jesús; Esteve, Maria; Merino, Olga; Muñoz, Fernando; Domènech, Eugeni

2015-12-01

Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC), but recent studies suggest a lower risk than previously reported. The aim was to evaluate the incidence of dysplasia, CRC and related risk factors in UC patients from a Spanish nationwide database. All UC patients were identified and retrospectively reviewed. Clinical-epidemiological data and the finding of dysplasia and/or CRC were collected. A total of 831 UC patients were included. Twenty-six cases of CRC in 26 patients and 29 cases of high-grade dysplasia (HGD) in 24 patients were found, accounting for 55 diagnoses of advanced neoplasia (AN = CRC and/or HGD) in 45 patients (33% of them within the first 8 years after UC diagnosis). The cumulative risk of AN was 2, 5.3 and 14.7% at 10, 20 and 30 years, respectively. Concomitant primary sclerosing cholangitis (odds ratio [OR] 10.90; 95% confidence interval [CI] 3.75-31.76, p < 0.001), extensive UC (OR 2.10, 95% CI 1.01-4.38, p = 0.048), UC diagnosis at an older age (OR 2.23, 95% CI 1.03-4.83, p = 0.043) and appendectomy prior to UC diagnosis (OR 2.66, 95% CI 1.06-6.71, p = 0.038) were independent risk factors for AN. Use of thiopurines (OR 0.21, 95% CI 0.06-0.74, p = 0.015) and being in a surveillance colonoscopy programme (OR 0.33; 95% CI 0.16-0.67; p = 0.002) were independent protective factors for AN. The risk of AN among UC patients is lower than previously reported but steadily increases from the time of UC diagnosis. The widespread use of thiopurines may have influenced this reduced incidence of UC-related neoplasias. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Surgical Management of Polyostotic Craniofacial Fibrous Dysplasia: Long-Term Outcomes and Predictors for Postoperative Regrowth

PubMed Central

Boyce, Alison M.; Burke, Andrea; Peck, Carolee Cutler; DuFresne, Craig R.; Lee, Janice S.; Collins, Michael T.

2017-01-01

Background The mainstay of treatment for craniofacial fibrous dysplasia is surgical; however, optimal indications and techniques are poorly understood, particularly in polyostotic disease and McCune-Albright syndrome. This study investigated surgical indications and risk factors for recurrence in a large cohort. Methods One hundred thirty-three craniofacial fibrous dysplasia subjects in a natural history study were evaluated. Radiographic studies, operative reports, and clinical records were reviewed. Results Thirty-six subjects underwent 103 craniofacial procedures (mean, 2.8 operations per subject), with 13.5 ± 10.5-year follow-up (range, 0 to 39 years). The most common indication was craniofacial deformity (n = 61 operations), including 36 initial operations (59 percent) and 26 reoperations (41 percent). Mean time to reoperation was 3.4 ± 3.2 years (range, 0.3 to 13.3 years). Re-growth occurred after 42 operations (68 percent), and was more frequent after operations in subjects with McCune-Albright syndrome growth hormone excess [22 of 25 operations (88 percent)] than without growth hormone excess [15 of 36 operations (58 percent); p = 0.02]. Of 11 subjects with growth hormone excess, nine (82 percent) were undiagnosed at the time of their initial operation. Regrowth was more frequent after debulking procedures [31 of 38 (82 percent)] than after more aggressive reconstructions [nine of 20 (45 percent); p = 0.007]. Eleven subjects underwent treatment for aneurysmal bone cysts, with recurrence in one subject. Eleven subjects underwent biopsies and none had complications or regrowth. Conclusions Craniofacial fibrous dysplasia regrowth and reoperation are common, particularly after debulking procedures. Outcomes are favorable for aneurysmal bone cysts and biopsies. McCune-Albright syndrome growth hormone excess is a risk factor for regrowth, and may be underdiagnosed in surgical patients. Surgeons should be aware of appropriate screening for endocrinopathies in fibrous dysplasia. These findings highlight the importance of a multidisciplinary approach to craniofacial fibrous dysplasia, and individualized care with long-term follow-up. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV. PMID:27219238

Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model.

PubMed

Saito, Akiko; Ooki, Akio; Nakamura, Takashi; Onodera, Shoko; Hayashi, Kamichika; Hasegawa, Daigo; Okudaira, Takahito; Watanabe, Katsuhito; Kato, Hiroshi; Onda, Takeshi; Watanabe, Akira; Kosaki, Kenjiro; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Sakamoto, Teruo; Yamaguchi, Akira; Sueishi, Kenji; Azuma, Toshifumi

2018-01-22

Runt-related transcription factor 2 (RUNX2) haploinsufficiency causes cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth, short stature, clavicular dysplasia, and osteoporosis. At present, as a therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC) transplantation therapy is performed in addition to drug therapy. However, MSC-based therapy for osteoporosis in CCD patients is difficult due to a reduction in the ability of MSCs to differentiate into osteoblasts resulting from impaired RUNX2 function. Here, we investigated whether induced pluripotent stem cells (iPSCs) properly differentiate into osteoblasts after repairing the RUNX2 mutation in iPSCs derived from CCD patients to establish normal iPSCs, and whether engraftment of osteoblasts derived from properly reverted iPSCs results in better regeneration in immunodeficient rat calvarial bone defect models. Two cases of CCD patient-derived induced pluripotent stem cells (CCD-iPSCs) were generated using retroviral vectors (OCT3/4, SOX2, KLF4, and c-MYC) or a Sendai virus SeVdp vector (KOSM302L). Reverted iPSCs were established using programmable nucleases, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-derived RNA-guided endonucleases, to correct mutations in CCD-iPSCs. The mRNA expressions of osteoblast-specific markers were analyzed using quantitative reverse-transcriptase polymerase chain reaction. iPSCs-derived osteoblasts were transplanted into rat calvarial bone defects, and bone regeneration was evaluated using microcomputed tomography analysis and histological analysis. Mutation analysis showed that both contained nonsense mutations: one at the very beginning of exon 1 and the other at the initial position of the nuclear matrix-targeting signal. The osteoblasts derived from CCD-iPSCs (CCD-OBs) expressed low levels of several osteoblast differentiation markers, and transplantation of these osteoblasts into calvarial bone defects created in rats with severe combined immunodeficiency showed poor regeneration. However, reverted iPSCs improved the abnormal osteoblast differentiation which resulted in much better engraftment into the rat calvarial bone defect. Taken together, these results demonstrate that patient-specific iPSC technology can not only provide a useful disease model to elucidate the role of RUNX2 in osteoblastic differentiation but also raises the tantalizing prospect that reverted iPSCs might provide a practical medical treatment for CCD.

FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting

PubMed Central

Riminucci, Mara; Collins, Michael T.; Fedarko, Neal S.; Cherman, Natasha; Corsi, Alessandro; White, Kenneth E.; Waguespack, Steven; Gupta, Anurag; Hannon, Tamara; Econs, Michael J.; Bianco, Paolo; Gehron Robey, Pamela

2003-01-01

FGF-23, a novel member of the FGF family, is the product of the gene mutated in autosomal dominant hypophosphatemic rickets (ADHR). FGF-23 has been proposed as a circulating factor causing renal phosphate wasting not only in ADHR (as a result of inadequate degradation), but also in tumor-induced osteomalacia (as a result of excess synthesis by tumor cells). Renal phosphate wasting occurs in approximately 50% of patients with McCune-Albright syndrome (MAS) and fibrous dysplasia of bone (FD), which result from postzygotic mutations of the GNAS1 gene. We found that FGF-23 is produced by normal and FD osteoprogenitors and bone-forming cells in vivo and in vitro. In situ hybridization analysis of FGF-23 mRNA expression identified “fibrous” cells, osteogenic cells, and cells associated with microvascular walls as specific cellular sources of FGF-23 in FD. Serum levels of FGF-23 were increased in FD/MAS patients compared with normal age-matched controls and significantly higher in FD/MAS patients with renal phosphate wasting compared with those without, and correlated with disease burden bone turnover markers commonly used to assess disease activity. Production of FGF-23 by FD tissue may play an important role in the renal phosphate–wasting syndrome associated with FD/MAS. PMID:12952917

Upper-extremity phocomelia reexamined: a longitudinal dysplasia.

PubMed

Goldfarb, Charles A; Manske, Paul R; Busa, Riccardo; Mills, Janith; Carter, Peter; Ezaki, Marybeth

2005-12-01

In contrast to longitudinal deficiencies, phocomelia is considered a transverse, intercalated segmental dysplasia. Most patients demonstrate severe, but not otherwise classifiable, upper-extremity deformities, which usually cannot be placed into one of three previously described phocomelia groups. Additionally, these phocomelic extremities do not demonstrate true segmental deficits; the limb is also abnormal proximal and distal to the segmental defect. The purpose of this investigation was to present evidence that upper-extremity abnormalities in patients previously diagnosed as having phocomelia in fact represent a proximal continuum of radial or ulnar longitudinal dysplasia. The charts and radiographs of forty-one patients (sixty extremities) diagnosed as having upper-extremity phocomelia were reviewed retrospectively. On the basis of the findings on the radiographs, the disorders were categorized into three groups: (1) proximal radial longitudinal dysplasia, which was characterized by an absent proximal part of the humerus, a nearly normal distal part of the humerus, a completely absent radius, and a radial-sided hand dysplasia; (2) proximal ulnar longitudinal dysplasia, characterized by a short one-bone upper extremity that bifurcated distally and by severe hand abnormalities compatible with ulnar dysplasia; and (3) severe combined dysplasia, with type A characterized by an absence of the forearm segment (i.e., the radius and ulna) and type B characterized by absence of the arm and forearm (i.e., the hand attached to the thorax). Twenty-nine limbs in sixteen patients could be classified as having proximal radial longitudinal dysplasia. Systemic medical conditions such as thrombocytopenia-absent radius syndrome were common in those patients, but additional musculoskeletal conditions were rare. Twenty limbs in seventeen patients could be classified as having proximal ulnar longitudinal dysplasia. Associated musculoskeletal abnormalities, such as proximal femoral focal deficiency, were common in those patients. Eleven limbs in ten patients were identified as having severe combined dysplasia, which was type A in seven of them and type B in four. Four patients with severe combined dysplasia had congenital cardiac anomalies, and four had associated musculoskeletal abnormalities. Three of the four patients with the type-B disorder had a contralateral ulnar longitudinal dysplasia. We propose that cases previously classified as upper-extremity phocomelia represent a spectrum of severe longitudinal dysplasia, as none of the sixty extremities that we studied demonstrated a true intercalary deficiency. These findings have both developmental and genetic implications.

Genetics Home Reference: progressive pseudorheumatoid dysplasia

MedlinePlus

... caused by mutations in the WISP3 gene. The function of the protein produced from this gene is not well understood, ... protein that may not function. Loss of WISP3 protein function likely disrupts normal cartilage maintenance and bone growth, ...

An unusual case of sciatic neuropraxia due to melorheostosis.

PubMed

Singh, Raj; Singh, Zile; Bala, Renu; Rana, Parveen; Sangwan, Sukhbir Singh

2010-12-01

Melorrheostosis is a rare osteosclerotic bone dysplasia of obscure etiology. The typical radiographic features are flowing candle wax, sub-periosteal bone and streaky endosteal bone formation in diaphyseal and epiphyseal area with sclerotomal pattern mainly involving appendicular skeleton. It is rarely associated with nerve palsies. The authors report a case of melorrheostotic mass causing sciatic neuropraxia and to the best of their knowledge it is the first case reported in the English language literature. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Subacute Sclerosing Panencephalitis in a Child with Human Immunodeficiency Virus Co-Infection

PubMed Central

Maurya, Pradeep Kumar; Thakkar, Mayur Deepak; Kulshreshtha, Dinkar; Singh, Ajai Kumar; Thacker, Anup Kumar

2016-01-01

Subacute sclerosing panencephalitis is a fatal infectious disease of childhood caused by persistence of the measles virus in the brain. The effect of human immunodeficiency virus (HIV) co-infection on subacute sclerosing panencephalitis remains elusive and rare. We report a child who developed subacute sclerosing panencephalitis following a short latency period and a rapidly progressive course with HIV co-infection. PMID:27777245

Occipitocervical fusion in skeletal dysplasia: a new surgical technique.

PubMed

Sitoula, Prakash; Mackenzie, William G; Shah, Suken A; Thacker, Mihir; Ditro, Colleen; Holmes, Laurens; Campbell, Jeffrey W; Rogers, Kenneth J

2014-07-01

Retrospective cohort study. This study describes clinical and radiological results of a new cable technique for occipitocervical fusion (OCF) in children with skeletal dysplasia (SD). Anatomical variability and poor bone quality make upper cervical surgery technically challenging in patients with SD. We present a new cable technique for OCF in children with SD when the posterior elements are not of a size or quality for other types of instrumentation. Retrospective review of 24 patients with SD (8 boys, 16 girls) who underwent OCF between 2001 and 2011. In this technique, cables provide compression across a bone graft that is prevented from entering the canal and the graft resists excessive lordosis. Demographic and radiographical data are presented. All patients were followed for initial outcomes of surgery, and 20 patients (83%) were followed for 2 years or more for mid- and long-term outcomes. Mean age at surgery was 6.5 years and mean follow-up was 4.1 ± 2.4 years. This technique was used as a primary procedure in 20 and a revision procedure in 4 patients. Diagnoses included Morquio syndrome (6), spondyloepiphyseal dysplasia (9), spondyloepimetaphyseal dysplasia (5), metatropic dysplasia (3), and Kniest syndrome (1). Ten patients had upper cervical instability and features of cervical myelopathy, and the remaining 14 patients had instability and signal changes on magnetic resonance image. Fusion extended from occiput to C2 in 71% patients, and upper cervical decompression was needed in 92% patients. Postoperatively, all patients were immobilized in a halo vest for mean duration of 12 weeks. Fusion was achieved in all patients. Complications included halo pin-tract infections (7), junctional instability (2), and extension of fusion (4). This new cable technique is a good alternative for OCF in patients with SD who have altered anatomy at the craniocervical junction not amenable to rigid internal fixation. 4.

Radiological and histological variants of thanatophoric dysplasia are associated with common mutations in FGFR-3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nerlich, A.G.; Freisinger, P.; Bonaventure, J.

1996-05-03

We describe two fetuses of the 21st week of gestation that share some macroscopic, radiologic, and histologic findings of thanatophoric dysplasia (TD), but also show distinct differences from the usual subtypes of TD. These differences mainly comprise the lack of facial abnormality, only mild reduction of chondrocyte proliferation and hypertrophy, and the lack of fibrous tissue interposition between cartilage and periosteal bone. Thus, these two cases may represent a distinct variant of thanatophoric dysplasia. The molecular analysis of the FGF-R-3 gene demonstrated in both cases mutations which were not significantly different from those of other cases of TD. Thus, themore » phenotypic modulation within the subtypes of TD may be influenced by additional and yet unknown factors. 16 refs., 4 figs., 1 tab.« less

Microcephaly, ectodermal dysplasia, multiple skeletal anomalies and distinctive facial appearance: delineation of cerebro-dermato-osseous-dysplasia.

PubMed

Castori, Marco; Pascolini, Giulia; Parisi, Valentina; Sana, Maria Elena; Novelli, Antonio; Nürnberg, Peter; Iascone, Maria; Grammatico, Paola

2015-04-01

In 1980, a novel multiple malformation syndrome has been described in a 17-year-old woman with micro- and turricephaly, intellectual disability, distinctive facial appearance, congenital atrichia, and multiple skeletal anomalies mainly affecting the limbs. Four further sporadic patients and a couple of affected sibs are also reported with a broad clinical variability. Here, we describe a 4-year-old girl strikingly resembling the original report. Phenotype comparison identified a recurrent pattern of multisystem features involving the central nervous system, and skin and bones in five sporadic patients (including ours), while the two sibs and a further sporadic case show significant phenotypic divergence. Marked clinical variability within the same entity versus syndrome splitting is discussed and the term "cerebro-dermato-osseous dysplasia" is introduced to define this condition. © 2015 Wiley Periodicals, Inc.

Expansive focal cemento-osseous dysplasia.

PubMed

Bulut, Emel Uzun; Acikgoz, Aydan; Ozan, Bora; Zengin, Ayse Zeynep; Gunhan, Omer

2012-01-01

To present a case of expansive focal cemento-osseous dysplasia and emphasize the importance of differential diagnosis. Cemento-osseous dysplasia is categorized into three subtypes on the basis of the clinical and radiographic features: Periapical, focal and florid. The focal type exhibits a single site of involvement in any tooth-bearing or edentulous area of the jaws. These lesions are usually asymptomatic; therefore, they are frequently diagnosed incidentally during routine radiographic examinations. Lesions are usually benign, show limited growth, and do not require further surgical intervention, but periodic follow-up is recommended because occasionally, this type of dysplasia progresses into florid osseous dysplasia and simple bone cysts are formed. A 24-year-old female patient was referred to our clinic for swelling in the left edentulous mandibular premolarmolar region and felt discomfort when she wore her prosthetics. She had no pain, tenderness or paresthesia. Clinical examination showed that the swelling in the posterior mandible that was firm, nonfluctuant and covered by normal mucosa. On panoramic radiography and computed tomography, a well defined lesion of approximately 1.5 cm in diameter of mixed density was observed. The swelling increased slightly in size over 2 years making it difficult to use prosthetics and, therefore, the lesion was totally excised under local anesthesia, and surgical specimens were submitted for histopathological examination. The histopathological diagnosis was focal cemento-osseous dysplasia. In the present case, because of the increasing size of the swelling making it difficult to use prosthetics, young age of the patient and localization of the lesion, in the initial examination, cemento-ossifying fibroma was suspected, and the lesion was excised surgically; the histopathological diagnosis confirmed it as focal cemento-osseous dysplasia. We present a case of expansive focal cemento-osseous dysplasia. Differential diagnosis is essential because ossifying fibroma is a real neoplastic entity.

Genetics Home Reference: primary sclerosing cholangitis

MedlinePlus

... with primary sclerosing cholangitis (PSC) in a southern European population. Dig Liver Dis. 2003 Aug;35(8): ... haplotypes in primary sclerosing cholangitis patients from five European populations. Tissue Antigens. 1999 May;53(5):459- ...

Monitoring dominant strictures in primary sclerosing cholangitis with brush cytology and FDG-PET.

PubMed

Sangfelt, Per; Sundin, Anders; Wanders, Alkwin; Rasmussen, Ib; Karlson, Britt-Marie; Bergquist, Annika; Rorsman, Fredrik

2014-12-01

Despite a high risk of cholangiocellular adenocarcinoma (CCA) it is unclear how surveillance of patients with primary sclerosing cholangitis (PSC) should be performed. We evaluated a follow-up algorithm of brush cytology and positron emission tomography/computed tomography with [(18)F] fluorodeoxyglucose ([(18)F]FDG-PET/CT), measured as maximum standardized uptake values, normalized to the liver background (SUVmax/liver) at 180 min, in PSC patients with dominant bile duct strictures. Brush cytology with high grade dysplasia (HGD) was detected in 12/70 patients (17%), yielding a diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 56%, 89%, 75%, and 88%, respectively. Preemptive liver transplantations due to repeated HGD before manifest CCA were performed in six patients. Receiver operating characteristic (ROC) analysis of [(18)F]FDG uptake showed that a SUVmax/liver quotient of 3.3 was able to discriminate between CCA and non-malignant disease with a sensitivity, specificity, PPV and NPV for CCA of 89%, 92%, 62%, 98%, respectively. A SUVmax/liver >3.3 detected CCA in 8/9 patients whereas a quotient <2.4 excluded CCA. Combining brush cytology and quantitative [(18)F]FDG-PET/CT yielded a sensitivity for HGD and/or CCA of 100% and a specificity of 88%. Early detection of HGD before manifest CCA is feasible with repeated brush cytology and may allow for preemptive liver transplantation. [(18)F]FDG-PET/CT has a high sensitivity for manifest CCA and a negative scan indicates a non-malignant state of the disease. Brush cytology and [(18)F]FDG-PET/CT are complementary in monitoring and managing PSC patients with dominant strictures. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

An S100P-positive biliary epithelial field is a preinvasive intraepithelial neoplasm in nodular-sclerosing cholangiocarcinoma.

PubMed

Nakanuma, Yasuni; Uchida, Tsuneyuki; Sato, Yasunori; Uesaka, Katsuhiko

2017-02-01

Nodular-sclerosing cholangiocarcinoma (NS-CCA) is a common CCA of the intrahepatic large, perihilar, and distal bile ducts. Intraepithelial biliary neoplasms, such as the mucosal extension of carcinoma and preinvasive neoplastic lesions (ie, biliary intraepithelial neoplasia) reportedly occur in the bile ducts around CCA. In the present study, we collectively refer to these intraepithelial lesions as "intraepithelial neoplasms of the bile duct (IENBs)". We examined the IENBs in 57 surgically resected cases of NS-CCA. S100P immunostaining was used to help detect IENBs. The IENBs formed field(s) of continuous neoplastic biliary epithelial cells and showed a flat, micropapillary, or papillotubular configuration. IENBs could be classified into 3 categories based on their atypia: group A (neoplastic but not enough for malignancy), B (neoplastic and sufficiently well differentiated for high-grade dysplasia), and C (overtly malignant and variably differentiated). IENB was found in 31 of 57 cases, with group C the most common (26 cases) followed by group B (22 cases) and group A (16 cases). The expression of cancer-related molecules and MIB-1 index of groups A and B differed from those of invasive CCA, whereas these features of group C were relatively similar to those of invasive CCA. In conclusion, IENB was not infrequently found in NS-CCA and could be classified into 3 grades. Preinvasive lesions (biliary intraepithelial neoplasias) are likely to be found in groups A and B, whereas cancerization would be included in group C. The classification of IENB may be useful for future studies of the preinvasive intraepithelial neoplastic lesions of NS-CCAs. Copyright © 2016. Published by Elsevier Inc.

Sclerosing Meningioma : Radiological and Clinical Characteristics of 21 Cases

PubMed Central

Kang, Ho; Se, Young-Bem; Dho, Yun-Sik; Choi, Seung Hong; Park, Sung-Hye

2016-01-01

Objective A rare subtype of meningioma, sclerosing meningioma is not included in the current World Health Organization classification of meningiomas and is classified into the category of other morphological variation subtypes. Sclerosing meningioma is often misdiagnosed to other non-benign meningioma or malignant neoplasm, so it is important to diagnose sclerosing type correctly. We analyzed the radiological and clinical characteristics of a series of sclerosing meningiomas. Methods Twenty-one patients who underwent surgery in one institute with a histopathologically proven sclerosing meningioma were included from 2006 to 2014. Eighteen tumors were diagnosed as a pure sclerosing-type meningioma, and 3 as mixed type. Magnetic resonance image was taken for all patients including contrast enhancement image. Computed tomography (CT) scan was taken for 16 patients. One neuroradiologist and 1 neurosurgeon reviewed all images retrospectively. Results In the all 16 patients with preoperative CT images, higher attenuation was observed in the meningioma than in the brain parenchyma, and calcification was observed in 11 (69%). In 15 of the 21 patients (71%), a distinctive very low signal intensity appeared as a dark color in T2-weighted images. Nine of these 15 tumors (60%) exhibited heterogeneous enhancement, and 6 (40%) exhibited homogeneous enhancement that was unlike the homogeneous enhancing pattern shown by conventional meningiomas. Ten patients had a clear tumor margin without peritumoral edema. Conclusion Although these peculiar radiological characteristics are not unique to sclerosing meningioma, we believe that they are distinctive features that may be helpful for distinguishing sclerosing meningioma from other subtypes. PMID:27847571

Melorheostosis and its treatment with intravenous zoledronic acid

PubMed Central

Hollick, Rosemary Jane; Black, Alison; Reid, David

2010-01-01

We report a case of melorheostosis, a rare bone disorder characterised by mesodermal dysplasia, and its successful and prolonged treatment with the intravenous bisphosphonate zoledronic acid. The middle-aged man presented with pain and swelling of his tibia, which was diagnosed by imaging and bone biopsy as being due to melorheostosis. There was early symptom control after a single infusion of intravenous zoledronic acid. Prolonged symptom relief was accompanied by long-term suppression of the bone resorption marker β cross-laps. We suggest that melorheostosis can be treated with intravenous zoledronic acid and that treatment can be monitored by the use of a specific bone resorption marker. PMID:22479293

Multicystic recurrence of hydrocele testis after sclerosing with polidocanol followed by spontaneous cure.

PubMed

Fariña, L A; Villavicencio, H

1995-01-01

Scrotal ultrasound has been used to confirm the resolution of hydrocele testis after sclerosing with different solutions, and so, early recurrences with a multicystic appearance were occasionally observed. This finding was considered a complication of the sclerosant treatment needing a surgical option [1]. We have observed that a multilocular recurrence of hydrocele after percutaneous sclerosing with polidocanol is frequently followed by spontaneous cure.

Subacute Sclerosing Panencephalitis in a Child with Human Immunodeficiency Virus Co-Infection.

PubMed

Maurya, Pradeep Kumar; Thakkar, Mayur Deepak; Kulshreshtha, Dinkar; Singh, Ajai Kumar; Thacker, Anup Kumar

2016-12-01

Subacute sclerosing panencephalitis is a fatal infectious disease of childhood caused by persistence of the measles virus in the brain. The effect of human immunodeficiency virus (HIV) co-infection on subacute sclerosing panencephalitis remains elusive and rare. We report a child who developed subacute sclerosing panencephalitis following a short latency period and a rapidly progressive course with HIV co-infection. © 2016 Marshfield Clinic.

Subacute sclerosing panencephalitis in a child with recurrent febrile seizures.

PubMed

Kartal, Ayşe; Çıtak Kurt, Ayşegül Neşe; Hirfanoğlu, Tuğba; Aydın, Kürşad; Serdaroğlu, Ayşe

2015-01-01

Subacute sclerosing panencephalitis (SSPE) is a devastating disease of the central nervous system (CNS) caused by persistent mutant measles virus infection. The diagnosis of SSPE is based on characteristic clinical and EEG findings and demonstration of elevated antibody titres against measles in cerebrospinal fluid. Subacute sclerosing panencephalitis can have atypical clinical features at the onset. Herein, we report an unusual case of subacute sclerosing panencephalitis in a child with recurrent febrile seizures. The disease progressed with an appearance of myoclonic jerks, periodic high amplitude generalized complexes on EEG, and elevated titers of measles antibodies in cerebrospinal fluid leading to the final diagnosis of subacute sclerosing panencephalitis.

Subacute Sclerosing Panencephalitis in a Child with Recurrent Febrile Seizures

PubMed Central

Kartal, Ayşe; Çıtak Kurt, Ayşegül Neşe; Hirfanoğlu, Tuğba; Aydın, Kürşad; Serdaroğlu, Ayşe

2015-01-01

Subacute sclerosing panencephalitis (SSPE) is a devastating disease of the central nervous system (CNS) caused by persistent mutant measles virus infection. The diagnosis of SSPE is based on characteristic clinical and EEG findings and demonstration of elevated antibody titres against measles in cerebrospinal fluid. Subacute sclerosing panencephalitis can have atypical clinical features at the onset. Herein, we report an unusual case of subacute sclerosing panencephalitis in a child with recurrent febrile seizures. The disease progressed with an appearance of myoclonic jerks, periodic high amplitude generalized complexes on EEG, and elevated titers of measles antibodies in cerebrospinal fluid leading to the final diagnosis of subacute sclerosing panencephalitis. PMID:25802788

A Study to Assess the Long-term Performance of SmartSet® HV and SmartSet® GHV Bone Cements in Primary Total Hip Replacement

ClinicalTrials.gov

2017-03-02

Rheumatoid Arthritis; Osteoarthritis; Post-traumatic Arthritis; Collagen Disorders; Avascular Necrosis; Traumatic Femoral Fractures; Nonunion of Femoral Fractures; Congenital Hip Dysplasia; Slipped Capital Femoral Epiphysis

Serial diffusion-weighted imaging in subacute sclerosing panencephalitis.

PubMed

Kanemura, Hideaki; Aihara, Masao

2008-06-01

Subacute sclerosing panencephalitis may be associated with clinical features of frontal lobe dysfunction. We previously reported that frontal lobe volume falls significantly as clinical stage progresses, using three-dimensional magnetic resonance imaging-based brain volumetry. The hypothesis that frontal volume increases correlate with clinical improvement, however, was not tested in our previous study. Therefore, we reevaluated our patient with subacute sclerosing panencephalitis, to determine whether apparent diffusion coefficient maps can characterize the clinical course of subacute sclerosing panencephalitis. We studied an 8-year-old boy with subacute sclerosing panencephalitis, using serial diffusion-weighted imaging magnetic resonance imaging, and measured the regional apparent diffusion coefficient. The regional apparent diffusion coefficient of the frontal lobe decreased significantly with clinical progression, whereas it increased to within normal range during clinical improvements. The apparent diffusion coefficient of the other regions did not change. These results suggest that the clinical signs of patients with subacute sclerosing panencephalitis are attributable to frontal lobe dysfunction, and that apparent diffusion coefficient measurements may be useful in predicting the clinical course of subacute sclerosing panencephalitis.

[Pneumococcal meningitis revealing dysplasia of the bony labyrinth in an infant].

PubMed

Louaib, D; François, M; Coderc, E; Dieu, S; Nathanson, M; Narcy, P; Gaudelus, J

1996-03-01

Dysplasias of the bony labyrinth are frequently associated with cerebrospinal fluid fistula and are usually discovered because of recurrent meningitis. A 1 year-old infant was admitted for a pneumococcal meningitis which appeared 2 days after the occurrence of a clear otorrhea from the right ear. The same organism was isolated from the otorrhea fluid, which also contained cerebrospinal fluid as confirmed cytochemically. The meningitis rapidly resolved with antibiotic treatment. Auditory brain stem responses were abolished from the right ear. CT of the temporal bones showed a pseudo-Mondini type labyrinth dysplasia at the right ear and Mondini type dysplasia at the left one. A translabyrinthine cerebrospinal fluid fistula was discovered by surgical exploration of the right ear, occurring through a perforation in the stapedial foot plate. The leak was cured by packing the vestibule and obturating both oval and round windows. Three years after the operation, the child did not experience any further episode of otorrhea or meningitis. Features suggesting a translabyrinthine fistula, especially otorrhea and deafness, should be systematically searched in any child with bacterial meningitis. Closure of these fistulas can prevent severe infectious recurrences.

Phenotypic expressions of a Gly154Arg mutation in type II collagen in two unrelated patients with spondyloepimetaphyseal dysplasia (SEMD)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaitila, I.; Marttinen, E.; Koerkkoe, J.

1996-05-03

Type II collagenopathies consist of chondrodysplasia ranging from lethal to mild in severity. A large number of mutations has been found in the COL2A1 gene. Glycine substitutions have been the most common types of mutation. Genotype-phenotype correlations in type II collagenopathies have not been established, partly because of insufficient clinical and radiographic description of the patients. We found a glycine-to-arginine substitution at position 154 in type II collagen in two unrelated isolated propositi with spondyloepimetaphyseal dysplasia and provide a comparative clinical and radiographic analysis from birth to young adulthood for this condition. The clinical phenotype was disproportionate short stature withmore » varus/valgus deformities of the lower limbs requiring corrective osteotomies, and lumbar lordosis. The skeletal radiographs showed an evolution from short tubular bones, delayed epiphyseal development, and mild vertebral involvement to severe metaphyseal dysplasia with dappling irregularities, and hip {open_quotes}dysplasia.{close_quotes} The metaphyseal abnormalities disappeared by adulthood. 27 refs., 11 figs., 1 tab.« less

Fatty metamorphosis and other patterns in fibrous dysplasia

PubMed Central

Shidham, Vinod B; Chavan, Ashwini; Rao, R Nagarjun; Komorowski, Richard A; Asma, Zeenath

2003-01-01

Background Interpretation of small biopsy fragments from suspected lesions of fibrous dysplasia with unusual clinical and / or radiological features may be challenging due to wide histomorphological spectrum of stromal appearances. Awareness of these variations should improve diagnostic confidence. Methods We retrospectively studied 26 cases of fibrous dysplasia (F- 19, M- 7; Ages ranged from 10 to 53 years) with confirmed diagnosis. The sites of the lesions were skull bones (9), humerus (1), femur (8), tibia (2), fibula (3), talus (1), mandible (1), and maxilla (1). Results Different stromal patterns, variably admixed with the classical pattern, were observed in 58%(15/26) of the cases. 20%(3/15) of these had more than one pattern. Focal fatty metamorphosis as groups of fat cells in the central portion of the lesion in the stroma of fibrous dysplasia between osseous trabeculae was observed in 23%(6/26) cases. Other patterns included myxoid stroma in 16%(4/26), collagenization of stroma in 12%(3/26), stroma rich pattern (with paucity of trabeculae) in 12%(3/26), foci of few foam cells in 23% (6/26), and calcified spherules in 12%(3/26). Focal osteoblastic rimming of trabeculae was observed only in 4%(1/26). Conclusions Various stromal variations and previously unreported fatty metamorphosis were frequently observed in fibrous dysplasia. PMID:12946277

Melorheostosis of the Foot: A Case Report of A rare entity with a Review of Multimodality Imaging Emphasizing the Importance of Conventional Radiography in Diagnosis.

PubMed

Ashish, Gulia; Shashikant, Juvekar; Ajay, Puri; Subhash, Desai

2016-01-01

Melorheostosis is a benign bone dysplasia affecting predominantly the appendicular skeleton and adjoining soft tissues. The diagnosis can be established on plain radiographs alone and advanced imaging modalities can be avoided. We hereby report a rare case of melorheostosis affecting the foot with a review of the role of various imaging modalities in diagnosis of this rare bone dysplasia. We present the case of a 29 years old man who was diagnosed with melorheostosis affecting his left foot. The patient presented to the outpatient department of our tertiary care referral hospital with complains of pain in the left ankle and foot with imaging and evaluation done at a primary center. The radiograph revealed an irregular, longitudinal extraosseous hyperostosis along the body of the calcaneum and the metacarpals which was consistent with the classical radiological description of melorheostosis. The CT, MRI and bone scan findings corroborated our primary diagnosis. The purpose of this case report is to review the features of this rare disorder affecting the foot, on multiple imaging modalities and emphasizing the role of conventional radiology in its diagnosis.

Melorheostosis of the Foot: A Case Report of A rare entity with a Review of Multimodality Imaging Emphasizing the Importance of Conventional Radiography in Diagnosis

PubMed Central

Ashish, Gulia; Shashikant, Juvekar; Ajay, Puri; Subhash, Desai

2016-01-01

Introduction: Melorheostosis is a benign bone dysplasia affecting predominantly the appendicular skeleton and adjoining soft tissues. The diagnosis can be established on plain radiographs alone and advanced imaging modalities can be avoided. We hereby report a rare case of melorheostosis affecting the foot with a review of the role of various imaging modalities in diagnosis of this rare bone dysplasia. Case Report: We present the case of a 29 years old man who was diagnosed with melorheostosis affecting his left foot. The patient presented to the outpatient department of our tertiary care referral hospital with complains of pain in the left ankle and foot with imaging and evaluation done at a primary center. The radiograph revealed an irregular, longitudinal extraosseous hyperostosis along the body of the calcaneum and the metacarpals which was consistent with the classical radiological description of melorheostosis. The CT, MRI and bone scan findings corroborated our primary diagnosis. Conclusion: The purpose of this case report is to review the features of this rare disorder affecting the foot, on multiple imaging modalities and emphasizing the role of conventional radiology in its diagnosis. PMID:27299136

Survey of subacute sclerosing panencephalitis in Japan.

PubMed

Abe, Yusaku; Hashimoto, Koichi; Iinuma, Kazuie; Ohtsuka, Yoko; Ichiyama, Takashi; Kusuhara, Koichi; Nomura, Keiko; Mizuguchi, Masashi; Aiba, Hideo; Suzuki, Yasuhiro; Mizusawa, Hidehiro; Hosoya, Mitsuaki

2012-12-01

Investigators conducted a retrospective epidemiological study of subacute sclerosing panencephalitis, a fatal disease caused by measles infection, over the past few years in Japan. Data on 118 cases obtained from a questionnaire sent to attending physicians were analyzed. The annual incidence of subacute sclerosing panencephalitis was approximately 0.03 cases per million from 2001 to 2005. Children infected with measles at a young age (<12 months) showed a high incidence of subacute sclerosing panencephalitis, and those infected before 6 months of age showed earlier onset. Because a positive correlation was found between the prevalence of measles and the onset of subacute sclerosing panencephalitis, particularly among children infected at an early age, it is vital to eradicate measles infection by vaccination.

Expression patterns of micro-RNAs 146a, 181a, and 155 in subacute sclerosing panencephalitis.

PubMed

Yiş, Uluç; Tüfekçi, Uğur Kemal; Genç, Şermin; Çarman, Kürşat Bora; Bayram, Erhan; Topçu, Yasemin; Kurul, Semra Hız

2015-01-01

Subacute sclerosing panencephalitis is caused by persistent brain infection of mutated virus, showing inflammation, neurodegeneration, and demyelination. Although many factors are emphasized in the pathogenesis of subacute sclerosing panencephalitis, the exact mechanism of neurodegeneration remains unknown. Micro-RNAs are small, noncoding RNAs that regulate gene expression at the posttranscriptional levels. Micro-RNAs are essential for normal immune system development; besides they are also implicated in the pathogenesis of many chronic inflammatory disorders. The aim of this study is to investigate the expression patterns of micro-RNAs 146a, 181a, and 155 in peripheral blood mononuclear cells of patients with subacute sclerosing panencephalitis. We enrolled 39 patients with subacute sclerosing panencephalitis and 41 healthy controls. Quantitative analysis of micro-RNAs 146a, 181a, and 155 were performed using specific stem-loop primers followed by real-time polymerase chain reaction. All of 3 micro-RNAs were upregulated in subacute sclerosing panencephalitis patients. In addition, the level of micro-RNA 155 expression was higher in stage 3 patients. But, micro-RNA 146a and 181a expression levels showed no association or correlation with clinically relevant data. Alteration of peripheral blood mononuclear cell micro-RNAs in subacute sclerosing panencephalitis may shed new light on the pathogenesis of disease and may contribute to the aberrant systemic rise in mRNA levels in subacute sclerosing panencephalitis. © The Author(s) 2014.

Zoledronic acid in pediatric metabolic bone disorders.

PubMed

Bowden, Sasigarn A; Mahan, John D

2017-10-01

Zoledronic acid (ZA), a highly potent intravenous bisphosphonate (BP), has been increasingly used in children with primary and secondary osteoporosis due to its convenience of shorter infusion time and less frequent dosing compared to pamidronate. Many studies have also demonstrated beneficial effects of ZA in other conditions such as hypercalcemia of malignancy, fibrous dysplasia (FD), chemotherapy-related osteonecrosis (ON) and metastatic bone disease. This review summarizes pharmacologic properties, mechanism of action, dosing regimen, and therapeutic outcomes of ZA in a variety of metabolic bone disorders in children. Several potential novel uses of ZA are also discussed. Safety concerns and adverse effects are also highlighted.

A "reverse" Maffucci's syndrome: case report and short review of the literature.

PubMed

Matzaroglou, Charalampos; Megas, Panagiotis; Panagiotopoulos, Elias; Notopoulos, Athanasios; Saridis, Alkis; Sourgiadaki, Efrosini; Koumoundourou, Dimitra; Dimakopoulos, Panagiotis

2005-01-01

Maffucci's syndrome is a congenital, non-hereditary mesodermal dysplasia associated with multiple enchondromas and after some years accompanied by hemangiomas. We describe a rare case of "reverse" Maffucci's syndrome in a 42-year-old woman who has suffered from multiple hemangiomas for the last 24 years. The last two years she complained for heel pain. Bone scintigraphic examination showed abnormal findings in the left calcaneal bone. The scintigraphy, radiology and histology findings revealed multiple enchondromas, so the diagnosis was changed into Maffucci's syndrome. After one year, the left calcaneal bone showed sarcomatous transformation.

[Bone dysplasia with dwarfism and diffuse skeletal alterations].

PubMed

Piussan, C; Maroteaux, P; Castroviejo, I; Risbourg, B

1975-01-01

Six cases of a new hereditary chondrodyplasia are reported. The features are severe dwarfism, generalized hypotonia, frequent and considerable desaxations of fingers and toes. Slight facial dysmorphism with evolutive scoliosis is often associated. Osteopetrosis is diffuse and is associated with important metaphyseal widening as well as epiphyseal irregularities and often carpal and tarsal supernumerary bones. No metabolic or chromosomal abnormality was found. The relations of the disease with related types described in Larsen's syndrome are considered.

Molecular pathology of bone tumours: diagnostic implications.

PubMed

Puls, Florian; Niblett, Angela J; Mangham, D Chas

2014-03-01

Alongside histomorphology and immunohistochemistry, molecular pathology is now established as one of the cornerstones in the tissue diagnosis of bone tumours. We describe the principal molecular pathological techniques employed, and each of the bone tumour entities where their identified characteristic molecular pathological changes can be detected to support and confirm the suspected histological diagnosis. Tumours discussed include fibrous dysplasia, classical and subtype osteosarcomas, central and surface cartilaginous tumours, Ewing's sarcoma, vascular tumours, aneurysmal bone cyst, chordoma, myoepithelioma, and angiomatoid fibrous histiocytoma. This is a rapidly evolving field with discoveries occurring every few months, and some of the newer entities (the Ewing's-like sarcomas), which are principally identified by their molecular pathology characteristics, are discussed. © 2013 John Wiley & Sons Ltd.

Midazolam or diazepam administration during electroencephalography helps to diagnose subacute sclerosing panencephalitis (SSPE).

PubMed

Yilmaz, Kutluhan; Sahin, Derya Aydin

2010-08-01

Although diagnostic contribution of intravenous diazepam administration during electroencephalography (EEG) recording in subacute sclerosing panencephalitis has been known, no another drug with less potential side effects has been studied in this procedure. In this study, diazepam is compared with midazolam in 25 subacute sclerosing panencephalitis-diagnosed children and 10 children with subacute sclerosing panencephalitis-suggesting symptoms, normal EEG findings and no certain diagnosis. Neither midazolam nor diazepam affected typical periodic slow-wave complexes. However, in the patients with atypical EEG abnormalities, midazolam, like diazepam, attenuated sharp or sharp-and-slow waves, and therefore made the identification of periodic slow-wave paroxysms easier. In the patients with normal EEGs, both midazolam and diazepam revealed typical periodic complexes on EEG recording in the same 3 patients. Cerebrospinal fluid examination verified the diagnosis of subacute sclerosing panencephalitis. The findings suggest that midazolam or diazepam administration increases the contribution of EEG recording in atypical cases with subacute sclerosing panencephalitis.

Bone mineral density before and after OLT: long-term follow-up and predictive factors.

PubMed

Guichelaar, Maureen M J; Kendall, Rebecca; Malinchoc, Michael; Hay, J Eileen

2006-09-01

Fracturing after liver transplantation (OLT) occurs due to the combination of preexisting low bone mineral density (BMD) and early posttransplant bone loss, the risk factors for which are poorly defined. The prevalence and predictive factors for hepatic osteopenia and osteoporosis, posttransplant bone loss, and subsequent bone gain were studied by the long-term posttransplant follow-up of 360 consecutive adult patients with end-stage primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Only 20% of patients with advanced PBC or PSC have normal bone mass. Risk factors for low spinal BMD are low body mass index, older age, postmenopausal status, muscle wasting, high alkaline phosphatase and low serum albumin. A high rate of spinal bone loss occurred in the first 4 posttransplant months (annual rate of 16%) especially in those with younger age, PSC, higher pretransplant bone density, no inflammatory bowel disease, shorter duration of liver disease, current smoking, and ongoing cholestasis at 4 months. Factors favoring spinal bone gain from 4 to 24 months after transplantation were lower baseline and/or 4-month bone density, premenopausal status, lower cumulative glucocorticoids, no ongoing cholestasis, and higher levels of vitamin D and parathyroid hormone. Bone mass therefore improves most in patients with lowest pretransplant BMD who undergo successful transplantation with normal hepatic function and improved gonadal and nutritional status. Patients transplanted most recently have improved bone mass before OLT, and although bone loss still occurs early after OLT, these patients also have a greater recovery in BMD over the years following OLT.

Management of symptomatic florid cemento-osseous dysplasia: Literature review and a case report

PubMed Central

Gucciardino, Federico; Rapetti, Roberta; Siervo, Sandro; Bianch, Andrea-Edoardo

2018-01-01

Introduction Cemento-osseous dysplasia is a jaw disorder characterized by a reactive process in which normal bone is replaced by connective tissue matrix. There are different Cemento-osseous dysplasia entities. The treatment of these lesions, once diagnosed by radiology, is not required because generally they are asymptomatic. The localization is in the tooth-bearing areas of the jaws and its distribution is symmetric. Case Reports In this case report, a 57-year-old Caucasian female patient was referred to our attention complaining of painful inflammatory events localized in the right angle of the jaw. The radiographic appearance, the distribution of several lesions and the positive vitality test of the involved teeth, supported the diagnosis of Florid Cemento-osseous dysplasia. Because of the symptomatology, the patient was submitted to surgery and the lesion and the second inferior right molar were removed. The histological examination of the specimens confirmed the diagnosis. Discussion Many lesions that may exhibit a similar sclerotic appearance on conventional radiographs have to be differentiated and dental imaging can be used to discriminate between Florid COD and other lesions. Diagnosis of Florid Cemento-osseous dysplasia can be made with accurate clinical and radiographic assessment. In asymptomatic cases no treatment is required and the patient should have regular follow-up, but in this symptomatic case it was necessary to proceed with surgical intervention. The surgery treatment in the symptomatic case had a favourable prognosis and the two years follow-up has shown a complete healing. Given the abow, it is concluded that the choice of treatment must be selective according to the disease sites. Key words:Cemento-ossifying dysplasia, fibro-osseous lesions, florid cemento-osseous dysplasia, cementoma. PMID:29721232

Management of symptomatic florid cemento-osseous dysplasia: Literature review and a case report.

PubMed

Aiuto, Riccardo; Gucciardino, Federico; Rapetti, Roberta; Siervo, Sandro; Bianch, Andrea-Edoardo

2018-03-01

Cemento-osseous dysplasia is a jaw disorder characterized by a reactive process in which normal bone is replaced by connective tissue matrix. There are different Cemento-osseous dysplasia entities. The treatment of these lesions, once diagnosed by radiology, is not required because generally they are asymptomatic. The localization is in the tooth-bearing areas of the jaws and its distribution is symmetric. In this case report, a 57-year-old Caucasian female patient was referred to our attention complaining of painful inflammatory events localized in the right angle of the jaw. The radiographic appearance, the distribution of several lesions and the positive vitality test of the involved teeth, supported the diagnosis of Florid Cemento-osseous dysplasia. Because of the symptomatology, the patient was submitted to surgery and the lesion and the second inferior right molar were removed. The histological examination of the specimens confirmed the diagnosis. Many lesions that may exhibit a similar sclerotic appearance on conventional radiographs have to be differentiated and dental imaging can be used to discriminate between Florid COD and other lesions. Diagnosis of Florid Cemento-osseous dysplasia can be made with accurate clinical and radiographic assessment. In asymptomatic cases no treatment is required and the patient should have regular follow-up, but in this symptomatic case it was necessary to proceed with surgical intervention. The surgery treatment in the symptomatic case had a favourable prognosis and the two years follow-up has shown a complete healing. Given the abow, it is concluded that the choice of treatment must be selective according to the disease sites. Key words: Cemento-ossifying dysplasia, fibro-osseous lesions, florid cemento-osseous dysplasia, cementoma.

McCune-Albright syndrome: radiological and MR findings.

PubMed

Yongjing, G; Huawei, L; Zilai, P; Bei, D; Hao, J; Kemin, C

2001-01-01

McCune-Albright syndrome (MAS) is a non-inherited disorder due to the GNAS1 gene mutation. The syndrome is characterized with the triad of polyostotic fibrous dysplasia, pigmented skin lesions, endocrinopathy, and precocious puberty. We report the case of a 14-year-old boy, presenting with sclerotic type of polyostotic fibrous dysplasia. Radiological methods including plain X-ray film, MR and whole body bone scintigraphy suggested the diagnosis of MAS. MRI provided more directly perceived images and it was more sensitive in demonstrating the lesion: its shape, contents, especially the size of the affected region. Histopathological study and the identification of mutant gene finally confirmed the diagnostic result.

Primary sclerosing cholangitis

PubMed Central

Silveira, Marina G; Lindor, Keith D

2008-01-01

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in end-stage liver disease and reduced life expectancy. PSC primarily affects young and middle-aged men, often in association with underlying inflammatory bowel disease. The etiology of PSC includes immune-mediated components and elements of undefined nature. A cholestatic picture of liver biochemistries with elevations in serum alkaline phosphatase, nonspecific autoantibodies such as perinuclear antineutrophilic antibody, antinuclear antibodies and smooth muscle antibodies, and diffuse multifocal biliary strictures, resulting in a ‘beaded’ appearance on radiographic studies, are the hallmarks of the disease. No effective medical therapy is currently available, although clinical studies are in progress. Ursodeoxycholic acid at high doses (28 mg/kg/day to 30 mg/kg/day) is the most promising agent but is unproven so far. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease, although recurrent disease can be observed in the transplanted liver. The multiple complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, peristomal varices, bacterial cholangitis, dominant biliary strictures, gallbladder stones and polyps, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of PSC. PMID:18701947

Melorheostosis causing lumbar radiculopathy: a case report and a review of the literature.

PubMed

Saxena, Ankur; Neelakantan, Asha; Jampana, Ravi; Sangra, Meharpal

2013-08-01

Melorheostosis is a rare sclerosing bone disorder with a predilection for the appendicular skeleton. Involvement of the spine is infrequent and largely asymptomatic. Surgical treatment for spinal involvement is therefore uncommon with only one reported case of lumbar fusion for painful lumbosacral melorheostosis. We report a case of lumbar melorheostosis causing disabling radiculopathy treated with nerve root decompression. Melorheostosis of the lumbar spine causing radicular symptoms has not been reported before. Our message from the management of this particular patient is to consider surgical option in symptomatic individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

Oral and maxillofacial sclerosing epithelioid fibrosarcoma: report of five cases.

PubMed

Folk, Gretchen S; Williams, Stephen B; Foss, Robert B; Fanburg-Smith, Julie C

2007-09-01

Sclerosing epithelioid fibrosarcoma (SEF) has distinctive morphology and occurs mainly in deep soft tissue of adult extremities. Approximately 59 cases of SEF have been reported, with only 12 previously described in head and neck locations. Lesions involving the oral and maxillofacial region (OMFR) and intraosseous examples are rare. We present five cases of OMFRSEF. The OMF Pathology Department Registry was searched for cases coded from 1990 to the present as "SEF," "fibrosarcoma not otherwise specified" or "neoplasm of uncertain histiogenesis." Inclusion required OMFR location, an abundantly sclerotic sarcoma with epithelioid features, and lack of other phenotype by immunohistochemistry. Five cases of SEF included 3 males and 2 females. The age of the patients were: 19, 22, 35, 47 and 47 years. Tumor location included the infra-temporal fossa, buccal mucosa (recurrence extending into bone), anterior mandible (intraosseous primary, focally extending into soft tissue), and left parotid and submandibular gland (with metaplastic bone) regions. Tumor sizes ranged from 1.0 to 5.7 cm, median 3.5 cm. Histologically, the tumors were well delineated and multinodular, separated by fibrous septae. The spindled to primarily epithelioid tumor cells formed moderately cellular sheets and cords of irregularly contoured medium to large, round to oval, occasionally overlapping nuclei, indistinct nucleoli, wispy eosinophilic (retracting) cytoplasm, and distinctive cytoplasmic borders, embedded in osteoid-like stroma. Hemangiopericytoid (HPC-like) vessels were observed. Despite numerous apoptotic cells, mitoses were generally low; necrosis was present in two cases. Three tumors were graded as 2/3 and two 1/3. Immunohistochemically, the tumor cells were positive for vimentin, 1 case focally for CD34, whereas all cases were negative for S100 protein, keratins, EMA, desmin, and SMA. Wide or radical excision was performed with no adjuvant therapy. Follow-up revealed that 4 cases recurred at a range of 12-120 months. One case had no recurrent/residual disease at 3 months. Metastatic disease was present in 2 cases, to chest wall and lumbar/thoracic spine at 12 and 21 months, respectively. One patient died of disease complications at 15 months. OMFRSEF occur in adults in various locations, but with a common propensity to involve bone; there is recurrent potential and morbidity with higher grade lesions. The differential diagnosis for these tumors in this site includes sclerosing carcinoma, Ewing/PNET, osteosarcoma, osteoblastoma, and benign and malignant myoepithelial salivary gland tumors. The collagen, focal spindle cell features, HPC-like vasculature, and weak focal CD34 reactivity in one case might have raised a possible relationship between OMFRSEF and low grade malignant solitary fibrous tumor, but the intraosseous propensity, epithelioid features and relative lack of CD34 make this a distinctive entity.

BILATERAL SUBRETINAL FLUID AND RETINAL VASCULOPATHY ASSOCIATED WITH SUBACUTE SCLEROSING PANENCEPHALITIS.

PubMed

Agarwal, Aniruddha; Singh, Ramandeep; Kumar, Abiraj; Dogra, Mangat R; Gupta, Amod

2017-01-01

To report a case of bilateral retinopathy associated with subacute sclerosing panencephalitis. History and clinical examination, fluorescein angiography, and optical coherence tomography. We report a rare case of unilateral, followed by bilateral retinopathy, subretinal fluid, and vasculopathy in a young boy. History of missed measles vaccination, behavioral and neurologic symptoms, and electroencephalogram suggested a diagnosis of subacute sclerosing panencephalitis. Retinal imaging using optical coherence tomography was performed to document changes in the retinal microstructure through the natural course of the disease. Within 8 weeks, the changes progressed to retinal atrophy in both eyes. The progressive course of retinitis associated with subacute sclerosing panencephalitis can be monitored on optical coherence tomography. Retinitis is subacute sclerosing panencephalitis rapidly progressive from the acute stage to the stage of atrophy, involving full thickness of the retina.

Pseudotumor cerebri secondary to subacute sclerosing panencephalitis.

PubMed

Ayçiçek, Ali; Işcan, Akin; Ceçe, Hasan

2009-05-01

Unusual presentations are not rare in subacute sclerosing panencephalitis. Five patients initially diagnosed with pseudotumor cerebri were ultimately determined to have pseudotumor cerebri secondary to subacute sclerosing panencephalitis. The present study retrospectively reviewed 56 cases history, neurologic symptoms, and clinical and laboratory data, as well as the outcomes. On admission, five patients (group 1) presenting with pseudotumor cerebri exhibited bilateral papilledema, and in each of them cranial magnetic resonance imaging revealed small lateral ventricles, effacement of the subarachnoid space, and no mass lesion. On admission, 51 patients (group 2) had no pseudotumor cerebri findings. The year of original measles infection, the interval between measles and onset of subacute sclerosing panencephalitis, and initial neurologic symptoms were similar, but length of symptoms before diagnosis of subacute sclerosing panencephalitis was shorter in group 1, and the clinical stage of subacute sclerosing panencephalitis on admission was more advanced in group 2. Cerebrospinal fluid mean open pressure was 378 +/- 22 H(2)O in group 1 and 146 +/- 28 H(2)O in group 2; cerebrospinal fluid antibody was 2038 +/- 768 U/L in group 1 and was 664 +/- 214 U/L in group 2. Only three of the five patients with pseudotumor cerebri had typical periodic discharges on electroencephalographic examination. These findings suggest that subacute sclerosing panencephalitis can cause pseudotumor cerebri.

Thyroid Hormone Receptor α Mutation Causes a Severe and Thyroxine-Resistant Skeletal Dysplasia in Female Mice

PubMed Central

Bassett, J. H. Duncan; Boyde, Alan; Zikmund, Tomas; Evans, Holly; Croucher, Peter I.; Zhu, Xuguang; Park, Jeong Won

2014-01-01

A new genetic disorder has been identified that results from mutation of THRA, encoding thyroid hormone receptor α1 (TRα1). Affected children have a high serum T3:T4 ratio and variable degrees of intellectual deficit and constipation but exhibit a consistently severe skeletal dysplasia. In an attempt to improve developmental delay and alleviate symptoms of hypothyroidism, patients are receiving varying doses and durations of T4 treatment, but responses have been inconsistent so far. Thra1PV/+ mice express a similar potent dominant-negative mutant TRα1 to affected individuals, and thus represent an excellent disease model. We hypothesized that Thra1PV/+ mice could be used to predict the skeletal outcome of human THRA mutations and determine whether prolonged treatment with a supraphysiological dose of T4 ameliorates the skeletal abnormalities. Adult female Thra1PV/+ mice had short stature, grossly abnormal bone morphology but normal bone strength despite high bone mass. Although T4 treatment suppressed TSH secretion, it had no effect on skeletal maturation, linear growth, or bone mineralization, thus demonstrating profound tissue resistance to thyroid hormone. Despite this, prolonged T4 treatment abnormally increased bone stiffness and strength, suggesting the potential for detrimental consequences in the long term. Our studies establish that TRα1 has an essential role in the developing and adult skeleton and predict that patients with different THRA mutations will display variable responses to T4 treatment, which depend on the severity of the causative mutation. PMID:24914936

Type and Level of RMRP Functional Impairment Predicts Phenotype in the Cartilage Hair Hypoplasia–Anauxetic Dysplasia Spectrum

PubMed Central

Thiel, Christian T. ; Mortier, Geert ; Kaitila, Ilkka ; Reis, André ; Rauch, Anita 

2007-01-01

Mutations in the RMRP gene lead to a wide spectrum of autosomal recessive skeletal dysplasias, ranging from the milder phenotypes metaphyseal dysplasia without hypotrichosis and cartilage hair hypoplasia (CHH) to the severe anauxetic dysplasia (AD). This clinical spectrum includes different degrees of short stature, hair hypoplasia, defective erythrogenesis, and immunodeficiency. The RMRP gene encodes the untranslated RNA component of the mitochondrial RNA–processing ribonuclease, RNase MRP. We recently demonstrated that mutations may affect both messenger RNA (mRNA) and ribosomal RNA (rRNA) cleavage and thus cell-cycle regulation and protein synthesis. To investigate the genotype-phenotype correlation, we analyzed the position and the functional effect of 13 mutations in patients with variable features of the CHH-AD spectrum. Those at the end of the spectrum include a novel patient with anauxetic dysplasia who was compound heterozygous for the null mutation g.254_263delCTCAGCGCGG and the mutation g.195C→T, which was previously described in patients with milder phenotypes. Mapping of nucleotide conservation to the two-dimensional structure of the RMRP gene revealed that disease-causing mutations either affect evolutionarily conserved nucleotides or are likely to alter secondary structure through mispairing in stem regions. In vitro testing of RNase MRP multiprotein-specific mRNA and rRNA cleavage of different mutations revealed a strong correlation between the decrease in rRNA cleavage in ribosomal assembly and the degree of bone dysplasia, whereas reduced mRNA cleavage, and thus cell-cycle impairment, predicts the presence of hair hypoplasia, immunodeficiency, and hematological abnormalities and thus increased cancer risk. PMID:17701897

Melorheostosis with occlusion of dorsalis pedis artery.

PubMed

Ishibe, Motomi; Inoue, Masayuki; Saitou, Katsutoshi

2002-02-01

Melorheostosis is an unusual sclerotic dysplasia of bone. The case of a 51-year-old female patient with melorheostosis and occlusion of the dorsalis pedis artery is described. Although numerous vascular anomalies have been noted in patients with melorheostosis, occlusion of the dorsalis pedis artery has not been reported previously.

Zoledronic acid in pediatric metabolic bone disorders

PubMed Central

Mahan, John D.

2017-01-01

Zoledronic acid (ZA), a highly potent intravenous bisphosphonate (BP), has been increasingly used in children with primary and secondary osteoporosis due to its convenience of shorter infusion time and less frequent dosing compared to pamidronate. Many studies have also demonstrated beneficial effects of ZA in other conditions such as hypercalcemia of malignancy, fibrous dysplasia (FD), chemotherapy-related osteonecrosis (ON) and metastatic bone disease. This review summarizes pharmacologic properties, mechanism of action, dosing regimen, and therapeutic outcomes of ZA in a variety of metabolic bone disorders in children. Several potential novel uses of ZA are also discussed. Safety concerns and adverse effects are also highlighted. PMID:29184807

Bulbous epiphysis and popcorn calcification as related to growth plate differentiation in osteogenesis imperfecta.

PubMed

Brizola, Evelise; McCarthy, Edward; Shapiro, Jay Robert

2015-01-01

Osteogenesis Imperfecta (OI) is an heritable systemic disorder of connective tissue due to different sequence variants in genes affecting both the synthesis of type I collagen and osteoblast function. Dominant and recessive inheritance is recognized. Approximately 90% of the OI cases are due to mutations in COL1A1/A2 genes. We clinically and radiologically describes an adult male with type III osteogenesis imperfecta who presents a rare bone dysplasia termed bulbous epiphyseal deformity in association with popcorn calcifications. Popcorn calcifications may occur with bulbous epiphyseal deformity or independently. Molecular analysis was performed for COL1A1, COL1A2, LEPRE1 and WNT1 genes. An uncommon COL1A1 mutation was identified. Clinical and radiological exams confirmed a distinctive bulbous epiphyseal deformity with popcorn calcifications in distal femurs. We have identified four additional OI patients reported in current literature, whose X-rays show bulbous epiphyseal deformity related to mutations in CR-TAP, LEPRE1 and WNT1 genes. The mutation identified here had been previously described twice in OI patients and no previous correlation with bulbous epiphyseal deformity was described. The occurrence of this bone dysplasia focuses attention on alterations in normal growth plate differentiation and the subsequent effect on endochondral bone formation in OI.

A Recurrence of Bilateral Diffuse Sclerosing Lobular Hyperplasia of Breast: A Case Report.

PubMed

Elfituri, Osama; Sonawane, Snehal; Xu, Haoliang; Warso, Michael A; Wiley, Elizabeth

2017-12-01

Mammary sclerosing lobular hyperplasia is an uncommon benign fibroproliferative lesion of adolescent and young women, often of African American heritage with an incidence of ~3%. Patients generally complain of a palpable, painless, or slightly tender and well-defined lump in breast. Very rarely, this lesion may be bilateral and diffuse. The definitive diagnosis of sclerosing lobular hyperplasia requires histopathologic evaluation. Here, we describe a case of diffuse sclerosing lobular hyperplasia in a 29-year-old African American woman that required bilateral mastectomy and recurred bilaterally requiring second resections. This appears to be the first report of this phenomenon.

Congenital oval or round window anomaly with or without abnormal facial nerve course: surgical results for 15 ears.

PubMed

Thomeer, Henricus; Kunst, Henricus; Verbist, Berit; Cremers, Cor

2012-07-01

To describe the audiometric results in a consecutive series of patients with congenital ossicular aplasia (Class 4a) or dysplasia of the oval and/or round window (Class 4b), which might include a possible anomalous course of the facial nerve. Retrospective chart study. Tertiary referral center. A tertiary referral center study with a total of 14 patients with congenital minor ear anomalies as part of a consecutive series (n = 89) who underwent exploratory tympanotomies (15 ears). Audiometric results. In 8 of 15 ears, ossicular reconstruction was attempted. In the short term (1 mo), there was a serviceable hearing outcome (air-bone gap closure to within 25 dB) in 4 ears. However, the long-term results showed deterioration because of an increased air-bone gap in all but 1 ear. No facial nerve lesion was observed postoperatively. Congenital dysplasia or aplasia of the oval and/or round window is an uncommon congenital minor ear anomaly. Classical microsurgical opportunities are rare in this group of anomalies. Newer options for hearing rehabilitation, such as the osseointegrated passive bone conduction devices, have become viable alternatives for conventional air conduction hearing devices. In the near future, upcoming active bone conduction devices might become the most preferred surgical option. In cases in which the facial nerve is only partially overlying the oval window, a type of malleostapedotomy procedure might result in a serviceable postoperative hearing level.

Cemento-ossifying fibroma of the maxilla.

PubMed

Al-Shaham, A A; Samher, A A

2010-12-01

Despite the fact that cemento-ossifying fibromas of the maxilla may be quite large and locally aggressive, en-bloc excision is achieved by gentle blunt dissection, with the whole tumour mass peeled out from the adjacent structures. Until recently different fibro-osseous tumours that contained cementum were classified together as "cementomas". In 1992 The World Health Organization adopted a new classification that included these fibromas as benign osseous tumours. While such tumours of the mandible are common, those of the maxilla are rare. They are growth products of periodontal membrane remnant. The triggering mechanism in the formation of cementum outside the periodontal membrane remains unclear. We present a 35-year-old woman who had a giant expanding lobular mass in the right maxilla of 5 years duration. She had visual disturbances and nasal obstruction, and was treated successfully by surgical en-bloc resection of the tumour through an infraorbital transverse incision. The differential diagnosis included fibrous dysplasia, osteoid osteoma, osteoblastoma, chronic sclerosing osteomyelitis, ameloblastoma, squamous cell carcinoma of the maxillary sinus, calcifying epithelial odontogenic tumour (Pindborg tumour) and calcifying odontogenic cyst (Gorlin cyst). Histopathological examination confirmed a cemento-ossifying fibroma.

Subacute sclerosing panencephalitis presenting as schizophrenia with an alpha coma pattern in a child.

PubMed

Kartal, Ayşe; Kurt, Ayşegül Neşe Çitak; Gürkaş, Esra; Aydin, Kurşad; Serdaroğlu, Ayşe

2014-10-01

Subacute sclerosing panencephalitis, a progressive neurodegenerative disorder of the central nervous system, can present atypically with uncharacteristic electroencephalographic (EEG) features at its onset albeit typically with progressive mental deterioration, behavioral changes, and myoclonic jerks. An atypical presentation of subacute sclerosing panencephalitis can lead to a delay in diagnosis, thus hindering early treatment. Herein, we describe a 14-year-old girl who presented with insomnia, amnesia, auditory and visual hallucinations. The patient's electroencephalography on admission showed an alpha coma pattern. In spite of antipsychiatric treatment (olanzapine 20 mg/d) for 3 months, a progressive deterioration in neurologic function was observed. Subacute sclerosing panencephalitis was suspected and diagnosis was confirmed by increased titers of measles antibodies in the cerebrospinal fluid. The attention of pediatricians should be drawn to psychiatric symptoms as possible initial presentations of subacute sclerosing panencephalitis in order to avoid needless diagnostic and treatment procedures. © The Author(s) 2013.

Mandibuloacral dysplasia: A premature ageing disease with aspects of physiological ageing.

PubMed

Cenni, Vittoria; D'Apice, Maria Rosaria; Garagnani, Paolo; Columbaro, Marta; Novelli, Giuseppe; Franceschi, Claudio; Lattanzi, Giovanna

2018-03-01

Mandibuloacral dysplasia (MAD) is a rare genetic condition characterized by bone abnormalities including localized osteolysis and generalized osteoporosis, skin pigmentation, lipodystrophic signs and mildly accelerated ageing. The molecular defects associated with MAD are mutations in LMNA or ZMPSTE24 (FACE1) gene, causing type A or type B MAD, respectively. Downstream of LMNA or ZMPSTE24 mutations, the lamin A precursor, prelamin A, is accumulated in cells and affects chromatin dynamics and stress response. A new form of mandibuloacral dysplasia has been recently associated with mutations in POLD1 gene, encoding DNA polymerase delta, a major player in DNA replication. Of note, involvement of prelamin A in chromatin dynamics and recruitment of DNA repair factors has been also determined under physiological conditions, at the border between stress response and cellular senescence. Here, we review current knowledge on MAD clinical and pathogenetic aspects and highlight aspects typical of physiological ageing. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A gene for cleidocranial dysplasia to the short arm of chromosome 6

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feldman, G.F.; Muenke, M.; Robin, N.H.

1995-04-01

Cleidocranial dysplasia (CCD) is an autosomal dominant generalized bone dysplasia characterized by mild-to-moderate short stature, clavicular aplasia or hypoplasia, supernumerary and ectopic teeth, delayed eruption of secondary teeth, a characteristic craniofacial appearance, and a variety of other skeletal anomalies. We have performed linkage studies in five families with CCD, with 24 affected and 20 unaffected individuals, using microsatellite markers spanning two candidate regions on chromosomes 8q and 6. The strongest support for linkage was with chromosome 6p microsatellite marker D6S282 with a two-point lod score of 4.84 ({theta} = .03). Furthermore, the multipoint lod score was 5.70 in the intervalmore » between D6S282 and D6S291. These data show that the gene for autosomal dominant CCD is located within a 19-cM interval on the short arm of chromosome 6, between D6S282 and D6S291. 25 refs., 3 figs., 1 tab.« less

Fibroblast growth factor receptor signaling crosstalk in skeletogenesis.

PubMed

Miraoui, Hichem; Marie, Pierre J

2010-11-02

Fibroblast growth factors (FGFs) play important roles in the control of embryonic and postnatal skeletal development by activating signaling through FGF receptors (FGFRs). Germline gain-of-function mutations in FGFR constitutively activate FGFR signaling, causing chondrocyte and osteoblast dysfunctions that result in skeletal dysplasias. Crosstalk between the FGFR pathway and other signaling cascades controls skeletal precursor cell differentiation. Genetic analyses revealed that the interplay of WNT and FGFR1 determines the fate and differentiation of mesenchymal stem cells during mouse craniofacial skeletogenesis. Additionally, interactions between FGFR signaling and other receptor tyrosine kinase networks, such as those mediated by the epidermal growth factor receptor and platelet-derived growth factor receptor α, were associated with excessive osteoblast differentiation and bone formation in the human skeletal dysplasia called craniosynostosis, which is a disorder of skull development. We review the roles of FGFR signaling and its crosstalk with other pathways in controlling skeletal cell fate and discuss how this crosstalk could be pharmacologically targeted to correct the abnormal cell phenotype in skeletal dysplasias caused by aberrant FGFR signaling.

Chronic inflammation triggered by the NLRP3 inflammasome in myeloid cells promotes growth plate dysplasia by mesenchymal cells.

PubMed

Wang, Chun; Xu, Can-Xin; Alippe, Yael; Qu, Chao; Xiao, Jianqiu; Schipani, Ernestina; Civitelli, Roberto; Abu-Amer, Yousef; Mbalaviele, Gabriel

2017-07-07

Skeletal complications are common features of neonatal-onset multisystem inflammatory disease (NOMID), a disorder caused by NLRP3-activating mutations. NOMID mice in which NLRP3 is activated globally exhibit several characteristics of the human disease, including systemic inflammation and cartilage dysplasia, but the mechanisms of skeletal manifestations remain unknown. In this study, we find that activation of NLRP3 in myeloid cells, but not mesenchymal cells triggers chronic inflammation, which ultimately, causes growth plate and epiphyseal dysplasia in mice. These responses are IL-1 signaling-dependent, but independent of PARP1, which also functions downstream of NLRP3 and regulates skeletal homeostasis. Mechanistically, inflammation causes severe anemia and hypoxia in the bone environment, yet down-regulates the HIF-1α pathway in chondrocytes, thereby promoting the demise of these cells. Thus, activation of NLRP3 in hematopoietic cells initiates IL-1β-driven paracrine cascades, which promote abnormal growth plate development in NOMID mice.

An analysis of 72% chromated glycerin used for sclerotherapy: sterility, potency, and cost after extended shelf life.

PubMed

Ghaznavi, Amir M; Nakamura, Mio; Tepper, Donna

2015-01-01

Sclerotherapy is the treatment of reticular veins and telangiectasias of the lower extremities. Sclerosants destroy endothelial tissue and expose subendothelial collagen fibers, which lead to subsequent fibrosis of vessels, thus preventing recanalization. There are several available sclerosants including sodium tetradecyl sulfate (STS), polidocanol (POL), and chromated glycerin (CG) with varying efficacy, potency, side effect profile, and cost. To identify the possible bacterial contamination and potency of CG beyond the current recommended shelf life of 3 months and to prove if CG is as cost effective as other available sclerosants. Samples of 72% CG underwent bacterial endotoxin, sterility, and potency analysis at Days 0, 24, and 183. In addition, cost comparison was performed with other commercially available sclerosants including STS and POL. No samples of CG showed any bacterial contamination. All aliquots of glycerin remained sterile at Day 14. Potency at Day 24 was 99.2%, which was the same at Day 183. Cost comparison with other sclerosants revealed that CG is lower cost per milliliter than STS and POL. Seventy-two percent CG has no contamination and maintains its reported potency up to 6 months while comparable with the cost of other commercially available sclerosants.

Resected case of eosinophilic cholangiopathy presenting with secondary sclerosing cholangitis

PubMed Central

Miura, Fumihiko; Asano, Takehide; Amano, Hodaka; Yoshida, Masahiro; Toyota, Naoyuki; Wada, Keita; Kato, Kenichiro; Takada, Tadahiro; Fukushima, Junichi; Kondo, Fukuo; Takikawa, Hajime

2009-01-01

Eosinophilic cholangiopathy is a rare condition characterized by eosinophilic infiltration of the biliary tract and causes sclerosing cholangitis. We report a patient with secondary sclerosing cholangitis with eosinophilic cholecystitis. A 46-year-old Japanese man was admitted to our hospital with jaundice. Computed tomography revealed dilatation of both the intrahepatic and extrahepatic bile ducts, diffuse thickening of the wall of the extrahepatic bile duct, and thickening of the gallbladder wall. Under the diagnosis of lower bile duct carcinoma, he underwent pylorus-preserving pancreatoduodenectomy and liver biopsy. On histopathological examination, conspicuous fibrosis was seen in the lower bile duct wall. In the gallbladder wall, marked eosinophilic infiltration was seen. Liver biopsy revealed mild portal fibrosis. He was diagnosed as definite eosinophilic cholecystitis with sclerosing cholangitis with unknown etiology. The possible etiology of sclerosing cholangitis was consequent fibrosis from previous eosinophilic infiltration in the bile duct. The clinicopathological findings of our case and a literature review indicated that eosinophilic cholangiopathy could cause a condition mimicking primary sclerosing cholangitis (PSC). Bile duct wall thickening in patients with eosinophilic cholangitis might be due to fibrosis of the bile duct wall. Eosinophilic cholangiopathy might be confused as PSC with eosinophilia. PMID:19294772

Oral Rehabilitation of a Patient With Ectodermal Dysplasia Treated With Fresh-Frozen Bone Allografts and Computer-Guided Implant Placement: A Clinical Case Report.

PubMed

Maiorana, Carlo; Poli, Pier Paolo; Poggio, Carlo; Barbieri, Paola; Beretta, Mario

2017-05-01

Ectodermal dysplasia (ED) is an inherited disorder characterized by abnormality of ectodermally derived structures. A recurrent oral finding is oligodontia, which in turn leads to a severely hypotrophic alveolar process with typical knife-edge morphology and adverse ridge contours. This unfavorable anatomy can seriously hamper proper implant placement. Fresh-frozen bone (FFB) allografts recently have been proposed to augment the residual bone volume for implant placement purposes; however, scientific evidence concerning the use of FFB to treat ED patients is absent. Similarly, data reporting computer-aided template-guided implant placement in medically compromised patients are limited. Thus the purpose of this report is to illustrate the oral rehabilitation of a female patient affected by ED and treated with appositional FFB block grafts and consecutive computer-guided flapless implant placement in a 2-stage procedure. Fixed implant-supported dental prostheses were finally delivered to the patient, which improved her self-esteem and quality of life. During the follow-up recall 1 year after the prosthetic loading, the clinical examination showed healthy peri-implant soft tissues with no signs of bleeding on probing or pathologic probing depths. The panoramic radiograph confirmed the clinical stability of the result. Peri-implant marginal bone levels were radiographically stable with neither pathologic bone loss at the mesial and distal aspects of each implant nor peri-implant radiolucency. Within the limitations of this report, the use of FFB allografts in association with computer-aided flapless implant surgery might be considered a useful technique in patients affected by ED. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Pathology of orbital bones. The XXXII Edward Jackson Memorial Lecture.

PubMed

Blodi, F C

1976-01-01

The orbital bones may show nearly all the pathologic changes observed in the skull and in the face. The congenital anomalies in this area are numerous and involve various forms of craniostenoses. Among the benign osseous tumors the osteoma is most frequently encountered in the orbit. Fibrous dysplasia is a tumefaction of indeterminate behavior that often involves the orbit. Osteosarcoma or other malignant neoplasms are rarely seen in this area. Eosinophilic granuloma and Hand-Schüller-Christian disease are tumor-like lesions that may involve the orbit.

Detection of extensive melorheostosis on bone scintigram performed for suspected metastases.

PubMed

Sonoda, Luke I; Halim, Mohamed Y; Balan, Kottekkattu K

2011-03-01

Melorheostosis is a rare but benign disorder characterized by asymmetric osteosclerotic dysplasia. Radiographic appearances are characteristic and described as "melting wax flowing down a candle." This disorder may involve more than one bone contiguously across the joints following a sclerotomal distribution. It is often asymptomatic but occasionally presents with pain and contractures. The authors report accidental detection of bilateral upper and lower limb melorheostosis in an elderly woman with the history of breast cancer and recent onset of low back pain, which was referred for a bone scintigram for suspected metastases. The images showed bilateral femoral and tibial melorheostosis, which was subsequently confirmed on plain radiograph and by clinical follow-up.

Use of mini dental implants in ectodermal dysplasia children: follow-up of three cases.

PubMed

Sfeir, E; Nassif, N; Moukarzel, C

2014-07-01

Ectodermal dysplasia is a hereditary genodermatosis characterised by a congenital defect of ectodermal structures, causing tooth malformations and anomalies. Implantology has become accepted in these subjects. However cases are often complicated by a reduction in the size of the alveolar process, making the insertion of conventional implants difficult without bone grafting. The reduced diameter of mini-implants and their ease of insertion provide an interesting solution in supporting removable or fixed prosthesis. The purpose of this paper is to report the follow-up of three cases of children (11-12 year- old) with ectodermal dysplasia in which mini-implants were used to support the prostheses. In the first case, two mini-implants were inserted into the anterior part of the mandible for stabilising a removable denture (2 years follow-up). In the other two cases, mini- implants were inserted in the maxilla and mandible to replace missing front teeth with fixed prostheses. Patients were called for follow- up every 6 months: in the sencod case follow-up lasted 4 years in the mandible and 2 years in the maxilla; in the third case, 2 years in the maxilla and 1 year in the mandible. The use of mini-implants in children with ectodermal dysplasia can enhance aesthetics, and functional and psychosocial development.

Balloon-occluded Retrograde Transvenous Obliteration (BRTO): Technique and Intraprocedural Imaging

PubMed Central

Sabri, Saher S.; Saad, Wael E. A.

2011-01-01

Balloon-occluded retrograde transvenous obliteration (BRTO) is an endovascular technique used as a therapeutic adjunct or alternative to transjugular intrahepatic shunts (TIPS) in the management of gastric varices. Occlusion balloons are strategically placed to modulate flow within the gastrorenal or gastrocaval shunt to allow stagnation of the sclerosant material within the gastric varix. The approach and complexity of the procedure depends on the anatomic classification of inflow and outflow veins of the varix. Ethanolamine oleate has been described as the main sclerosant used in this procedure. Recently, foam sclerosants have gained popularity as alternative embolization agents, which provide the advantage of better variceal wall contact and potentially less dose of sclerosant. PMID:22942548

Generation of sclerosant foams by mechanical methods increases the foam temperature.

PubMed

Tan, Lulu; Wong, Kaichung; Connor, David; Fakhim, Babak; Behnia, Masud; Parsi, Kurosh

2017-08-01

Objective To investigate the effect of agitation on foam temperature. Methods Sodium tetradecyl sulphate and polidocanol were used. Prior to foam generation, the sclerosant and all constituent equipment were cooled to 4-25℃ and compared with cooling the sclerosant only. Foam was generated using a modified Tessari method. During foam agitation, the temperature change was measured using a thermocouple for 120 s. Results Pre-cooling all the constituent equipment resulted in a cooler foam in comparison with only cooling the sclerosant. A starting temperature of 4℃ produced average foam temperatures of 12.5 and 13.2℃ for sodium tetradecyl sulphate and polidocanol, respectively. It was also found that only cooling the liquid sclerosant provided minimal cooling to the final foam temperature, with the temperature 20 and 20.5℃ for sodium tetradecyl sulphate and polidocanol, respectively. Conclusion The foam generation process has a noticeable impact on final foam temperature and needs to be taken into consideration when creating foam.

Degenrative Fibroid and Sclerosing Peritonitis

PubMed Central

Critchley, Michael; Bagley, John; Iqbal, Pervis

2012-01-01

Sclerosing peritonitis is a rare condition characterised by ascites, peritoneal and bowel wall thickening. Causes reported in the literature include luteal ovarian the comas, peritoneal dialysis, peritoneal chemotherapy and liver cirrhosis. We report an interesting case of a woman presenting with diarrhoea, abdominal distension, ascites and pleural effusion. She was subsequently diagnosed with Sclerosing Peritonitis caused by a degenerating fibroid which was successfully treated by Total Abdominal Hysterectomy and Bilateral Salpingoophrectomy. PMID:22928130

Further expansion of the mutational spectrum of spondylo-meta-epiphyseal dysplasia with abnormal calcification.

PubMed

Ürel-Demir, Gizem; Simsek-Kiper, Pelin Ozlem; Akgün-Doğan, Özlem; Göçmen, Rahşan; Wang, Zheng; Matsumoto, Naomichi; Miyake, Noriko; Utine, Gülen Eda; Nishimura, Gen; Ikegawa, Shiro; Boduroglu, Koray

2018-06-08

Spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type, is a rare autosomal recessive disorder of the skeleton characterized by disproportionate short stature with narrow chest and dysmorphic facial features. The skeletal manifestations include platyspondyly, short flared ribs, short tubular bones with abnormal metaphyses and epiphyses, severe brachydactyly, and premature stippled calcifications in the cartilage. The abnormal calcifications are so distinctive as to point to the definitive diagnosis. However, they may be too subtle to attract diagnostic attention in infancy. Homozygous variants in DDR2 cause this disorder. We report on a 5-year-old girl with the classic phenotype of SMED, SL-AC in whom a novel homozygous nonsense mutation in DDR2 was detected using exome sequencing.

Histological examination and clinical evaluation of the jawbone of an adult patient with cleidocranial dysplasia: a case report

PubMed Central

Schnutenhaus, Sigmar; Luthardt, Ralph G; Rudolph, Heike; Götz, Werner

2015-01-01

Objectives: Cleidocranial dysplasia (CCD) is a rare congenital malformation syndrome, inherited autosomal-dominantly. During a course of treatment including surgical, implantological and restorative procedures, an opportunity arose to histologically examine biopsies of the maxilla and mandible of a CCD patient 47 years of age. Case report: The aim of this case report is to present the results of the histological evaluation of the alveolar bone and the surgical pretreatment for and placement of six implants each in the maxilla and the mandible. The implants were inserted in a minimally invasive procedure using 3D template guidance. Following uneventful healing of the implants, ceramically veneered bridges were cemented on individual titanium abutments. Since the patient had not received orthodontic treatment in childhood-which would have been the treatment modality of choice-this implantological and prosthodontic approach was necessary. Biopsies were taken from the maxilla and the mandible before placing the implants. Histological evaluation showed bone with strong, coarsely interconnecting trabeculae, especially in the maxilla. Both the bone and the gingiva otherwise exhibited a normal structure without pathological features or anomalies. Conclusion: The clinical parameters and histological evaluation of this one clinical case suggest that the concepts familiar from general oral implantology in terms of surgical and prosthetic procedures can be adopted for older patients with CCD. PMID:26339428

Bulbous epiphysis and popcorn calcification as related to growth plate differentiation in osteogenesis imperfecta

PubMed Central

Brizola, Evelise; McCarthy, Edward; Shapiro, Jay Robert

2015-01-01

Summary Background Osteogenesis Imperfecta (OI) is an heritable systemic disorder of connective tissue due to different sequence variants in genes affecting both the synthesis of type I collagen and osteoblast function. Dominant and recessive inheritance is recognized. Approximately 90% of the OI cases are due to mutations in COL1A1/A2 genes. We clinically and radiologically describes an adult male with type III osteogenesis imperfecta who presents a rare bone dysplasia termed bulbous epiphyseal deformity in association with popcorn calcifications. Popcorn calcifications may occur with bulbous epiphyseal deformity or independently. Methods Molecular analysis was performed for COL1A1, COL1A2, LEPRE1 and WNT1 genes. Results An uncommon COL1A1 mutation was identified. Clinical and radiological exams confirmed a distinctive bulbous epiphyseal deformity with popcorn calcifications in distal femurs. We have identified four additional OI patients reported in current literature, whose X-rays show bulbous epiphyseal deformity related to mutations in CR-TAP, LEPRE1 and WNT1 genes. Conclusion The mutation identified here had been previously described twice in OI patients and no previous correlation with bulbous epiphyseal deformity was described. The occurrence of this bone dysplasia focuses attention on alterations in normal growth plate differentiation and the subsequent effect on endochondral bone formation in OI. PMID:26604951

Clinical and radiographic features of solitary and cemento-osseous dysplasia-associated simple bone cysts.

PubMed

Chadwick, J W; Alsufyani, N A; Lam, E W N

2011-05-01

The simple bone cyst (SBC) is a pseudocyst that can occur as a solitary entity in the jaws or may occur in association with cemento-osseous dysplasia (COD). The purpose of this study was to review the clinical and radiographic features of solitary and COD-associated SBCs. Archived imaging reports from the Special Procedures Clinic in Oral and Maxillofacial Radiology at the Faculty of Dentistry at the University of Toronto between 1 January 1989 and 31 December 2009 revealed 23 COD-associated SBCs and 68 solitary SBCs. Almost all solitary and COD-associated SBCs were found in the mandible. Furthermore, 87.0% of COD-associated SBCs were found in females in their fifth decade of life (P < 0.001) while solitary SBCs were found in equal numbers in both sexes in their second decade of life (P < 0.005). COD-associated SBCs were also more likely to cause thinning of the endosteal cortex, bone expansion and scalloping of the superior border between teeth (all P < 0.001) than solitary SBCs that are classically described as having these characteristics. Finally, COD-associated SBC demonstrated a loss of lamina dura more often (P < 0.05) than solitary SBCs. Knowledge of the sporadic association between COD and SBC and their potential radiographic appearances should prevent inappropriate treatment and management of these patients.

A simple technique to strengthen the initial and mid-term to long-term stability of the cup during total hip arthroplasty in developmental dysplasia of the hip.

PubMed

Guan, Mingqiang; Zhou, Guanming; Li, Xue

2018-04-01

To assess the effects of a technique of cup blocking screws combined with impaction bone grafting during total hip arthroplasty (THA) for patients with developmental dysplasia of the hip (DDH). From August 2011 to July 2015, 53 patients (59 hips) with DDH in our hospital were treated with THA using the technique of cup blocking screws combined with impaction particulate bone grafting. These patients were prospectively followed, and the clinical and imaging results were collected. Harris hip score (HHS) was raised from 41.24 before surgery to 91.49 at the latest follow-up (p less than 0.001). Length discrepancy (LLD) was reduced from 28.97 mm before surgery to 6.08 mm after surgery (p less than 0.001). No loosening of the cup was detected at the last follow-up. The differences were insignificant in cup inclination and rate of cup coverage among the 3 groups of Crowe type II, type III, and type IV DDH (p greater than 0.05). The technique of cup blocking screws combined with impaction particulate bone grafting is simple and reliable, and it not only simplifies the attainment of initial stability, but also strengthens the mid-term to long-term stability during THA in DDH.

Window classification of brain CT images in biomedical articles.

PubMed

Xue, Zhiyun; Antani, Sameer; Long, L Rodney; Demner-Fushman, Dina; Thoma, George R

2012-01-01

Effective capability to search biomedical articles based on visual properties of article images may significantly augment information retrieval in the future. In this paper, we present a new method to classify the window setting types of brain CT images. Windowing is a technique frequently used in the evaluation of CT scans, and is used to enhance contrast for the particular tissue or abnormality type being evaluated. In particular, it provides radiologists with an enhanced view of certain types of cranial abnormalities, such as the skull lesions and bone dysplasia which are usually examined using the " bone window" setting and illustrated in biomedical articles using "bone window images". Due to the inherent large variations of images among articles, it is important that the proposed method is robust. Our algorithm attained 90% accuracy in classifying images as bone window or non-bone window in a 210 image data set.

Postzygotic HRAS mutation causing both keratinocytic epidermal nevus and thymoma and associated with bone dysplasia and hypophosphatemia due to elevated FGF23.

PubMed

Avitan-Hersh, Emily; Tatur, Sameh; Indelman, Margarita; Gepstein, Vardit; Shreter, Roni; Hershkovitz, Dov; Brick, Riva; Bergman, Reuven; Tiosano, Dov

2014-01-01

Epidermal nevus syndrome is a rare group of disorders characterized by the combination of congenital epidermal nevi and extracutaneous features, including skeletal, neurological, ocular, and other systemic findings. We report a case of keratinocytic epidermal nevus syndrome that includes a thymoma, bone dysplasia, and hypophosphatemia with elevated fibroblast growth factor 23 (FGF23) levels associated with postzygotic HRAS mutation. A 14-year-old boy was admitted due to recent limping. The physical examination revealed multiple right-sided linear epidermal nevi along Blaschko's lines. Magnetic resonance imaging showed cystic lesions in cervical bones and thymoma, and x-ray examination showed cystic lesions in the hands. Biochemical studies demonstrated severe hypophosphatemia, normocalcemia, high normal PTH, low 25-hydroxyvitamin D and low 1,25-dihydroxyvitamin D levels. The serum FGF23 C-terminal level was normal, but the intact FGF23 level was found to be elevated. Genetic evaluation revealed a heterozygote mutation in the HRAS gene in both the keratinocytic epidermal nevus and thymoma but not in DNA extracted from blood lymphocytes, thus establishing the mutation as postzygotic. Postzygotic mutations in HRAS lead to elevation of FGF23 levels, as found in mutated PHEX, FGF23, DMP1, and ENPP1 genes, which lead to hypophosphatemia. An identical postzygotic HRAS mutation was shown to be present in both keratinocytic epidermal nevus and thymoma and to be associated with bone lesions and hypophosphatemia due to elevated FGF23 levels. These may all be related to the HRAS mutation.

Melorheostosis: a rare entity: a case report.

PubMed

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease.

Melorheostosis: a rare entity: a case report

PubMed Central

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease. PMID:25489356

Restoration of Oral Function for Adult Edentulous Patients with Ectodermal Dysplasia: A Prospective Preliminary Clinical Study.

PubMed

Wu, Yiqun; Wang, Xu Dong; Wang, Feng; Huang, Wei; Zhang, Zhiyong; Zhang, Zhiyuan; Kaigler, Darnell; Zou, Duohong

2015-10-01

Therapy with zygomatic implants (ZIs) or conventional implants (CIs) has proven to be an effective method to restore oral function for systemically healthy patients. However, it is still a major challenge to fully restore oral function to edentulous adult patients with ectodermal dysplasia (ED). The aim of this study was to determine an effective treatment protocol for restoring oral function using ZIs and CIs to edentulous adult ED patients. Ten edentulous adult ED patients were treated in this study. The treatment protocol involved the following: (1) bone augmentation in the region of the anterior teeth; (2) placement of two ZIs and four CIs in the maxilla, and four CIs in the mandible; (3) fabrication of dental prosthesis; and (4) psychological and oral education. Following treatment of these patients, implant success rates, biological complications, patient satisfaction, and psychological changes were recorded. Although there was evidence of bone graft resorption in the maxilla, bone augmentation of the mandible was successful in all patients. Nine CIs in the maxilla failed and were removed. All ZIs were successful, and the CIs success rates were 77.50% in the maxilla and 100% in the mandible, with a mean of 88.75%. The mean peri-implant bone resorption for the CIs ranged from 1.3 ± 0.4 mm to 1.8 ± 0.6 mm, and four cases exhibited gingival hyperplasia in the maxilla and mandible. One hundred percent of the patients were satisfied with the restoration of their oral function, and >50% of the patients exhibited enhanced self-confidence and self-esteem. This study demonstrates that oral function can be restored in edentulous adult ED patients using a comprehensive and systematic treatment protocol involving psychological and oral education, bone augmentation, implant placement, and denture fabrication. Despite these positive outcomes, bone augmentation remains challenging in the anterior region of the maxilla for edentulous adult ED patients. © 2015 Wiley Periodicals, Inc.

Bilateral optic neuritis--the only ocular finding in a case of subacute sclerosing panencephalitis.

PubMed

Ozer, Pinar Altiaylik; Ozkan, Mehpare; Sekeroglu, Hande Taylan; Kadayifcilar, Sibel; Yuksel, Deniz; Aksoy, Ayse

2014-02-01

Subacute sclerosing panencephalitis is a rare disease of central nervous system caused by defective measles virus. Chorioretinitis with macular involvement is the mostly observed ocular finding in the disease. Other reported ocular findings in the disease are cortical blindness, hemianopsia, nystagmus, extraocular muscle paresis and optic atrophy. We present a rare case of subacute sclerosing panencephalitis with isolated bilateral optic neuritis as the only ocular finding without macular involvement.

Mineral Oil-induced Sclerosing Lipogranuloma of the Penis

PubMed Central

Bjurlin, Marc A.; Carlsen, Jens; Grevious, Mark; Jordan, Michael D.; Taylor, Aisha; Divakaruni, Naveen

2010-01-01

Sclerosing lipogranuloma of the penis results from injection of high viscosity fluid for the purpose of penile augmentation and may have devastating cosmetic and sexual function consequences. Although rare, sclerosing lipogranuloma should be considered in the differential diagnosis of subcutaneous induration or nodules of the male genitalia as it may mimic carcinoma and poses a diagnostic challenge in patients reluctant to admit to injection therapy. Surgical excision with penile reconstruction is the mainstay of treatment. The authors present a case of a 35-year-old Myanmarese man with a sclerosing lipogranuloma of the penis due to injection of mineral oil successfully managed with penile biopsy and excision with split-thickness skin graft phalloplasty and provide a review of the current literature. PMID:20877525

The Use of Patient-Specific Induced Pluripotent Stem Cells (iPSCs) to Identify Osteoclast Defects in Rare Genetic Bone Disorders

PubMed Central

Chen, I-Ping

2014-01-01

More than 500 rare genetic bone disorders have been described, but for many of them only limited treatment options are available. Challenges for studying these bone diseases come from a lack of suitable animal models and unavailability of skeletal tissues for studies. Effectors for skeletal abnormalities of bone disorders may be abnormal bone formation directed by osteoblasts or anomalous bone resorption by osteoclasts, or both. Patient-specific induced pluripotent stem cells (iPSCs) can be generated from somatic cells of various tissue sources and in theory can be differentiated into any desired cell type. However, successful differentiation of hiPSCs into functional bone cells is still a challenge. Our group focuses on the use of human iPSCs (hiPSCs) to identify osteoclast defects in craniometaphyseal dysplasia. In this review, we describe the impact of stem cell technology on research for better treatment of such disorders, the generation of hiPSCs from patients with rare genetic bone disorders and current protocols for differentiating hiPSCs into osteoclasts. PMID:25621177

Novel developments in foam sclerotherapy: Focus on Varithena® (polidocanol endovenous microfoam) in the management of varicose veins.

PubMed

Star, Phoebe; Connor, David E; Parsi, Kurosh

2018-04-01

Scope Varithena® is a recently approved commercially available drug/delivery unit that produces foam using 1% polidocanol for the management of varicose veins. The purpose of this review is to examine the benefits of foam sclerotherapy, features of the ideal foam sclerosant and the strengths and limitations of Varithena® in the context of current foam sclerotherapy practices. Method Electronic databases including PubMed, Medline (Ovid) SP as well as trial registries and product information sheets were searched using the keywords, 'Varithena', 'Varisolve', 'polidocanol endovenous microfoam', 'polidocanol' and/or 'foam sclerotherapy/sclerosant'. Articles published prior to 20 September 2016 were identified. Results Foam sclerosants have effectively replaced liquid agents due to their physiochemical properties resulting in better clinical outcomes. Medical practitioners commonly prepare sclerosant foam at the bedside by agitating liquid sclerosant with a gas such as room air, using techniques as described by Tessari or the double syringe method. Such physician-compounded foams are highly operator dependent producing inconsistent foams of different gas/liquid compositions, bubble size, foam behaviour and varied safety profiles. Varithena® overcomes the variability and inconsistencies of physician-compounded foam. However, Varithena® has limited applications due to its fixed sclerosant type and concentration, cost and lack of worldwide availability. Clinical trials of Varithena® have demonstrated efficacy and safety outcomes equivalent or better than physician-compounded foam but only in comparison to placebo alone. Conclusion Varithena® is a promising step towards the creation of an ideal sclerosant foam. Further assessment in independent randomised controlled clinical trials is required to establish the advantages of Varithena® over and above the current best practice physician-compounded foam.

Genetic mapping of a locus for multiple ephiphyseal dysplasia (EDM2) to a region of chromosome 1 containing a type IX collagen gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Briggs, M.D.; Choi, HiChang; Warman, M.L.

1994-10-01

Multiple epiphyseal dysplasia (MED) is a dominantly inherited chondrodysplasia characterized by mild short stature and early-onset osteoarthrosis. Some forms of MED clinically resemble another chondrodysplasia phenotype, the mild form of pseudoachondroplasia (PSACH). On the basis of their clinical similarities as well as similar ultra-structural and biochemical features in cartilage from some patients, it has been proposed that MED and PSACH belong to a single bone-dysplasia family. Recently, both mild and severe PSACH as well as a form of MED have been linked to the same interval on chromosome 19, suggesting that they may be allelic disorders. Linkage studies with themore » chromosome 19 markers were carried out in a large family with MED and excluded the previously identified interval. Using this family, we have identified a MED locus on the short arm of chromosome 1, in a region containing the gene (COL9A2) that encodes the {alpha}2 chain of type IX collagen, a structural component of the cartilage extracellular matrix. 39 refs., 3 figs., 3 tabs.« less

An evaluation of neuropeptide Y status in subacute sclerosing panencephalitis patients.

PubMed

Abuhandan, M; Calik, M; Almaz, V; Taskın, A; Cakmak, A; Selek, S

2013-01-01

This study aimed to evaluate the neuropeptide Y values of patients with subacute sclerosing panencephalitis. The study comprised 38 patients diagnosed with subacute sclerosing panencephalitis at our clinic, who were being routinely followed-up, together with a control group of 36. Using the Risk and Haddad classification for clinical staging, 16 patients were determined as Stage II and 22 patients as Stage III. Neuropeptide Y values were measured by Enzyme Immunoassay methods. The neuropeptide Y values of the all patients with subacute sclerosing panencephalitis were found to be significantly high compared to the control group (p<0.01). The neuropeptide Y values of the Stage III group were found to be significantly high compared to the Stage II and control groups (p<0.05). The neuropeptide Y values of the Stage II group were not determined to be significant compared to the control group (p≤0.05). Neuropeptide Y can be considered a useful parameter to confirm diagnosis at advanced stages and to establish differences between stages in patients with subacute sclerosing panencephalitis.

Identification of Genetic Co-Modifiers in Shwachman-Diamond Syndrome

DTIC Science & Technology

2013-03-01

abnormalities, pancreatic insufficient, and bone marrow failure.5 Neutropenia characterizes the primary defect in SDS, however, the degree of... neutropenia can fluctuate and panctyopenia commonly occurs. Skeletal defects (e.g. metaphyseal dysplasia or polydactyly) are associated with lower numbers of...Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia . Experience of the

Clinical significance of increased serum levels of FGF-23 in fibrous dysplasia.

PubMed

Florez, Helena; Mandelikova, Stanislava; Filella, Xavier; Monegal, Ana; Guañabens, Núria; Peris, Pilar

2017-12-30

Fibrous dysplasia (FD) can be associated with the development of hypophosphatemic osteomalacia, caused by the production of FGF-23 by dysplastic bone tissue. This study analysed FGF-23 levels in patients with FD, and their association with disease activity and serum phosphate values. Twelve adult patients with FD were included in the study. Clinical history, disease extension and activity and treatments received were reviewed, and the relationship of those values with FGF-23 and serum P levels was analysed. FGF-23 was elevated in 6/12 patients (50%). Patients with high FGF-23 levels had similar age and disease activity and extension than those who did not. No differences were observed in serum phosphate values between both groups (increased FGF-23: 3.9±0.9 mg/dl vs. decreased FGF-23: 3.5±0.6 mg/dl). In fact, none of the patients with increased FGF-23 had low serum phosphate values. Adult FD patients frequently present elevated FGF-23 values with no serum phosphate level repercussion, suggesting an alteration in the processing of this protein in the dysplastic bone tissue for this pathology. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism.

PubMed

Su, W C; Kitagawa, M; Xue, N; Xie, B; Garofalo, S; Cho, J; Deng, C; Horton, W A; Fu, X Y

1997-03-20

The achondroplasia class of chondrodysplasias comprises the most common genetic forms of dwarfism in humans and includes achondroplasia, hypochondroplasia and thanatophoric dysplasia types I and II (TDI and TDII), which are caused by different mutations in a fibroblast growth-factor receptor FGFR3 (ref. 1). The molecular mechanism and the mediators of these FGFR3-related growth abnormalities are not known. Here we show that mutant TDII FGFR3 has a constitutive tyrosine kinase activity which can specifically activate the transcription factor Stat1 (for signal transducer and activator of transcription). Furthermore, expression of TDII FGFR3 induced nuclear translocation of Stat1, expression of the cell-cycle inhibitor p21(WAF1/CIP1), and growth arrest of the cell. Thus, TDII FGFR3 may use Stat1 as a mediator of growth retardation in bone development. Consistent with this, Stat1 activation and increased p21(WAF1/CIP1) expression was found in the cartilage cells from the TDII fetus, but not in those from the normal fetus. Thus, abnormal STAT activation and p21(WAF1/CIP1) expression by the TDII mutant receptor may be responsible for this FGFR3-related bone disease.

Bilateral sclerosing orbital pseudotumour in an adult

PubMed Central

Sripathi, Smiti; Shenoy, Poonam Mohan; Ayachit, Anurag; Kadavigere, Rajagopal

2014-01-01

Sclerosing pseudotumour of the orbit is a rare idiopathic chronic inflammatory process, which greatly mimics neoplasms both clinically and on imaging studies. It is therefore important to differentiate this entity from true neoplasms and to rule out any systemic associations. We present a rare case of sclerosing orbital pseudotumour in an adult man with no systemic illnesses who presented with painless progressive proptosis of both eyes and showed a gradual initial response to steroid therapy but relapsed after a 2-year interval. PMID:24876210

Bilateral sclerosing orbital pseudotumour in an adult.

PubMed

Sripathi, Smiti; Shenoy, Poonam Mohan; Ayachit, Anurag; Kadavigere, Rajagopal

2014-05-29

Sclerosing pseudotumour of the orbit is a rare idiopathic chronic inflammatory process, which greatly mimics neoplasms both clinically and on imaging studies. It is therefore important to differentiate this entity from true neoplasms and to rule out any systemic associations. We present a rare case of sclerosing orbital pseudotumour in an adult man with no systemic illnesses who presented with painless progressive proptosis of both eyes and showed a gradual initial response to steroid therapy but relapsed after a 2-year interval. 2014 BMJ Publishing Group Ltd.

Dental Perspectives in Fibrous Dysplasia and McCune-Albright Syndrome

PubMed Central

Akintoye, Sunday O.; Boyce, Alison M.; Collins, Michael T.

2013-01-01

McCune-Albright syndrome (MAS) is a rare multisystem disorder characterized by the triad of polyostotic fibrous dysplasia (PFD), endocrine disorders and café-au-lait skin pigmentation. Ninety percent of MAS patients have FD lesions in the craniofacial area, resulting in significant orofacial deformity, dental disorders, bone pain and compromised oral health. Maxillo-mandibular FD is also associated with dental developmental disorders, malocclusion, and high caries index. There is limited data on the outcomes of dental treatments in maxillo-mandibular FD/MAS patients, because clinicians and researchers have limited access to patients, and there are concerns that dental surgery may activate quiescent jaw FD lesions to grow aggressively. This report highlights current perspectives on dental management issues associated with maxillo-mandibular FD within the context of MAS. PMID:23953425

Imaging in the diagnosis of cemento-ossifying fibroma: a case series.

PubMed

Mithra, R; Baskaran, Pavitra; Sathyakumar, M

2012-01-01

Cemento-ossifying fibroma is a benign fibro-osseous lesion belonging to the same category as fibrous dysplasia and cementifying dysplasia. These are slow-growing lesions that are seen in the third and fourth decades of life. Both the ossifying fibroma and cemento-ossifying fibroma represent two extremes of the same disease process since histologically both contain bone and cementum. However, the term cemento-ossifying fibroma is justified on the basis of clinical and radiological correlation. Radiographs have become an essential tool in the diagnosis of lesions in the jaw, where the anatomy is complex. Nowadays, CT provides information for diagnosis as well as treatment planning. In this case series, we report three cases of cemento-ossifying fibroma that were histologically confirmed and discuss the imaging findings.

Peripheral osteoma, compound odontoma, focal cemento-osseous dysplasia, and cemento-ossifying fibroma in the same hemimandible: CBCT findings of an unusual case.

PubMed

Borghesi, Andrea; Tonni, Ingrid; Pezzotti, Stefania; Maroldi, Roberto

2017-12-01

Peripheral osteoma is the most common subtype of osteoma that arises most frequently in the craniofacial bones. It may occur at any age with a male-to-female ratio of 2:1. Peripheral osteoma may affect the mandible, particularly the ramus and the condyle. Compound odontoma is a subtype of odontoma that occurs in young subjects without gender predilection. It affects the maxilla more frequently than the mandible. Focal cemento-osseous dysplasia and cemento-ossifying fibroma are 2 benign fibro-osseous lesions with a female predominance that occur most commonly in the posterior region of the mandible. We report the first case involving the simultaneous occurrence of these 4 benign lesions in the same hemimandible diagnosed by CBCT.

Imaging in the Diagnosis of Cemento-Ossifying Fibroma: A Case Series

PubMed Central

Mithra, R; Baskaran, Pavitra; Sathyakumar, M

2012-01-01

Cemento-ossifying fibroma is a benign fibro-osseous lesion belonging to the same category as fibrous dysplasia and cementifying dysplasia. These are slow-growing lesions that are seen in the third and fourth decades of life. Both the ossifying fibroma and cemento-ossifying fibroma represent two extremes of the same disease process since histologically both contain bone and cementum. However, the term cemento-ossifying fibroma is justified on the basis of clinical and radiological correlation. Radiographs have become an essential tool in the diagnosis of lesions in the jaw, where the anatomy is complex. Nowadays, CT provides information for diagnosis as well as treatment planning. In this case series, we report three cases of cemento-ossifying fibroma that were histologically confirmed and discuss the imaging findings. PMID:23029635

Bone structure in two adult subjects with impaired minor spliceosome function resulting from RNU4ATAC mutations causing microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1).

PubMed

Krøigård, Anne Bruun; Frost, Morten; Larsen, Martin Jakob; Ousager, Lilian Bomme; Frederiksen, Anja Lisbeth

2016-11-01

Microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1), or Taybi-Linder syndrome is characterized by distinctive skeletal dysplasia, severe intrauterine and postnatal growth retardation, microcephaly, dysmorphic features, and neurological malformations. It is an autosomal recessive disorder caused by homozygous or compound heterozygous mutations in the RNU4ATAC gene resulting in impaired function of the minor spliceosome. Here, we present the first report on bone morphology, bone density and bone microstructure in two adult MOPD1 patients and applied radiographs, dual energy X-ray absorptiometry, high-resolution peripheral quantitative computed tomography and biochemical evaluation. The MOPD1 patients presented with short stature, low BMI but normal macroscopic bone configuration. Bone mineral density was low. Compared to Danish reference data, total bone area, cortical bone area, cortical thickness, total bone density, cortical bone density, trabecular bone density and trabecular bone volume per tissue volume (BV/TV) were all low. These findings may correlate to the short stature and low body weight of the MOPD1 patients. Our findings suggest that minor spliceosome malfunction may be associated with altered bone modelling. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Volumetric laser endomicroscopy in the biliary and pancreatic ducts: a feasibility study with histological correlation.

PubMed

Corral, Juan E; Mousa, Omar Y; Krishna, Murli; Levink, Iris J M; Pursell, Khela R; Afsh, Mohammad; Kröner, Paul T; Harnois, Denise M; Wolfsen, Herbert C; Wallace, Michael B; Lukens, Frank J

2018-06-18

 Volumetric laser endomicroscopy (VLE) provides circumferential images 3 mm into the biliary and pancreatic ducts. We aimed to correlate VLE images with the normal and abnormal microstructure of these ducts. Samples from patients undergoing hepatic or pancreatic resection were evaluated. VLE images were collected using a low-profile VLE catheter inserted manually into the biliary and pancreatic ducts ex vivo. Histological correlation was assessed by two unblinded investigators.  25 patients (20 liver and 5 pancreatic samples) and 111 images were analyzed. VLE revealed three histological layers: epithelium, connective tissue, and parenchyma. It identified distinctive patterns for primary sclerosing cholangitis (PSC), pancreatic cysts, neuroendocrine tumor, and adenocarcinoma adjacent to the pancreatic duct or ampulla. VLE failed to identify dysplasia in a dominant stricture and inflammatory infiltrates in PSC. Reflectivity measurements of the liver parenchyma diagnosed liver cirrhosis with high sensitivity.  VLE can identify histological changes in the biliary and pancreatic ducts allowing real-time diagnosis. Further studies are needed to measure the accuracy of VLE in a larger sample and to validate our findings in vivo. © Georg Thieme Verlag KG Stuttgart · New York.

Three different methods for treating multiple enchondromatosis in one hand.

PubMed

Lu, Hui; Chen, Qiang; Shen, Hui; Shen, Xiang-Qian; Wu, Shou-Cheng; Lin, Xiang-Jin

2015-01-01

Ollier's disease remains comparatively rare, and is a non-hereditary cartilage dysplasia of bone. It is usually associated with problems such as deformity and fracture. Three different methods were used in a one-hand of 15-year-old boy reporting his pain in the left hand and swellings. After the curettage of tumor, regarding as the differences of all parts of the bone structure reconstruction in the patient's hand, we chose three following methods for this boy, i.e. fixed by the locking plate with calcium phosphate cement, filled with allograft bone, curetted the tumor without any bone graft. After the surgery, the patient was able to perform full motion of the operated hand. No evidence of recurrence was noted four years after surgery. To choose the different ways with bone grafts or not that relies on the patients' conditions for bone structure reconstruction. However, patients with large osseous defects or pathological fracture, we demand full bone graft and reliable internal fixation. After surgery, early exercises can reach a desirable result and functional recovery.

Bone marrow morphology and disease progression in congenital thrombocytopenia: a detailed clinicopathologic and genetic study of eight cases.

PubMed

Tsang, Hamilton C; Bussel, James B; Mathew, Susan; Liu, Yen-Chun; Imahiyerobo, Allison A; Orazi, Attilio; Geyer, Julia T

2017-04-01

Patients with congenital thrombocytopenia have an increased risk of developing myeloid neoplasms. In these cases, the morphologic distinction between disease at baseline and at progression is challenging. This report analyzes clinicopathologic features of congenital thrombocytopenia with long-term follow-up at one referral center. Records from the last 20 years were searched for cases of congenital thrombocytopenia with bone marrow biopsies and peripheral blood smears. The clinical, morphologic, immunophenotypic, and molecular features were analyzed. Six adult and two pediatric patients were identified (six male, two female). Age range at first biopsy was 1-47 (median, 31) years. Underlying diseases included thrombocytopenia-absent radius syndrome, congenital thrombocytopenia with radial-ulnar synostosis, MYH9-related disorder, shortened telomere syndrome, congenital thrombocytopenia with ANKRD26 mutation, and familial platelet disorder with predisposition to acute myeloid leukemia. Four patients had myelodysplastic/myeloproliferative neoplasm-like marrow changes such as hypercellularity, increased myeloid to erythroid ratio, numerous micromegakaryocytes (highlighted by CD42b), and marrow fibrosis. Two patients had marrow hypoplasia and two had unremarkable marrow morphology. Three patients-all in the myelodysplastic/myeloproliferative neoplasm-like group-developed disease progression characterized by erythroid and myeloid dysplasia, elevated bone marrow blasts, and new cytogenetic abnormalities. Unlike non-familial myeloid neoplasms, congenital thrombocytopenia patients in the myelodysplastic/myeloproliferative neoplasm-like group had a long and indolent clinical course (average age at disease progression, 47 years). In summary, three distinct morphologic types of congenital thrombocytopenia were identified: a hyperplastic myelodysplastic/myeloproliferative neoplasm-like group, a hypoplastic bone marrow failure-like group, and a group with relatively normal marrow morphology. Emergence of cytogenetic abnormalities and dysplasia in non-megakaryocyte lineages correlated with disease progression.

Intraductal location of the sclerosing adenosis of the breast.

PubMed

Unal, Bulent; Gur, A Serhat; Bhargava, Rohit; Edington, Howard; Ahrendt, Gretchen; Soran, Atilla

2009-01-01

Sclerosing adenosis is a benign breast disease with non-specific images on ultrasound or mammogram. It can mimic infiltrating carcinoma when the above mentioned imaging techniques are used. Herein we present a patient with breast cancer who received neoadjuvant chemotherapy and subsequently underwent mastectomy. Ductoscopy was performed to the mastectomised breast specimen as per the ductoscopy research protocol. Ductoscopy revealed several nodular lesions in the duct with no additional demonstrable intraductal pathology. The lesions were reported as sclerosing adenosis by pathologist. As to our knowledge, this is the first case in literature that demonstrates the use of ductoscopy in diagnosing the sclerosing adenosis in the breast tissue. Ductoscopy and development of ductoscopy guided biopsy techniques may be used as an early diagnostic method for the ductal breast lesions (Fig. 2, Ref. 10). Full Text (Free, PDF) www.bmj.sk.

IgG4-negative autoimmune pancreatitis with sclerosing cholangitis and colitis: possible association with primary sclerosing cholangitis?

PubMed

Saeki, Keita; Hozawa, Shigenari; Miyata, Naoteru; Nishizawa, Toshihiro; Soma, Hiromitsu; Iwao, Yasushi; Kameyama, Kaori; Hibi, Toshifumi

2008-01-01

We report a case of autoimmune pancreatitis (AIP) with cholangiography and histopathology showing features characteristic of primary sclerosing cholangitis (PSC) and colitis. A 55-year-old previously-healthy man was diagnosed with anti-nuclear antibody (ANA)-positive AIP according to the finding of serum biochemistry, abdominal US (ultrasonography), CT (computed tomography) and ERCP (endoscopic retrograde cholangiopancreatography). However, bead-like strictures of intrahepatic bile ducts were also found and liver tissue showed onion skin-like periductal fibrosis but no anti-IgG4-positive cells. In addition, colon fiberscopy showed a pancolitis similar to ulcerative colitis indicating that, in this case, there may be an association with PSC. Here, we report a rare case of IgG4-negative AIP with sclerosing cholangitis and colitis with many clinical features that support an association with PSC.

Morphological changes in vascular and circulating blood cells following exposure to detergent sclerosants.

PubMed

Cooley-Andrade, O; Connor, D E; Ma, D D F; Weisel, J W; Parsi, K

2016-04-01

To investigate morphological changes in vascular and circulating blood cells following exposure to detergent sclerosants sodium tetradecyl sulfate and polidocanol. Samples of whole blood, isolated leukocytes, platelets, endothelial cells, and fibroblasts were incubated with varying concentrations of sclerosants. Whole blood smears were stained with Giemsa and examined by light and bright field microscopy. Phalloidin and Hoechst stains were used to analyze cytoplasmic and nuclear morphology by fluorescence microscopy. Endothelial cell and fibroblasts were analyzed by live cell imaging. Higher concentrations of sclerosants induced cell lysis. Morphological changes in intact cells were observed at sublytic concentrations of detergents. Low concentration sodium tetradecyl sulfate induced erythrocyte acanthocytosis and macrocytosis, while polidocanol induced Rouleaux formation and increased the population of target cells and stomatocytes. Leukocytes showed swelling, blebbing, vacuolation, and nuclear degradation following exposure to sodium tetradecyl sulfate, while polidocanol induced pseudopodia formation, chromatin condensation, and fragmentation. Platelets exhibited pseudopodia with sodium tetradecyl sulfate and a "fried egg" appearance with polidocanol. Exposure to sodium tetradecyl sulfate resulted in size shrinkage in both endothelial cell and fibroblasts, while endothelial cell developed distinct spindle morphology. Polidocanol induced cytoplasmic microfilament bundles in both endothelial cell and fibroblasts. Patchy chromatin condensation was observed following exposure of fibroblasts to either agent. Detergent sclerosants are biologically active at sublytic concentrations. The observed morphological changes are consistent with cell activation, apoptosis, and oncosis. The cellular response is concentration dependent, cell-specific, and sclerosant specific. © The Author(s) 2015.

Whole-genome sequencing of Atacama skeleton shows novel mutations linked with dysplasia

PubMed Central

Bhattacharya, Sanchita; Li, Jian; Sockell, Alexandra; Kan, Matthew J.; Bava, Felice A.; Chen, Shann-Ching; Ávila-Arcos, María C.; Ji, Xuhuai; Smith, Emery; Asadi, Narges B.; Lachman, Ralph S.; Lam, Hugo Y.K.; Bustamante, Carlos D.; Butte, Atul J.; Nolan, Garry P.

2018-01-01

Over a decade ago, the Atacama humanoid skeleton (Ata) was discovered in the Atacama region of Chile. The Ata specimen carried a strange phenotype—6-in stature, fewer than expected ribs, elongated cranium, and accelerated bone age—leading to speculation that this was a preserved nonhuman primate, human fetus harboring genetic mutations, or even an extraterrestrial. We previously reported that it was human by DNA analysis with an estimated bone age of about 6–8 yr at the time of demise. To determine the possible genetic drivers of the observed morphology, DNA from the specimen was subjected to whole-genome sequencing using the Illumina HiSeq platform with an average 11.5× coverage of 101-bp, paired-end reads. In total, 3,356,569 single nucleotide variations (SNVs) were found as compared to the human reference genome, 518,365 insertions and deletions (indels), and 1047 structural variations (SVs) were detected. Here, we present the detailed whole-genome analysis showing that Ata is a female of human origin, likely of Chilean descent, and its genome harbors mutations in genes (COL1A1, COL2A1, KMT2D, FLNB, ATR, TRIP11, PCNT) previously linked with diseases of small stature, rib anomalies, cranial malformations, premature joint fusion, and osteochondrodysplasia (also known as skeletal dysplasia). Together, these findings provide a molecular characterization of Ata's peculiar phenotype, which likely results from multiple known and novel putative gene mutations affecting bone development and ossification. PMID:29567674

Achondroplasia: Development, Pathogenesis, and Therapy

PubMed Central

Ornitz, David M.; Legeai-Mallet, Laurence

2016-01-01

Autosomal dominant mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) cause Achondroplasia (Ach), the most common form of dwarfism in humans, and related chondrodysplasia syndromes that include Hypochondroplasia (Hch), Severe Achondroplasia with Developmental Delay and Acanthosis Nigricans (SADDAN), and Thanatophoric dysplasia (TD). FGFR3 is expressed in chondrocytes and mature osteoblasts where it functions to regulate bone growth. Analysis of the mutations in FGFR3 revealed increased signaling through a combination of mechanisms that include stabilization of the receptor, enhanced dimerization, and enhanced tyrosine kinase activity. Paradoxically, increased FGFR3 signaling profoundly suppresses proliferation and maturation of growth plate chondrocytes resulting in decreased growth plate size, reduced trabecular bone volume, and resulting decreased bone elongation. In this review we discuss the molecular mechanisms that regulate growth plate chondrocytes, the pathogenesis of Ach, and therapeutic approaches that are being evaluated to improve endochondral bone growth in people with Ach and related conditions. PMID:27987249

Melorheostosis of the ulna.

PubMed

Abdullah, Shalimar; Pang, Gerry M H; Mohamed-Haflah, Nor Hazla; Sapuan, Jamari

2011-10-01

Melorheostosis is a rare osteosclerotic bone dysplasia. It is usually characterized by dull and aching pain, reduced joint motion and contractures. Classic radiograph findings are of undulating cortical hyperostosis along the length of the bone, simulating a "dripping candlewax appearance". We report two cases of melorheostosis of the ulna bone, diagnosed 6 years apart in two different females in their early 20s. Both the patients presented with the characteristic features of dull and aching pain in the forearm and were treated conservatively. However, we misdiagnosed the first case as bone malignancy and subjected the patient to a biopsy. For the second case, with hindsight we made the correct diagnosis based only on the classic clinical history and radiographs. We believe that the discussion of a misdiagnosed case of melorheostosis with salient findings may be important for clinicians and orthopedicians in day-to-day clinical practice. Copyright © 2011. Published by Elsevier B.V.

MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta

PubMed Central

Lindert, Uschi; Cabral, Wayne A.; Ausavarat, Surasawadee; Tongkobpetch, Siraprapa; Ludin, Katja; Barnes, Aileen M.; Yeetong, Patra; Weis, Maryann; Krabichler, Birgit; Srichomthong, Chalurmpon; Makareeva, Elena N.; Janecke, Andreas R.; Leikin, Sergey; Röthlisberger, Benno; Rohrbach, Marianne; Kennerknecht, Ingo; Eyre, David R.; Suphapeetiporn, Kanya; Giunta, Cecilia; Marini, Joan C.; Shotelersuk, Vorasuk

2016-01-01

Osteogenesis imperfecta (OI) is a collagen-related bone dysplasia. We identified an X-linked recessive form of OI caused by defects in MBTPS2, which encodes site-2 metalloprotease (S2P). MBTPS2 missense mutations in two independent kindreds with moderate/severe OI cause substitutions at highly conserved S2P residues. Mutant S2P has normal stability, but impaired functioning in regulated intramembrane proteolysis (RIP) of OASIS, ATF6 and SREBP transcription factors, consistent with decreased proband secretion of type I collagen. Further, hydroxylation of the collagen lysine residue (K87) critical for crosslinking is reduced in proband bone tissue, consistent with decreased lysyl hydroxylase 1 in proband osteoblasts. Reduced collagen crosslinks presumptively undermine bone strength. Also, proband osteoblasts have broadly defective differentiation. These mutations provide evidence that RIP plays a fundamental role in normal bone development. PMID:27380894

Exome sequencing reveals two novel compound heterozygous XYLT1 mutations in a Polish patient with Desbuquois dysplasia type 2 and growth hormone deficiency.

PubMed

Jamsheer, Aleksander; Olech, Ewelina M; Kozłowski, Kazimierz; Niedziela, Marek; Sowińska-Seidler, Anna; Obara-Moszyńska, Monika; Latos-Bieleńska, Anna; Karczewski, Marek; Zemojtel, Tomasz

2016-07-01

Desbuquois dysplasia type 2 (DBQD2) is a rare recessively inherited skeletal genetic disorder characterized by severe prenatal and postnatal growth retardation, generalized joint laxity with dislocation of large joints and facial dysmorphism. The condition was recently described to result from autosomal recessive mutations in XYLT1, encoding the enzyme xylosyltransferase-1. In this paper, we report on a Polish patient with DBQD2 who presented with severe short stature of prenatal onset, joint laxity, psychomotor retardation and multiple radiological abnormalities including short metacarpals, advanced bone age and exaggerated trochanters. Endocrinological examinations revealed that sleep-induced growth hormone (GH) release and GH peak in clonidine- and glucagon-induced provocative tests as well as insulin-like growth factor 1 (IGF-1) and IGF-binding protein-3 levels were all markedly decreased, confirming deficiency of GH secretion. Bone age, unlikely to GH deficiency, was significantly advanced. To establish the diagnosis at a molecular level, we performed whole-exome sequencing and bioinformatic analysis in the index patient, which revealed compound heterozygous XYLT1 mutations: c.595C>T(p.Gln199*) and c.1651C>T(p.Arg551Cys), both of which are novel. Sanger sequencing showed that the former mutation was inherited from the healthy mother, whereas the latter one most probably occurred de novo. Our study describes the first case of DBQD2 resulting from compound heterozygous XYLT1 mutation, expands the mutational spectrum of the disease and provides evidence that the severe growth retardation and microsomia observed in DBQD2 patients may result not only from the skeletal dysplasia itself but also from GH and IGF-1 deficiency.

ALTA injection sclerosing therapy:non-excisional treatment of internal hemorrhoids.

PubMed

Miyamoto, Hidenori; Asanoma, Michihito; Miyamoto, Hideyuki; Shimada, Mitsuo

2012-01-01

Aluminum potassium sulfate and tannic acid (ALTA) is a new sclerosing therapy for internal hemorrhoids. This injection therapy is a four-step direct injection sclerosing procedure intended to shrink and harden internal hemorrhoids to eliminate hemorrhoidal prolapse and bleeding. The aim of this study was to assess the short term efficacy of this treatment. The procedure was conducted using a four-step injection process under perianal local anesthesia. The entry point for the four-step injection of ALTA is the submucosa of the superior pole, the submucosa in the central part, the mucous lamina propria in the central part and the submucosa at the inferior pole of hemorrhoid. From January 2009 to March 2010, we performed the ALTA sclerosing therapy on 28 patients (14 men and 14 women; mean age, 64.6 years), including 5 second-degree, 16 third-degree and 7 fourth-degree hemorrhoids. There were 6 postoperative complications (2 cases of low grade fever, 2 anal pains, 1 necrosis at injection site and 1 perianal dermatitis). All symptoms of prolapse or bleeding disappeared after 29 postoperative days. There were 3 recurrent cases (10.7%). ALTA sclerosing therapy is a useful and less invasive treatment for internal hemorrhoids.

Diffuse sclerosing variant of thyroid carcinoma presenting as Hashimoto thyroiditis: a case report.

PubMed

Vukasović, Anamarija; Kuna, Sanja Kusacić; Ostović, Karmen Trutin; Prgomet, Drago; Banek, Tomislav

2012-11-01

The aim of report is to present a case of a rare diffuse sclerosing variant of a papillary thyroid carcinoma. A 15-year old girl referred for ultrasound examination because of painless thyroid swelling lasting 10 days before. An ultrasound of the neck showed diffusely changed thyroid parenchyma, without nodes, looking as lymphocytic thyroiditis Hashimoto at first, but with snow-storm appearance, predominantly in the right lobe. Positive thyroid peroxidase antibodies (TPO-AT) also suggested Hashimoto thyroiditis. Repeated US-FNAB (fine needle-aspiration biopsy) of the right lobe revealed diffuse sclerosing variant of papillary thyroid carcinoma and patient underwent total thyreoidectomy. Patohistologic finding confirmed diffuse sclerosing variant of a papillary thyroid carcinoma in the both thyroid lobes and several metastatic lymph nodes. Two months later patient recived radioablative therapy with 3700 MBq (100 mCi) of 1-131 followed by levothyroxine replacement. At the moment, patient is without evidence of local or distant metastases and next regular control is scheduled in 6 months. In conclusion, a diffuse sclerosing variant is rare form of papillary thyroid carcinoma that echographically looks similar to Hashimoto thyroiditis and sometimes could be easily overlooked.

Epilepsia partialis continua in children with fulminant subacute sclerosing panencephalitis.

PubMed

Kravljanac, Ruzica; Jovic, Nebojsa; Djuric, Milena; Nikolic, Ljubica

2011-12-01

Various inflammatory diseases of central nervous system, including subacute sclerosing panencephalitis, could cause epilepsia partialis continua. Two boys with epilepsia partialis continua with onset in terminal phase of atypical subacute sclerosing panencephalitis have been reported. Children were not vaccinated against measles, and the second case had history of measles at an early age. In both cases, the onset of subacute sclerosing panencephalitis was characterized by altered behavior and cognitive decline with very fast mental and neurological deterioration. One boy was suffering from complex partial seizures and myoclonic jerks synchronous with periodic electroencephalographic pattern. Diagnosis was proved by increased titers of antimeasles antibodies in both serum and cerebrospinal fluid. In terminal phase of the disease, epilepsia partialis continua of localized group of the muscles was diagnosed, with good response to intravenous infusion of midazolam. Surface electroencephalographic recordings during epilepsia partialis continua did not show the epileptic discharges. During the terminal phase of the disease, no other type of seizures and movement disorders were recognized, except epilepsia partialis continua. In spite of the treatment, period from the onset of disease to death lasted less than 3 months, suggesting very fulminant course of subacute sclerosing panencephalitis.

Facial clefts and facial dysplasia: revisiting the classification.

PubMed

Mazzola, Riccardo F; Mazzola, Isabella C

2014-01-01

Most craniofacial malformations are identified by their appearance. The majority of the classification systems are mainly clinical or anatomical, not related to the different levels of development of the malformation, and underlying pathology is usually not taken into consideration. In 1976, Tessier first emphasized the relationship between soft tissues and the underlying bone stating that "a fissure of the soft tissue corresponds, as a general rule, with a cleft of the bony structure". He introduced a cleft numbering system around the orbit from 0 to 14 depending on its relationship to the zero line (ie, the vertical midline cleft of the face). The classification, easy to understand, became widely accepted because the recording of the malformations was simple and communication between observers facilitated. It represented a great breakthrough in identifying craniofacial malformations, named clefts by him. In the present paper, the embryological-based classification of craniofacial malformations, proposed in 1983 and in 1990 by us, has been revisited. Its aim was to clarify some unanswered questions regarding apparently atypical or bizarre anomalies and to establish as much as possible the moment when this event occurred. In our opinion, this classification system may well integrate the one proposed by Tessier and tries at the same time to find a correlation between clinical observation and morphogenesis.Terminology is important. The overused term cleft should be reserved to true clefts only, developed from disturbances in the union of the embryonic facial processes, between the lateronasal and maxillary process (or oro-naso-ocular cleft); between the medionasal and maxillary process (or cleft of the lip); between the maxillary processes (or cleft of the palate); and between the maxillary and mandibular process (or macrostomia).For the other types of defects, derived from alteration of bone production centers, the word dysplasia should be used instead. Facial dysplasias have been ranged in a helix form and named after the site of the developmental arrest. Thus, an internasal, nasal, nasomaxillary, maxillary and malar dysplasia, depending on the involved area, have been identified.The classification may provide a useful guide in better understanding the morphogenesis of rare craniofacial malformations.

Association of mutations with morphological dysplasia in de novo acute myeloid leukemia without 2016 WHO Classification-defined cytogenetic abnormalities

PubMed Central

Weinberg, Olga K.; Gibson, Christopher J.; Blonquist, Traci M.; Neuberg, Donna; Pozdnyakova, Olga; Kuo, Frank; Ebert, Benjamin L.; Hasserjian, Robert P.

2018-01-01

Despite improvements in our understanding of the molecular basis of acute myeloid leukemia (AML), the association between genetic mutations with morphological dysplasia remains unclear. In this study, we evaluated and scored dysplasia in bone marrow (BM) specimens from 168 patients with de novo AML; none of these patients had cytogenetic abnormalities according to the 2016 World Health Organization Classification. We then performed targeted sequencing of diagnostic BM aspirates for recurrent mutations associated with myeloid malignancies. We found that cohesin pathway mutations [q (FDR-adjusted P)=0.046] were associated with a higher degree of megakaryocytic dysplasia and STAG2 mutations were marginally associated with greater myeloid lineage dysplasia (q=0.052). Frequent megakaryocytes with separated nuclear lobes were more commonly seen among cases with cohesin pathway mutations (q=0.010) and specifically in those with STAG2 mutations (q=0.010), as well as NPM1 mutations (q=0.022 when considering the presence of any vs. no megakaryocytes with separated nuclear lobes). RAS pathway mutations (q=0.006) and FLT3-ITD (q=0.006) were significantly more frequent in cases without evaluable erythroid cells. In univariate analysis of the 153 patients treated with induction chemotherapy, NPM1 mutations were associated with longer event-free survival (EFS) (P=0.042), while RUNX1 (P=0.042), NF1 (P=0.040), frequent micromegakaryocytes (P=0.018) and presence of a subclone (P=0.002) were associated with shorter EFS. In multivariable modeling, NPM1 was associated with longer EFS, while presence of a subclone and frequent micromegakaryocytes remained significantly associated with shorter EFS. PMID:29326119

Secondary sclerosing cholangitis in critically ill patients.

PubMed

Peña-Pérez, Carlos Alberto; Ponce-Medrano, Juan Alberto Díaz

2018-01-01

Primary sclerosing cholangitis (PSC) is a rare idiopathic condition with immunopathogenic mechanisms where there is chronic progressive destruction of the biliary tree. Secondary sclerosing cholangitis (SSC) is clinically comparable to PSC, but is caused by specific processes which directly damage the biliary tree; examples include recurrent pancreatitis, bile duct malignancy, congenital bile duct abnormalities. A new cause of SSC has been described during or following significant critical illness associated with severe respiratory insufficiency, vasopressor requirement, shock and sepsis. This condition rapidly progresses to cirrhosis, frequently requiring liver transplantation for definitive management. Copyright: © 2018 Permanyer.

Rapidly progressive subacute sclerosing panencephalitis presenting with acute loss of vision.

PubMed

Ekici, Bariş; Calişkan, Mine; Tatli, Burak; Aydinli, Nur; Ozmen, Meral

2011-12-01

A 10-year-old male presented with vision loss and behavioral changes. He had midpoint pupils with no reaction to light and normal funduscopic examination. Cranial magnetic resonance imaging revealed bilateral cortical lesions at parieto-occipital lobes. Elevated measles antibody titers in the cerebrospinal fluid confirmed the diagnosis of subacute sclerosing panencephalitis. Despite oral inosiplex and supportive care, patient developed generalized seizures with frequent myoclonic jerks and rapidly progressed into coma. Cortical blindness in subacute sclerosing panencephalitis can be an early indicator for fulminant course.

Pathological fractures in children

PubMed Central

De Mattos, C. B. R.; Binitie, O.; Dormans, J. P.

2012-01-01

Pathological fractures in children can occur as a result of a variety of conditions, ranging from metabolic diseases and infection to tumours. Fractures through benign and malignant bone tumours should be recognised and managed appropriately by the treating orthopaedic surgeon. The most common benign bone tumours that cause pathological fractures in children are unicameral bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. Although pathological fractures through a primary bone malignancy are rare, these should be recognised quickly in order to achieve better outcomes. A thorough history, physical examination and review of plain radiographs are crucial to determine the cause and guide treatment. In most benign cases the fracture will heal and the lesion can be addressed at the time of the fracture, or after the fracture is healed. A step-wise and multidisciplinary approach is necessary in caring for paediatric patients with malignancies. Pathological fractures do not have to be treated by amputation; these fractures can heal and limb salvage can be performed when indicated. PMID:23610658

[Computed tomography of the temporal bone in diagnosis of chronic exudative otitis media].

PubMed

Zelikovich, E I

2005-01-01

Computed tomography (CT) of the temporal bone was made in 37 patients aged 2 to 55 years with chronic exudative otitis media (CEOM). In 21 of them the pathology was bilateral. The analysis of 58 CT images has identified CT signs of chronic exudative otitis media. They include partial (17 temporary bones) or complete (38 temporal bones) block of the bone opening of the auditory tube, pneumatic defects of the tympanic cavity (58 temporal bones), pneumatic defects of the mastoid process and antrum (47 temporal bones), pathologic retraction of the tympanic membrane. The examination of the temporal bone detected both CT-signs of CEOM and other causes of hearing disorders in 14 patients (26 temporal bones) with CEOM symptoms and inadequately high hypoacusis. Among these causes were malformation of the auditory ossicula (n=5), malformation of the labynthine window (n=2), malformation of the middle and internal ear (n=4), a wide aqueduct of the vestibule, labyrinthine anomaly of Mondini's type (n=1), cochlear hypoplasia (n=4), stenosis of the internal acoustic meatuses (n=2). Sclerotic fibrous dysplasia was suggested in 2 temporal bones (by CT data). CT was repeated after surgical treatment of 10 patients (14 temporal bones) and visual assessment of tympanostomy results was made.

Subacute sclerosing panencephalitis in pregnancy.

PubMed

Chiu, Michael H; Meatherall, Bonnie; Nikolic, Ana; Cannon, Kristine; Fonseca, Kevin; Joseph, Jeffrey T; MacDonald, Judy; Pabbaraju, Kanti; Tellier, Raymond; Wong, Sallene; Koch, Marcus W

2016-03-01

We present a case of subacute sclerosing panencephalitis that developed in a previously healthy 29-year-old pregnant woman who had returned from a trip to rural India shortly before the onset of symptoms. She was admitted to hospital at 27 weeks' gestation with a history of cognitive decline and difficulty completing simple tasks. She had no clinical signs of infection. The working diagnosis was autoimmune encephalitis, although extensive investigations did not lead to a final classifying diagnosis. The patient became comatose and developed hypertension, and an emergency caesarean section was done at 31 weeks to deliver the child, who seemed healthy. The patient died about 6 weeks after the onset of symptoms. The patient was found to have had subacute sclerosing panencephalitis at autopsy. In this Grand Round, we review the clinical features and treatment of subacute sclerosing panencephalitis, and the epidemiological and public health aspects of the case. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cytogenetic study of a pulmonary sclerosing hemangioma.

PubMed

Pareja, María J; Vargas, María T; Sánchez, Ana; Ibáñez, José; González-Cámpora, Ricardo

2009-11-01

Pulmonary sclerosing hemangioma (PSH) is an uncommon benign tumor that presents as a solitary asymptomatic and slow-growing nodule. It occurs in both young and old persons; peak incidence is in the fifth decade. Both sexes are affected by this tumor, but women more frequently than men. On histological examination, PSH shows prominent sclerotization and vascularization of the tissue. Recent studies conclude that PSH derives from type II pneumocytes, but the potential for progression and histogenesis remains controversial. We report a case of pulmonary sclerosing hemangioma in a 61-year-old woman with a neoplastic node 1 cm in diameter. The karyotype was 46,XX,t(8;18),der(14;15),+14 in all the cells analyzed. PTEN (10q23) and IgH (14q32) probes were analyzed in interphase nuclei and paraffin-embedded tissues of tumor cells. These chromosome abnormalities could provide information about the relationship of genetic changes to the biological properties of sclerosing hemangioma tumors.

Juvenile psammomatoid ossifying fibroma of the neurocranium. Report of four cases.

PubMed

Hasselblatt, Martin; Jundt, Gernot; Greiner, Christoph; Rama, Burckhard; Schmäl, Frank; Iglesias-Rozas, José R; van de Nes, Johannes A P; Paulus, Werner

2005-06-01

Juvenile psammomatoid ossifying fibroma (JPOF) is a benign fibroosseous lesion predominantly arising within the paranasal sinuses in children and young adults. Neurocranial occurrence is exceedingly rare and a location within the neurocranial portion of the temporal bone has not been described. The authors report on one case of sinonasal JPOF secondarily extending into the cranial cavity and three cases primarily affecting the neurocranial bones to increase clinical awareness of this uncommon tumor, which may be easily mistaken for meningioma. Moreover, the absence of activating missense mutations of the GNAS1 gene in two cases strongly argues against a relationship between JPOF and fibrous dysplasia.

Brain and Bone Damage in KARAP/DAP12 Loss-of-Function Mice Correlate with Alterations in Microglia and Osteoclast Lineages

PubMed Central

Nataf, Serge; Anginot, Adrienne; Vuaillat, Carine; Malaval, Luc; Fodil, Nassima; Chereul¶, Emmanuel; Langlois¶, Jean-Baptiste; Dumontel, Christiane; Cavillon, Gaelle; Confavreux, Christian; Mazzorana, Marlène; Vico, Laurence; Belin, Marie-Franaçoise; Vivier, Eric; Tomasello, Elena; Jurdic, Pierre

2005-01-01

Human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy, also known as Nasu-Hakola disease, has been described to be associated with mutations affecting the immunoreceptor tyrosine-based activation motif-bearing KARAP/DAP12 immunoreceptor gene. Patients present bone fragilities and severe neurological alterations leading to presenile dementia. Here we investigated whether the absence of KARAP/DAP12-mediated signals in loss-of-function (KΔ75) mice also leads to bone and central nervous system pathological features. Histological analysis of adult KΔ75 mice brains revealed a diffuse hypomyelination predominating in anterior brain regions. As this was not accompanied by oligodendrocyte degeneration or microglial cell activation it suggests a developmental defect of myelin formation. Interestingly, in postnatal KΔ75 mice, we observed a dramatic reduction in microglial cell numbers similar to in vitro microglial cell differentiation impairment. Our results raise the intriguing possibility that defective microglial cell differentiation might be responsible for abnormal myelin development. Histomorphometry revealed that bone remodeling is also altered, because of a resorption defect, associated with a severe block of in vitro osteoclast differentiation. In addition, we show that, among monocytic lineages, KARAP/DAP12 specifically controls microglial and osteoclast differentiation. Our results confirm that KARAP/DAP12-mediated signals play an important role in the regulation of both brain and bone homeostasis. Yet, important differences exist between the symptoms observed in Nasu-Hakola patients and KΔ75 mice. PMID:15632019

Expanded clinical spectrum of spondylocarpotarsal synostosis syndrome and possible manifestation in a heterozygous father.

PubMed

Mitter, Diana; Krakow, Deborah; Farrington-Rock, Claire; Meinecke, Peter

2008-03-15

We report on a 5-year-old boy with spondylocarpotarsal synostosis (SCT) syndrome who presents with disproportionate short stature, thoracic scoliosis, pes planus, dental enamel hypoplasia, unilateral conductive hearing loss and mild facial dysmorphisms. Radiographs showed abnormal segmentation of the spine with block vertebrae and carpal synostosis. In addition to the typical phenotype of SCT syndrome, he showed pronounced delay of carpal bone age and bilateral epiphyseal dysplasia of the proximal femora. The patient's father has mild short stature and unilateral hip dysplasia. Molecular studies of the filamin B gene (FLNB) revealed a homozygous mutation in the index patient while both parents were heterozygous for the mutation. In this report we expand the phenotype of SCT syndrome in a patient with a causal FLNB mutation. (c) 2008 Wiley-Liss, Inc.

Complete occipitalization of the atlas with bilateral external auditory canal atresia.

PubMed

Dolenšek, Janez; Cvetko, Erika; Snoj, Žiga; Meznaric, Marija

2017-09-01

Fusion of the atlas with the occipital bone is a rare congenital dysplasia known as occipitalization of the atlas, occipitocervical synostosis, assimilation of the atlas, or atlanto-occipital fusion. It is a component of the paraxial mesodermal maldevelopment and commonly associated with other dysplasias of the craniovertebral junction. External auditory canal atresia or external aural atresia is a rare congenital absence of the external auditory canal. It occurs as the consequence of the maldevelopment of the first pharyngeal cleft due to defects of cranial neural crest cells migration and/or differentiation. It is commonly associated with the dysplasias of the structures derived from the first and second pharyngeal arches including microtia. We present the coexistence of the occipitalization of the atlas and congenital aural atresia, an uncommon combination of the paraxial mesodermal maldevelopment, and defects of cranial neural crest cells. The association is most probably syndromic as minimal diagnostic criteria for the oculoariculovertebral spectrum are fulfilled. From the clinical point of view, it is important to be aware that patients with microtia must obtain also appropriate diagnostic imaging studies of the craniovetebral junction due to eventual concomitant occipitalization of the atlas and frequently associated C1-C2 instability.

Current therapies and future perspectives in subacute sclerosing panencephalitis.

PubMed

Tatli, Burak; Ekici, Bariş; Ozmen, Meral

2012-04-01

Subacute sclerosing panencephalitis is a progressive neurological disorder of children and young adults caused by a measles virus that became defective by persisting in the host. According to the results of clinical trials, antiviral and/or immunomodulatory therapy can slow the progression of the disease and improve life expectancy in patients. However, its long-term effects and eventual outcome remain debatable due to conflicting results and its lack of effect on the rapidly progressive form of the disease. Possible future therapies for subacute sclerosing panencephalitis are RNAi and antiapoptotic agents, which are currently in the hypothetical and experimental stages of research.

[Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: description of a case].

PubMed

Cavazza, A; Toschi, E; Valcavi, R; Piana, S; Scotti, R; Carlinfante, G; Gardini, G

1999-02-01

A case of sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid gland is described. The patient, a 32 year-old female with Hashimoto's thyroiditis, presented with a 4 cm nodule of the right lobe of the thyroid gland. The tumour was constituted by squamoid cords infiltrating a dense fibro-jaline stroma rich in eosinophils. The patient is alive and well 14 months after surgery. The literature is briefly reviewed and the differential diagnosis is discussed. In the Author's opinion, sclerosing mucoepidermoid carcinoma with eosinophilia of the tyroid is a well defined clinicopathological entity.

Subacute sclerosing panencephalitis (SSPE): an insight into the diagnostic errors from a tertiary care university hospital.

PubMed

Prashanth, L K; Taly, A B; Sinha, S; Ravi, V

2007-06-01

Subacute sclerosing panencephalitis (SSPE) is a progressive disease caused by wild-type measles virus leading to premature death. Early diagnosis may help in medical interventions and counseling. The aim of this study was to ascertain diagnostic errors and their possible causes. Retrospective case record analysis of patients with subacute sclerosing panencephalitis, evaluated over a 10-year period, was performed. The following data were analyzed: initial symptoms and diagnosis, interval between onset of symptoms to diagnosis, and implications of delayed diagnosis. Among the 307 patients evaluated, initial diagnosis by various health care professionals was other than subacute sclerosing panencephalitis in 242 patients (78.8%). These included seizures, absence seizures, metachromatic leukodystrophy, Schilder's disease, cerebral palsy, hemiparkinsonism, Wilson's disease, vasculitis, spinocerebellar ataxia, motor neuron disease, nutritional amblyopia, tapetoretinal degeneration, catatonic schizophrenia, and malingering, among others. The interval between precise diagnosis and first reported symptom was 6.2 +/- 11.3 months (range, 0.2-96 months; median, 3 months). Forty-four patients (14.3%) who had symptoms for more than 1 year before the precise diagnosis had a protracted course as compared to the rest of the cohort ( P = .0001). Early and accurate diagnosis of subacute sclerosing panencephalitis needs a high index of suspicion.

Current therapies for Morquio A syndrome and their clinical outcomes

PubMed Central

Sawamoto, Kazuki; Suzuki, Yasuyuki; Mackenzie, William G.; Theroux, Mary C.; Pizarro, Christian; Yabe, Hiromasa; Orii, Kenji E.; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

2016-01-01

Introduction Morquio A syndrome is characterized by a unique skeletal dysplasia, leading to short neck and trunk, pectus carinatum, laxity of joints, kyphoscoliosis, and tracheal obstruction. Cervical spinal cord compression/inability, a restrictive and obstructive airway, and/or bone deformity and imbalance of growth, are life-threatening to Morquio A patients, leading to a high morbidity and mortality. It is critical to review the current therapeutic approaches with respect to their efficacy and limitations. Areas covered Patients with progressive skeletal dysplasia often need to undergo orthopedic surgical interventions in the first two decades of life. Recently, we have treated four patients with a new surgery to correct progressive tracheal obstruction. Enzyme replacement therapy (ERT) has been approved clinically. Cell-based therapies such as hematopoietic stem cell therapy (HSCT) and gene therapy are typically one-time, permanent treatments for enzyme deficiencies. We report here on four Morquio A patients treated with HSCT approved in Japan and followed for at least ten years after treatment. Gene therapy is under investigation on mouse models but not yet available as a therapeutic option. Expert opinion ERT and HSCT in combination with surgical intervention(s) are a therapeutic option for Morquio A; however, the approach for bone and cartilage lesion remains an unmet challenge. PMID:28217429

Quantitative measurement and analysis for detection and treatment planning of developmental dysplasia of the hip

NASA Astrophysics Data System (ADS)

Liu, Xin; Lu, Hongbing; Chen, Hanyong; Zhao, Li; Shi, Zhengxing; Liang, Zhengrong

2009-02-01

Developmental dysplasia of the hip is a congenital hip joint malformation affecting the proximal femurs and acetabulum that are subluxatable, dislocatable, and dislocated. Conventionally, physicians made diagnoses and treatments only based on findings from two-dimensional (2D) images by manually calculating clinic parameters. However, anatomical complexity of the disease and the limitation of current standard procedures make accurate diagnosis quite difficultly. In this study, we developed a system that provides quantitative measurement of 3D clinical indexes based on computed tomography (CT) images. To extract bone structure from surrounding tissues more accurately, the system firstly segments the bone using a knowledge-based fuzzy clustering method, which is formulated by modifying the objective function of the standard fuzzy c-means algorithm with additive adaptation penalty. The second part of the system calculates automatically the clinical indexes, which are extended from 2D to 3D for accurate description of spatial relationship between femurs and acetabulum. To evaluate the system performance, experimental study based on 22 patients with unilateral or bilateral affected hip was performed. The results of 3D acetabulum index (AI) automatically provided by the system were validated by comparison with 2D results measured by surgeons manually. The correlation between the two results was found to be 0.622 (p<0.01).

Novel pathogenic ACAN variants in non-syndromic short stature patients.

PubMed

Hu, Xuyun; Gui, Baoheng; Su, Jiasun; Li, Hongdou; Li, Niu; Yu, Tingting; Zhang, Qinle; Xu, Yufei; Li, Guoqiang; Chen, Yulin; Qing, Yanrong; Li, Chuan; Luo, Jingsi; Fan, Xin; Ding, Yu; Li, Juan; Wang, Jian; Wang, Xiumin; Chen, Shaoke; Shen, Yiping

2017-06-01

Pathogenic variants of ACAN have been reported to cause spondyloepiphyseal dysplasia Kimberley type, spondyloepimetaphyseal dysplasia, familial osteochondritis dissecans and idiopathic short stature with normal to advanced bone age. A recent international cohort study significantly expanded the ACAN mutation spectrum, further delineated the heterogeneous clinical characteristics of ACAN mutation patients. The prevalence of ACAN mutation in short stature patients is yet unknown. Here we set to assess the frequency of ACAN variants among a cohort of 218 Chinese children with non-syndromic short stature. We identified three novel truncating variants at the 5' end of ACAN gene. All these pathogenic variants co-segregate with severe short stature phenotype in families. In addition, none of the probands showed significant advanced bone age. All affected individuals showed no signs of significant dysmorphic features or skeletal abnormities. The prevalence of ACAN defect in this cohort is estimated to be 1.4% (3/218). It is higher among families with parents also affected with severe short stature, up to 7.0% (3/43) if parental height is <2.5 SD or 16.7% (3/18) if parental height is <3.0 SD. Our data suggest that ACAN mutation is a relative common cause of familial severe short stature. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of Bone Targeting Drugs.

PubMed

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Mackenzie, William G; Mason, Robert W; Orii, Tadao; Tomatsu, Shunji

2017-06-23

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca 2+ . The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments.

Development of Bone Targeting Drugs

PubMed Central

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J.; Mackenzie, William G.; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

2017-01-01

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca2+. The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments. PMID:28644392

Dwarfism in Alaskan malamutes: a disease resembling metaphyseal dysplasia in human beings.

PubMed Central

Sande, R. D.; Alexander, J. E.; Spencer, G. R.; Padgett, G. A.; Davis, W. C.

1982-01-01

In a study of 300 Alaskan Malamutes, dwarfism was shown to be an autosomal recessive inherited disease with complete penetrance that resulted in disturbed endochondral bone formation. Osseous growth disturbance was manifest at the metaphyses of tubular bones. Clinical and radiographic changes were very similar to those of rickets, although appositional bone formation rates were normal. Serum calcium, phosphorus, and alkaline phosphatase were within normal limits. Urinary excretion of calcium, phosphate, and amino acids were normal. Excess matrix was formed in the zone of cartilage cell proliferation, and the matrix persisted in the growth plate. Normal stresses resulted in microfractures in the metaphyses with subsequent interference of vascular penetration into the zone of degenerated cartilage cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:7065114

IgG4 related disease - a retrospective descriptive study highlighting Canadian experiences in diagnosis and management.

PubMed

Patel, Harshna; Khalili, Korosh; Kyoung, Kim Tae; Yazdi, Leyla; Lee, Eric; May, Gary; Kortan, Paul; Coltescu, Catalina; Hirschfield, Gideon M

2013-12-09

Appreciating the utility of published diagnostic criteria for autoimmune pancreatitis, when compared to the characteristics of patients clinically managed as having disease, informs and refines ongoing clinical practice. Comparative retrospective descriptive evaluation of patients with autoimmune pancreatitis including dedicated radiology review. 66 subjects with radiographic OR clinical features of autoimmune pancreatitis were initially identifiable (Male: n = 50), with 55 confirmed for evaluation. The most common presentation included pain (67%), weight loss (65%), and jaundice (62%). Diffuse enlargement of the pancreas was evident in 38%, whilst multifocal, focal, or atrophic changes were seen in 7%, 33% and 9% respectively. 13% had no pancreatic parenchymal involvement. Peripheral rim enhancement was seen in 23 patients (42%). Where discernible, disease was a) Sclerosing pancreatitis and cholangitis, n = 21; b) Sclerosing cholangitis, n = 9; c) Sclerosing pancreatitis, n = 4; d) Sclerosing pancreatitis and cholangitis with pancreatic pseudotumour, n = 7; e) Sclerosing cholangitis with hepatic pseudotumour, n = 3; f) Sclerosing pancreatitis with pancreatic pseudotumour, n = 1. 56% of the patients had systemic manifestations and the median serum IgG4 at diagnosis was 5.12 g/L. The Korean criteria identified most patients (82%) compared to HISORt (55%) or the Japan Pancreas Society (56%). The majority (HISORt 60%; Japan Pancreas Society 55%; Korean 58%) met diagnostic criterion by radiological findings and elevated serum IgG4. Treatment and response did not differ when stratified by diagnostic criteria. Our descriptive and retrospective dataset confirms that in non-expert practice settings, autoimmune pancreatitis scoring systems with a focus on radiology and serology capture most patients who are clinically felt to have disease.

Whole-genome sequencing of Atacama skeleton shows novel mutations linked with dysplasia.

PubMed

Bhattacharya, Sanchita; Li, Jian; Sockell, Alexandra; Kan, Matthew J; Bava, Felice A; Chen, Shann-Ching; Ávila-Arcos, María C; Ji, Xuhuai; Smith, Emery; Asadi, Narges B; Lachman, Ralph S; Lam, Hugo Y K; Bustamante, Carlos D; Butte, Atul J; Nolan, Garry P

2018-04-01

Over a decade ago, the Atacama humanoid skeleton (Ata) was discovered in the Atacama region of Chile. The Ata specimen carried a strange phenotype-6-in stature, fewer than expected ribs, elongated cranium, and accelerated bone age-leading to speculation that this was a preserved nonhuman primate, human fetus harboring genetic mutations, or even an extraterrestrial. We previously reported that it was human by DNA analysis with an estimated bone age of about 6-8 yr at the time of demise. To determine the possible genetic drivers of the observed morphology, DNA from the specimen was subjected to whole-genome sequencing using the Illumina HiSeq platform with an average 11.5× coverage of 101-bp, paired-end reads. In total, 3,356,569 single nucleotide variations (SNVs) were found as compared to the human reference genome, 518,365 insertions and deletions (indels), and 1047 structural variations (SVs) were detected. Here, we present the detailed whole-genome analysis showing that Ata is a female of human origin, likely of Chilean descent, and its genome harbors mutations in genes ( COL1A1 , COL2A1 , KMT2D , FLNB , ATR , TRIP11 , PCNT ) previously linked with diseases of small stature, rib anomalies, cranial malformations, premature joint fusion, and osteochondrodysplasia (also known as skeletal dysplasia). Together, these findings provide a molecular characterization of Ata's peculiar phenotype, which likely results from multiple known and novel putative gene mutations affecting bone development and ossification. © 2018 Bhattacharya et al.; Published by Cold Spring Harbor Laboratory Press.

Role of Carbamazepine in the Symptomatic Treatment of Subacute Sclerosing Panencephalitis: A Case Report and Review of the Literature

PubMed Central

Ravikumar, Sandhya; Crawford, John Ross

2013-01-01

We describe the clinical presentation and clinical course of subacute sclerosing panencephalitis in a 13-year-old previously healthy boy who recently immigrated to the United States from Iraq. He presented with macular retinopathy, followed by progressive myoclonus and encephalopathy. After extensive workup, a diagnosis of subacute sclerosing panencephalitis was suspected by the presence of period epileptiform discharges on electroencephalogram and confirmed by elevated measles titers in the cerebrospinal fluid. Combination immunomodulatory therapy with isoprinosine, ribavirin, and intra-Ommaya interferon alpha did not result in clinical improvement. Within days following the administration of carbamazepine, there was remarkable improvement in the myoclonus and he was able to ambulate independently for a period of 4 months at which time he unfortunately progressed to a vegetative state. This case highlights the importance of carbamazepine as a potential first line symptomatic treatment of subacute sclerosing panencephalitis and provides a review of the literature on the subject. PMID:23533854

Subacute sclerosing panencephalitis (SSPE) presenting as acute disseminated encephalomyelitis in a child.

PubMed

Goraya, Jatinder; Marks, Harold; Khurana, Divya; Legido, Agustin; Melvin, Joseph

2009-07-01

Subacute sclerosing panencephalitis (SSPE) typically presents with progressive mental deterioration, behavioral changes, and myoclonic jerks. Atypical presentations are not unknown and may result in diagnostic delays. A 9-year-old girl presented with poor balance and ataxia following an episode of upper respiratory tract infection. Neurological examination revealed mild hemiparesis and ataxia. Brain magnetic resonance imaging revealed scattered areas of T2 and fluid-attenuated inversion recovery hyperintensities in the white matter consistent with acute disseminated encephalomyelitis. Despite treatment with intravenous methylprednisolone, intravenous immunoglobulins, and plasmapheresis, progressive neurological worsening occurred. Later during the course of her illness, subacute sclerosing panencephalitis was suspected from the appearance of burst-suppression pattern on electroencephalogram, and the diagnosis confirmed by elevated titers of measles antibodies in cerebrospinal fluid. Physicians taking care of children need to be aware of atypical presentations of subacute sclerosing panencephalitis and must have a high index of suspicion to prevent diagnostic delays and avoid unnecessary diagnostic and therapeutic interventions.

Cutaneous Squamous Cell Carcinoma With Sclerosing Features: An Uncommon and Potentially Aggressive Variant.

PubMed

Ronen, Shira; Gru, Alejandro A; Noland, Mary M; Rowe, David M; Wick, Mark R

2018-05-08

Sclerosing squamous cell carcinoma (SCC), also known as "desmoplastic" SCC, is a rare subtype of cutaneous malignancy. This variant is clinically significant because it is associated with an increased risk of local recurrence and metastasis. We herein present 16 examples of sclerotic SCC of the skin in 8 men and 3 women, with a median age of 66 years. The most common site of origin for this tumor is the skin of the head and neck, including the scalp (5 tumors in 2 different patients), forehead (3 cases), nasal ala (2 cases), neck (2 cases in the same patient), ear (2 cases), cheek (1 case), and chest (1 case). Microscopically, sclerosing SCCs are characterized by cellular cords, nests, and islands, as well as scattered single cells infiltrating densely desmoplastic and collagenized connective tissue. The differential diagnosis principally includes sclerosing basal cell carcinoma, microcystic adnexal carcinoma, and desmoplastic trichoepithelioma. The main goals of this study are to further characterize these lesions pathologically, and increase general awareness of this SCC subtype.

[Kenny-Caffey syndrome and its related syndromes].

PubMed

Isojima, Tsuyoshi; Kitanaka, Sachiko

2015-11-01

Kenny-Caffey syndrome (KCS) is a very rare dysmorphologic syndrome characterized by proportionate short stature, cortical thickening and medullary stenosis of tubular bones, delayed closure of anterior fontanelle, eye abnormalities, and hypoparathyroidism. Two types of KCS were known: the autosomal recessive form (KCS type 1), which is caused by mutations of the TBCE gene, and the autosomal dominant form (KCS type 2), which is caused by mutations of the FAM111A gene. TBCE mutation also causes hypoparathyroidism-retardation-dysmorphism syndrome, and FAM111A mutation also causes gracile bone dysplasia. These two diseases can be called as KCS-related syndromes. In this article, we review the clinical manifestations of KCS and discuss its related syndromes.

Sclerosant extravasation as a complication of sclerosing endotherapy for bleeding gastric varices.

PubMed

Cheng, H-C; Cheng, P-N; Tsai, Y-M; Tsai, H-M; Chen, C-Y

2004-03-01

We report here the case of a 65-year-old woman who suffered intraperitoneal sclerosant leakage after endoscopic injection sclerotherapy for bleeding gastric varices. In total, 3 ml of N-butyl-2-cyanoacrylate and Lipiodol mixture was injected. The patient developed mild fever and pain over the left upper quadrant and flank after the procedure. In addition to a Lipiodol-filled gastric varix, the imaging studies disclosed a wide spread of Lipiodol over the left peritoneal cavity. The patient was kept fasting with parenteral antibiotics and nutrition. She responded well to the treatment, and all of the symptoms had subsided 6 days later.

[POEMS syndrome with plasmocytoma lytic bone lesion].

PubMed

Rafai, M A; Fadel, H; Boulaajaj, F Z; Sibai, M; Rafai, M; El Moutawakkil, B; Bourezgui, M; Trafeh, M; Slassi, I

2008-01-01

Crow-Fukase or Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes syndrome (POEMS) is a rare multisystemic affection with incompletely elucidated etiopathogenesis. We report a case of POEMS syndrome in a 48-year-old adult revealed four months before admission by areflexic flask tetraparesis prevalent on the lower limbs in connection with demyelinating and axonal CIDP "like" sensoriomotor neuropathy of the four limbs electroneuromyographically. The patient presented elevated protein level in the CSF with monoclonal standard IgG gammapathy associated with a narrow band lambda, suggesting POEMS syndrome. Further explorations revealed skin lesions with glomeruloid angiomas, edematous vasomotor disorders as well as erythrocyanose, hypogonadism, papillar edema and a lytic bone lesion of the left scapula. Radiotherapy was associated with corticosteroids and plasma exchanges. Outcome was good with resolution of the symptoms and stabilization of the neuropathy. POEMS syndrome is rare; the diagnosis is based on necessary criteria, the presence of a demyelinating and axonal polyneuropathy associated with an IgA or IgG monoclonal gammapathy, the light chain being almost entirely lambda, associated to other characteristic elements, in particular glomeruloid angiomas, endocrinopathy, sclerosing plasmocytoma which must be carefully required. Treatment is based on surgical cure or radiotherapy for bone lesion and non specific treatments such as corticosteroid therapy, plasma exchanges and IVIG.

Metaphyseal chondrodysplasia.

PubMed Central

Spranger, J. W.

1977-01-01

Any review of the metaphyseal chondrodysplasias is complicated by their variety and mainly unknown pathogenesis. The more familiar types display considerable clinical and radiological diversity: even more so the rarer disorders which still require complete definition, but differences in their mode of inheritance make diagnostic precision mandatory. These dysplasias present in infancy or in childhood, when the patient, usually dwarfed, may be proportionate, so that some forms may be confused with rickets or other lesions. Mental retardation is unusual, but the skin, hair, nails and facies provide valuable diagnostic features. Radiological abnormalities mainly affect the metaphyses of the shortened limb bones, less often the skull, vertebrae, pelvis, ribs and extremities, and sometimes their distribution may indicate the specific type of dysplasia. In a further complex group multiple systems are involved, notably the pancreas, intestine and lympho-reticular, causing malabsorption and haematological or immunological disorders. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:335375

Multidisciplinary team approach in the oral rehabilitation of patients with cleidocranial dysplasia to achieve a functional aesthetic outcome.

PubMed

Patel, D; Patel, N; Brennan, P A; Kwok, J

2017-11-01

Cleidocranial dysplasia is a hereditary congenital disorder that results in delayed ossification of midline structures, and is caused by mutations in the RunX2 (runt-related transcription factor 2) gene located on the short arm of chromosome 6. Successful treatment depends on multidisciplinary assessment and a comprehensive staged treatment plan. We present a case series of 12 patients who were managed with a specifically tailored combination of surgery, orthodontics, and prosthodontics to provide a functional dentition and restore their smile and facial contour. Successful dental rehabilitation can be challenging in this group because patients often have multiple dental anomalies and a reduced quantity and density of alveolar bone. Rehabilitation with early intervention and a carefully planned multidisciplinary approach has been successful in the long term. Copyright © 2017 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

A close look at EEG in subacute sclerosing panencephalitis.

PubMed

Demir, Nurhak; Cokar, Ozlem; Bolukbasi, Feray; Demirbilek, Veysi; Yapici, Zuhal; Yalcinkaya, Cengiz; Direskeneli, Guher Saruhan; Yentur, Sibel; Onal, Emel; Yilmaz, Gulden; Dervent, Aysin

2013-08-01

To define atypical clinical and EEG features of patients with subacute sclerosing panencephalitis that may require an overview of differential diagnosis. A total of 66 EEGs belonging to 53 (17 females and 36 males) consecutive patients with serologically confirmed subacute sclerosing panencephalitis were included in this study. Patient files and EEG data were evaluated retrospectively. EEGs included in the study were sleep-waking EEGs and/or sleep-waking video-EEG records with at least 2 hours duration. Cranial MRIs of the patients taken 2 months before or after the EEG records were included. Age range at the onset of the disease was 15 to 192 months (mean age: 80.02 months). Epilepsy was diagnosed in 21 (43%) patients. Among epileptic seizures excluding myoclonic jerks, generalized tonic-clonic type constituted the majority (58%). Tonic seizures were documented during the video-EEG recordings in four patients. Epileptogenic activities were found in 56 (83%) EEG recordings. They were localized mainly in frontal (58%), posterior temporal, parietal, occipital (26%), and centrotemporal (8%) regions. Multiple foci were detected in 26 recordings (39%). Epileptiform activities in the 39 (59%) EEGs appeared as unilateral or bilateral diffuse paroxysmal discharges. Recognition of uncommon clinical and EEG findings of subacute sclerosing panencephalitis, especially in countries where subacute sclerosing panencephalitis has not been eliminated yet, could be helpful in prevention of misdiagnosis and delay in the management of improvable conditions.

Achondroplasia: Development, pathogenesis, and therapy.

PubMed

Ornitz, David M; Legeai-Mallet, Laurence

2017-04-01

Autosomal dominant mutations in fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia (Ach), the most common form of dwarfism in humans, and related chondrodysplasia syndromes that include hypochondroplasia (Hch), severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), and thanatophoric dysplasia (TD). FGFR3 is expressed in chondrocytes and mature osteoblasts where it functions to regulate bone growth. Analysis of the mutations in FGFR3 revealed increased signaling through a combination of mechanisms that include stabilization of the receptor, enhanced dimerization, and enhanced tyrosine kinase activity. Paradoxically, increased FGFR3 signaling profoundly suppresses proliferation and maturation of growth plate chondrocytes resulting in decreased growth plate size, reduced trabecular bone volume, and resulting decreased bone elongation. In this review, we discuss the molecular mechanisms that regulate growth plate chondrocytes, the pathogenesis of Ach, and therapeutic approaches that are being evaluated to improve endochondral bone growth in people with Ach and related conditions. Developmental Dynamics 246:291-309, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Total hip arthroplasty in patients with dwarfism.

PubMed

Sekundiak, Todd D

2005-09-01

Skeletal dysplasia or dwarfism presents in a host of manners. Degenerative hip disease can present as a primary problem secondary to the abnormal growth disturbance or secondarily from the abnormal load distributions through the hip joint itself. Total hip arthroplasty is a successful procedure but sought with increased risks and complications when compared to routine hip arthroplasty. Custom or modular hip implants can help a surgeon manage the abnormal bone morphology seen with this condition.

High-Dose Intravenous Ribavirin Therapy for Subacute Sclerosing Panencephalitis

PubMed Central

Hosoya, Mitsuaki; Shigeta, Shiro; Mori, Shuichi; Tomoda, Akemi; Shiraishi, Seiji; Miike, Teruhisa; Suzuki, Hitoshi

2001-01-01

Two patients with subacute sclerosing panencephalitis (SSPE) were treated safely and effectively with high doses of intravenous ribavirin combined with intraventricular alpha interferon. The ribavirin concentrations maintained in the serum and cerebrospinal fluid were higher than those which inhibit SSPE virus replication in vitro and in vivo. PMID:11181386

Role of apparent diffusion coefficients with diffusion-weighted magnetic resonance imaging in differentiating between benign and malignant bone tumors.

PubMed

Wang, Tingting; Wu, Xiangru; Cui, Yanfen; Chu, Caiting; Ren, Gang; Li, Wenhua

2014-11-29

Benign and malignant bone tumors can present similar imaging features. This study aims to evaluate the significance of apparent diffusion coefficients (ADC) in differentiating between benign and malignant bone tumors. A total of 187 patients with 198 bone masses underwent diffusion-weighted (DW) magnetic resonance (MR) imaging. The ADC values in the solid components of the bone masses were assessed. Statistical differences between the mean ADC values in the different tumor types were determined by Student's t-test. Histological analysis showed that 84/198 (42.4%) of the bone masses were benign and 114/198 (57.6%) were malignant. There was a significant difference between the mean ADC values in the benign and malignant bone lesions (P<0.05). However, no significant difference was found in the mean ADC value between non-ossifying fibromas, osteofibrous dysplasia, and malignant bone tumors. When an ADC cutoff value≥1.10×10(-3) mm2/s was applied, malignant bone lesions were excluded with a sensitivity of 89.7%, a specificity of 84.5%, a positive predictive value of 82.6%, and a negative predictive value of 95.3%. The combination of DW imaging with ADC quantification and T2-weighted signal characteristics of the solid components in lesions can facilitate differentiation between benign and malignant bone tumors.

Reconstruction of the Shallow Acetabulum With a Combination of Autologous Bulk and Impaction Bone Grafting Fixed by Cement.

PubMed

Maruyama, Masaaki; Wakabayashi, Shinji; Ota, Hiroshi; Tensho, Keiji

2017-02-01

Acetabular bone deficiency, especially proximal and lateral deficiency, is a difficult technical problem during primary total hip arthroplasty (THA) in developmental dysplasia of the hip (DDH). We report a new reconstruction method using a medial-reduced cemented socket and additional bulk bone in conjunction with impaction morselized bone grafting (additional bulk bone grafting method). In a population of patients with acetabular dysplasia undergoing THA using a medial-reduced cemented socket and additional bulk bone with impacted morselized bone grafting, we evaluated (1) the radiographic appearance of bone graft; (2) the proportion of cups that developed loosening and subsequent revision; and (3) clinical results (outcome scores and complications). Forty percent of 330 THAs for DDH performed at one center between 1999 and 2009 were defined as shallow dysplastic hips. The additional bulk bone grafting method was performed on 102 THAs with shallow acetabulum (31% for DDH) at one center between 1999 and 2009. We used this approach and technique for shallow acetabuli when a cup protruded from the lateral acetabular edge in preoperative templating. The other 132 dysplastic hips without bone grafting had THA performed at the same periods and served as a control. Acetabuli were defined as shallow when the depth was less than or equal to one-fifth of the pelvic height (cranial-caudal length on radiograph). The additional bulk bone grafting technique was as follows: the resected femoral head was sectioned at 1 to 2 cm thickness, and a suitable size of the bulk bone graft was placed on the lateral iliac cortex and fixed by poly-L-lactate absorbable screws. Autologous impaction morselized bone grafting, with or without hydroxyapatite granules, was performed along with the implantation of a medial-reduced cemented socket. We defined an "incorporated" graft as remodeling and trabeculation including rounding off of the protruding edge of a graft beyond the socket. Radiographic criteria used for determining loosening were migration or a continuous radiolucent zone between the prosthesis/bone cement and host bone. Clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) and the Merle d'Aubigne and Postel score; complications were tallied from chart review. The followup was 10 ± 3 years (range, 6-15 years). One acetabular component (1%) with severe shallow and steep acetabuli showed definite radiographic evidence of loosening and was revised. Clinically, the mean JOA score for the hips treated with additional bulk bone grafting THA in this study improved from 39 ± 10 points preoperatively to 95 ± 5 points postoperatively (p < 0.05, paired t-test). The mean Merle d'Aubigne and Postel score for the hips improved from 7 ± 2 points to 17 ± 1 points (p < 0.05, paired t-test). Complications included a Trendelenburg sign in one hip, dislocation in one, and transient partial sciatic nerve palsy in one. Within 3 years 6 months postoperatively, 101 of 102 additional bulk bone grafting cases showed successful bone remodeling and bone graft reorientation without collapse on radiographs. Partial resorption of the additional bone graft on the lateral side was observed in two hips (2%) with socket abduction angles of < 35°. Achieving stable acetabular fixation is often challenging in the dysplastic hip, especially shallow acetabulum, and a variety of techniques have been described. Early results of combining bulk graft with impaction of morselized graft are promising. Although each surgical technique was well established, further investigation for clinical results of a combination of these techniques might be necessary to confirm longer term outcomes. Level IV, therapeutic study.

Friend or foe: high bone mineral density on routine bone density scanning, a review of causes and management.

PubMed

Gregson, Celia L; Hardcastle, Sarah A; Cooper, Cyrus; Tobias, Jonathan H

2013-06-01

A finding of high BMD on routine DXA scanning is not infrequent and most commonly reflects degenerative disease. However, BMD increases may also arise secondary to a range of underlying disorders affecting the skeleton. Although low BMD increases fracture risk, the converse may not hold for high BMD, since elevated BMD may occur in conditions where fracture risk is increased, unaffected or reduced. Here we outline a classification for the causes of raised BMD, based on identification of focal or generalized BMD changes, and discuss an approach to guide appropriate investigation by clinicians after careful interpretation of DXA scan findings within the context of the clinical history. We will also review the mild skeletal dysplasia associated with the currently unexplained high bone mass phenotype and discuss recent advances in osteoporosis therapies arising from improved understanding of rare inherited high BMD disorders.

Friend or foe: high bone mineral density on routine bone density scanning, a review of causes and management

PubMed Central

Hardcastle, Sarah A.; Cooper, Cyrus; Tobias, Jonathan H.

2013-01-01

A finding of high BMD on routine DXA scanning is not infrequent and most commonly reflects degenerative disease. However, BMD increases may also arise secondary to a range of underlying disorders affecting the skeleton. Although low BMD increases fracture risk, the converse may not hold for high BMD, since elevated BMD may occur in conditions where fracture risk is increased, unaffected or reduced. Here we outline a classification for the causes of raised BMD, based on identification of focal or generalized BMD changes, and discuss an approach to guide appropriate investigation by clinicians after careful interpretation of DXA scan findings within the context of the clinical history. We will also review the mild skeletal dysplasia associated with the currently unexplained high bone mass phenotype and discuss recent advances in osteoporosis therapies arising from improved understanding of rare inherited high BMD disorders. PMID:23445662

Central Cemento-Ossifying Fibroma: Primary Odontogenic or Osseous Neoplasm?

PubMed

Woo, Sook-Bin

2015-12-01

Currently, central cemento-ossifying fibroma is classified by the World Health Organization as a primary bone-forming tumor of the jaws. However, histopathologically, it is often indistinguishable from cemento-osseous dysplasias in that it forms osteoid and cementicles (cementum droplets) in varying proportions. It is believed that pluripotent cells within the periodontal membrane can be stimulated to produce either osteoid or woven bone and cementicles when stimulated. If this is true, cemento-ossifying fibroma would be better classified as a primary odontogenic neoplasm arising from the periodontal ligament. Cemento-ossifying fibromas also do not occur in the long bones. The present report compares several entities that fall within the diagnostic realm of benign fibro-osseous lesions and reviews the evidence for reclassifying central cemento-ossifying fibroma as a primary odontogenic neoplasm. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Cemento-ossifying Fibroma Of Paranasal Sinus Presenting Acutely As Orbital Cellulitis.

PubMed

Khanna, Maneesh; Buddhavarapu, Shanker Rao; Hussain, Sheik Akbar; Amir, Emran

2009-01-01

Fibro-osseous lesions of the face and paranasal sinuses are relatively uncommon. These lesions have overlapping clinical, radiologic and pathologic features causing difficulty in diagnosis. Neoplastic fibro-osseous paranasal sinus lesions can be benign or malignant. The benign fibro-osseous lesions described are: ossifying fibroma (and its histologic variants) and fibrous dysplasia. The variants of ossifying fibroma differ in the nature of calcified material (i.e. cementum versus bone), in the location of the lesion (oral versus paranasal sinus or orbital), other morphologic variations (presence of psammomatoid concretions) and biologic behavior (aggressive versus stable). Presence of cementum or bone classifies the lesion as cementifying fibroma or ossifying fibroma respectively while lesions with mixture of both cementum and bone are called cemento-ossifying fibroma. We describe a case of a young adult male with cemento-ossifying fibroma of paranasal sinus presenting acutely as left orbital cellulitis with proptosis.

Cemento-ossifying Fibroma Of Paranasal Sinus Presenting Acutely As Orbital Cellulitis

PubMed Central

Khanna, Maneesh; Buddhavarapu, Shanker Rao; Hussain, Sheik Akbar; Amir, Emran

2009-01-01

Fibro-osseous lesions of the face and paranasal sinuses are relatively uncommon. These lesions have overlapping clinical, radiologic and pathologic features causing difficulty in diagnosis. Neoplastic fibro-osseous paranasal sinus lesions can be benign or malignant. The benign fibro-osseous lesions described are: ossifying fibroma (and its histologic variants) and fibrous dysplasia. The variants of ossifying fibroma differ in the nature of calcified material (i.e. cementum versus bone), in the location of the lesion (oral versus paranasal sinus or orbital), other morphologic variations (presence of psammomatoid concretions) and biologic behavior (aggressive versus stable). Presence of cementum or bone classifies the lesion as cementifying fibroma or ossifying fibroma respectively while lesions with mixture of both cementum and bone are called cemento-ossifying fibroma. We describe a case of a young adult male with cemento-ossifying fibroma of paranasal sinus presenting acutely as left orbital cellulitis with proptosis. PMID:22470655

[Custom-made implant for complex facial reconstruction: A case of total replacement of temporo-mandibular joint, zygomatic arch and malar bone].

PubMed

Guillier, D; Moris, V; See, L-A; Girodon, M; Wajszczak, B-L; Zwetyenga, N

2017-02-01

Total prosthetic replacement of the temporo-mandibular joint (TMJ) has become a common procedure, but it is usually limited to the TMJ itself. We report about one case of complex prosthetic joint reconstruction extending to the neighbouring bony structures. A 57-year-old patient, operated several times for a cranio-facial fibrous dysplasia, presented with a recurring TMJ ankylosis and a complexe latero-facial bone loss on the right side. We performed a reconstruction procedure including the TMJ, the zygomatic arch and the malar bone by mean of custom made composite prosthesis (chrome-cobalt-molybdenum-titanium and polyethylene). Five years postoperatively, mouth opening, nutrition, pain and oral hygiene were significantly improved. Nowadays technical possibilities allow for complex facial alloplastic reconstructions with good medium term results. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Periapical cemento-osseous dysplasia: a case report with twelve-year follow-up and review of literature.

PubMed

Senia, E S; Sarao, M S

2015-11-01

To present a case report describing the long-term behaviour of periapical cemento-osseous dysplasia by observing the radiographic changes that took place over a period of 12 years. A review of the pertinent literature is also presented. A healthy 26-year-old white female was referred to the Wilford Hall USAF Medical Center Endodontic Department for evaluation of an asymptomatic radiolucency at the apex of the right mandibular lateral incisor. Following a clinical evaluation that included pulp testing, a diagnosis of periapical cemento-osseous dysplasia (PCOD) was made. No treatment was rendered but follow-up visits were recommended. The patient was subsequently re-evaluated 8 times over a period of 12 years. During that time the lesion changed in appearance, displaying the various phases of PCOD. At the same time, lesions affecting the three adjoining incisors appeared and behaved in a similar manner. At the 12-year recall, the right lateral and both central incisors revealed no evidence of PCOD and an almost normal trabecular pattern of bone could be seen. Misdiagnosis and unnecessary treatment of PCOD may be avoided with careful pulp testing and knowledge of its most common locations of occurrence, radiographic appearances (phases) and benign behaviour. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Air contamination in the sclerosing foam for the treatment of varicose veins.

PubMed

de Franciscis, S; Nobile, Cga; Larosa, E; Montemurro, R; Serra, R

2016-03-01

Fluids and drugs formulated for intravenous infusion may potentially promote the growth of microorganisms that can cause infections. The aim of this study is to test the sterility of sclerosing foam. Polidocanol was used for the production of the foam. The Tessari method was used in order to generate the foam. The preparation was carried out both in the operating theater and in an outpatient room. A validation test with microorganisms was also performed. The measurements showed no evident growth of microorganisms and in the validation tests the foam appeared to even display bacteriostatic and/or bactericide properties. Sclerosing foam seems to be safe from a microbiological point of view. © The Author(s) 2014.

Adult fulminant subacute sclerosing panencephalitis: pathological and molecular studies--a case report.

PubMed

Souraud, J B; Faivre, A; Waku-Kouomou, D; Gaillard, T; Aouad, N; Meaudre, E; Wild, F T; Fouet, B; Soulard, R

2009-01-01

Subacute sclerosing panencephalitis is an uncommon progressive neurological disorder caused by a persistent defective measles virus, typically affecting children. We describe a case of fulminant subacute sclerosing panencephalitis in a 25-year-old male. Brain tissue biopsy showed histologic evidence of encephalitis with eosinophilic intranuclear inclusion bodies (Cowdry Type A and B), intracytoplasmic inclusion bodies, perivascular lymphoplasmacytic infiltration and gliosis. Immunohistochemical studies were positive using an anti-measles antibody. Reverse transcriptase-PCR detected measles virus RNA and phylogenetic analysis indicated a C2 genotype. The rare adult-onset form is often atypical and difficult to diagnose and should be included in the differential diagnosis of subacute "unexplained" neurological diseases and uncommon infectious disorders.

Brainstem involvement in subacute sclerosing panencephalitis.

PubMed

Sharma, Pawan; Singh, Dileep; Singh, Maneesh Kumar; Garg, Ravindra Kumar; Kohli, Neera

2011-01-01

The parieto-occipital region of the brain is most frequently and severely affected in subacute sclerosing panencephalitis (SSPE). The basal ganglia, cerebellum and corpus callosum are less commonly involved. Brainstem involvement is rarely described in SSPE, and usually there is involvement of other regions of the brain. We describe a patient with subacute sclerosing panencephalitis with brain magnetic resonance imaging showing extensive brainstem involvement without significant involvement of other cortical structures. Though rarely described in SSPE, one should be aware of such brainstem and cerebellum involvement, and SSPE should be kept in mind when brainstem signal changes are seen in brain MRI with or without involvement of other regions of brain to avoid erroneous reporting.

C-type natriuretic peptide plasma levels are elevated in subjects with achondroplasia, hypochondroplasia, and thanatophoric dysplasia.

PubMed

Olney, Robert C; Prickett, Timothy C R; Espiner, Eric A; Mackenzie, William G; Duker, Angela L; Ditro, Colleen; Zabel, Bernhard; Hasegawa, Tomonobu; Kitoh, Hiroshi; Aylsworth, Arthur S; Bober, Michael B

2015-02-01

C-type natriuretic peptide (CNP) is a crucial regulator of endochondral bone growth. In a previous report of a child with acromesomelic dysplasia, Maroteaux type (AMDM), caused by loss-of-function of the CNP receptor (natriuretic peptide receptor-B [NPR-B]), plasma levels of CNP were elevated. In vitro studies have shown that activation of the MAPK kinase (MEK)/ERK MAPK pathway causes functional inhibition of NPR-B. Achondroplasia, hypochondroplasia, and thanatophoric dysplasia are syndromes of short-limbed dwarfism caused by activating mutations of fibroblast growth factor receptor-3, which result in overactivation of the MEK/ERK MAPK pathway. The purpose of this study was to determine whether these syndromes exhibit evidence of CNP resistance as reflected by increases in plasma CNP and its amino-terminal propeptide (NTproCNP). This was a prospective, observational study. Participants were 63 children and 20 adults with achondroplasia, 6 children with hypochondroplasia, 2 children with thanatophoric dysplasia, and 4 children and 1 adult with AMDM. Plasma levels of CNP and NTproCNP were higher in children with achondroplasia with CNP SD scores (SDSs) of 1.0 (0.3-1.4) (median [interquartile range]) and NTproCNP SDSs of 1.4 (0.4-1.8; P < .0005). NTproCNP levels correlated with height velocity. Levels were also elevated in adults with achondroplasia (CNP SDSs of 1.5 [0.7-2.1] and NTproCNP SDSs of 0.5 [0.1-1.0], P < .005). In children with hypochondroplasia, CNP SDSs were 1.3 (0.7-1.5) (P = .08) and NTproCNP SDSs were 1.9 (1.8-2.3) (P < .05). In children with AMDM, CNP SDSs were 1.6 (1.4-3.3) and NTproCNP SDSs were 4.2 (2.7-6.2) (P < .01). In these skeletal dysplasias, elevated plasma levels of proCNP products suggest the presence of tissue resistance to CNP.

Three-Dimensional Magnetic Resonance Imaging of Glenohumeral Dysplasia in Neonatal Brachial Plexus Palsy.

PubMed

Eismann, Emily A; Laor, Tal; Cornwall, Roger

2016-01-20

Existing quantitative measurements of glenohumeral dysplasia in children with unresolved neonatal brachial plexus palsy (NBPP) have been mostly limited to the axial plane. The purpose of this study was to describe the three-dimensional (3D) pathoanatomy of glenohumeral dysplasia using 3D magnetic resonance imaging (MRI) reformations. 3D MRI reformations of the scapula, glenoid labrum, and proximal part of the humerus were created from a volume-acquisition proton-density-weighted MRI sequence of both the affected and the unaffected shoulder of seventeen children less than six years of age with unresolved NBPP who had not undergone shoulder surgery. Glenoid retroversion and posterior humeral head displacement were measured on axial 2D images. Humeral head displacement in all planes, labral circumference, glenoid retroversion, glenoid declination, and scapular morphometric values were measured on 3D reformations. Contiguity of the humeral head with the labrum and the shape of the glenoid were classified. Measurements were compared between the affected and unaffected sides. On 3D evaluation, the humeral head was completely posteriorly translated in ten patients but was never outside the glenoid labrum. Instead, in these patients, the humeral head was eccentrically articulating with the dysplastic glenoid and was contained by a posteriorly elongated labrum. Glenoid dysplasia was not limited to the axial plane. Less declination of the glenoid in the coronal plane correlated with greater 3D glenoid retroversion. Glenoid retroversion resulted from underdevelopment of the posterior aspect of the glenoid rather than overdevelopment of the anterior aspect of the glenoid. 3D measurements of greater glenoid retroversion and less declination correlated with 2D measurements of glenoid retroversion and posterior humeral head displacement. Posterior humeral head displacement in NBPP should not be considered a simple "dislocation." Glenohumeral dysplasia is not limited to the axial plane. Abnormal glenoid declination may have potential implications for the evaluation and treatment of shoulder weakness and contractures. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Sclerosing encapsulating peritonitis: a case series.

PubMed

Nandedkar, Shirish; Malukani, Kamal; Nayak, Renu; Patidar, Ekta

2014-03-01

Sclerosing encapsulating peritonitis (SEP) is a relatively rare cause of intestinal obstruction characterized by total or partial encapsulation of the small intestine by a thick fibrous membrane and is a difficult preoperative diagnosis. A series of seven cases of SEP is reported. Modalities of preoperative diagnosis along with clinical presentation, operative findings, and histopathology are discussed.

An evaluation of subacute sclerosing panencephalitis patients with diffusion-weighted magnetic resonance imaging.

PubMed

Abuhandan, M; Cece, H; Calik, M; Karakas, E; Dogan, F; Karakas, O

2013-03-01

This study aimed to evaluate the contribution of diffusion weighted magnetic resonance imaging to the diagnosis and staging of subacute sclerosing panencephalitis. The study comprised 26 patients diagnosed with subacute sclerosing panencephalitis at our clinic who were undergoing regular follow-up, and a control group of 18 subjects. Clinical staging was determined by Risk and Haddad classification; 12 at Stage II and 14 at Stage III. Diffusion weighted magnetic resonance images were taken of six areas (frontal, parieto-occipital, cerebellar, deep white matter, thalamus and basal ganglia) and by calculating the apparent diffusion coefficient (ADC) values, and a comparison was made between the stages and with the control group. The ADC values of all the areas of the subacute sclerosing panencephalitis patients were found to be significantly higher compared to the control group (p < 0.05). While the mean ADC values of the deep white matter, basal ganglia, frontal and parieto-occipital areas of the Stage II patients were found to be significant compared to the control group (p < 0.05), there was no significance in the other areas (p > 0.05). The ADC values of all the areas of the Stage III patients were found to be significantly high compared to the Stage II values (p < 0.05). Diffusion weighted magnetic resonance imaging can be used with other diagnostic criteria to confirm diagnosis of subacute sclerosing panencephalitis and to reveal differences between the stages.

An unusual case of acute encephalitic syndrome: Is it acute measles encephalitis or subacute sclerosing panencephalitis?

PubMed

Garg, Ravindra K; Malhotra, Hardeep S; Rizvi, Imran; Kumar, Neeraj; Jain, Amita

2017-01-01

Subacute sclerosing panencephalitis is a late complication of measles infection and develops usually 6 to 15 years after the primary measles infection. Fulminant subacute sclerosing panencephalitis is an infrequently encountered form wherein the disease rapidly progresses to death. A six-year old male child presented with fever, abnormal movements of the left side of body followed by weakness of the left side of the body, and involuntary abnormal movements of right upper and lower limbs. On examination, he was drowsy and was unable to communicate. He had right-sided hemiballismus. He also had left-sided hemiparesis and the left plantar reflex was extensor. Cerebrospinal fluid examination revealed elevated protein and cells. In the serum and cerebrospinal fluid, anti-measles IgG antibodies were found to be positive. No other viral marker was noted in the cerebrospinal fluid. Magnetic resonance imaging of the brain showed extensive damage to the right temporal, parietal, and to a lesser extent, the frontal region as well as subcortical structures of these regions. Electroencephalography revealed generalized slowing of waves. Over a period of the next 3 days, the intensity and frequency of choreiform movements markedly reduced and the patient developed periodic generalized myoclonus, which was predominantly present on the right side. The patient succumbed to his illness and died after one month. Fulminant subacute sclerosing panencephalitis may have unusual clinical manifestations such as hemiballismus. In fulminant subacute sclerosing panencephalitis, neuroimaging may show extensive cortical damage.

A retrospective 3- to 5-year study of the reconstruction of oral function using implant-supported prostheses in patients with hypohidrotic ectodermal dysplasia.

PubMed

Zou, Duohong; Wu, Yiqun; Wang, Xu Dong; Huang, Wei; Zhang, Zhiyong; Zhang, Zhiyuan

2014-10-01

The aim of this study was to evaluate oral function rehabilitation in patients with hypohidrotic ectodermal dysplasia (HED) using implant-supported prostheses based on bone augmentation. From September 2005 and March 2009, 25 HED patients were chosen for clinical data analysis in this study. The criteria for patient selection included the following: the display of clinical features of HED, the number of congenitally missing teeth (>5), the patient age (>16 years), the patient's willingness, and the patient's tolerance for bone graft surgery and implant placement. Follow-up evaluations were initiated from the time of implant prosthetic placement and scheduled annually for 3-5 years. The effects of oral function reconstruction were assessed based on the cumulative survival and success rates of implants, the health of the peri-implant area, and the degree of patient satisfaction. Twenty-five HED patients received 169 conventional implants and 10 zygomatic implants (179 total implants). During 3-5 years of post-loading evaluations, 5 of the 179 implants failed and 3 implants were removed. The 3-year success and cumulative survival rates were 97.2% and 98.3%, respectively. Furthermore, periodontal probing and radiographic assessments showed that the 3-year incidence of peri-implantitis was 4.5%. Finally, HED patients expressed high degrees of satisfaction with their facial contours, masticatory function, pronunciation ability, and comfort with the implant-supported prostheses. The results of this 3- to 5-year retrospective study indicate that the oral function of HED patients can be effectively reconstructed using bone augmentation and implant-supported prostheses; however, longer term results are warranted in the future.

Sclerostin Antibody Improves Skeletal Parameters in a Brtl/+ Mouse Model of Osteogenesis Imperfecta†

PubMed Central

Sinder, Benjamin P.; Eddy, Mary M.; Ominsky, Michael S; Caird, Michelle S.; Marini, Joan C.; Kozloff, Kenneth M.

2012-01-01

Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by osteopenia and easy susceptibility to fracture. Symptoms are most prominent during childhood. Although anti-resorptive bisphosphonates have been widely used to treat pediatric OI, controlled trials showed improved vertebral parameters but equivocal effects on long-bone fracture rates. New treatments for OI are needed to increase bone mass throughout the skeleton. Sclerostin antibody (Scl-Ab) therapy is potently anabolic in the skeleton by stimulating osteoblasts via the canonical wnt signaling pathway, and may be beneficial for treating OI. In this study, Scl-Ab therapy was investigated in mice heterozygous for a typical OI-causing Gly->Cys substitution in col1a1. Two weeks of Scl-Ab successfully stimulated osteoblast bone formation in Brtl/+ and WT mice, leading to improved bone mass and reduced long-bone fragility. Image-guided nanoindentation revealed no alteration in local tissue mineralization dynamics with Scl-Ab. These results contrast with previous findings of antiresorptive efficacy in OI both in mechanism and potency of effects on fragility. In conclusion, short-term Scl-Ab was successfully anabolic in osteoblasts harboring a typical OI-causing collagen mutation and represents a potential new therapy to improve bone mass and reduce fractures in pediatric OI. PMID:22836659

Biliary tract instillation of a SMAC mimetic induces TRAIL-dependent acute sclerosing cholangitis-like injury in mice

PubMed Central

Guicciardi, Maria Eugenia; Krishnan, Anuradha; Bronk, Steven F; Hirsova, Petra; Griffith, Thomas S; Gores, Gregory J

2017-01-01

Primary sclerosing cholangitis (PSC) is a cholestatic liver disease of unknown etiopathogenesis characterized by fibrous cholangiopathy of large and small bile ducts. Systemic administration of a murine TNF-related apoptosis-inducing ligand (TRAIL) receptor agonist induces a sclerosing cholangitis injury in C57BL/6 mice, suggesting endogenous TRAIL may contribute to sclerosing cholangitis syndromes. Cellular inhibitor of apoptosis proteins (cIAP-1 and cIAP-2) are negative regulators of inflammation and TRAIL receptor signaling. We hypothesized that if endogenous TRAIL promotes sclerosing cholangitis, then cIAP depletion should also induce this biliary tract injury. Herein, we show that cIAP protein levels are reduced in the interlobular bile ducts of human PSC livers. Downregulation of cIAPs in normal human cholangiocytes in vitro by use of a SMAC mimetic (SM) induces moderate, ripoptosome-mediated apoptosis and RIP1-independent upregulation of proinflammatory cytokines and chemokines. Cytokine and chemokine expression was mediated by the non-canonical activation of NF-κB. To investigate whether downregulation of cIAPs is linked to generation of a PSC-like phenotype, an SM was directly instilled into the mouse biliary tree. Twelve hours after biliary instillation, TUNEL-positive cholangiocytes were identified; 5 days later, PSC-like changes were observed in the SM-treated mice, including a fibrous cholangiopathy of the interlobular bile ducts, portal inflammation, significant elevation of serum markers of cholestasis and cholangiographic evidence of intrahepatic biliary tract injury. In contrast, TRAIL and TRAIL-receptor deficient mice showed no sign of cholangiopathy following SM intrabiliary injection. We conclude that in vivo antagonism of cIAPs in mouse biliary epithelial cells is sufficient to trigger cholangiocytes apoptosis and a proinflammatory response resulting in a fibrous cholangiopathy resembling human sclerosing cholangitis. Therefore, downregulation of cIAPs in PSC cholangiocytes may contribute to the development of the disease. Our results also indicate that inhibition of TRAIL signaling pathways may be beneficial in the treatment of PSC. PMID:28055006

Less promising results with sclerosing ethoxysclerol injections for midportion achilles tendinopathy: a retrospective study.

PubMed

van Sterkenburg, Maayke N; de Jonge, Milko C; Sierevelt, Inger N; van Dijk, C Niek

2010-11-01

Local injections of the sclerosing substance polidocanol (Ethoxysclerol) have shown good clinical results in patients with chronic midportion Achilles tendinopathy. After training by the inventors of the technique, sclerosing Ethoxysclerol injections were applied on a group of patients in our center. Sclerosing Ethoxysclerol injections will yield good results in the majority of patients. Case series; Level of evidence, 4. In 113 patients (140 tendons) with Achilles tendinopathy, we identified 62 patients (70 tendons) showing neovascularization on color Doppler ultrasound. Fifty-three Achilles tendons (48 patients) were treated with sclerosing Ethoxysclerol injections, with intervals of 6 weeks and a maximum of 5 sessions. Treatment was completed when neovascularization or pain had disappeared, or when there was no positive treatment effect after 3 to 4 sessions. Forty-eight patients (20 women and 28 men) with a median age of 45 years, (range, 33-68 years) were treated. Median symptom duration was 23 months (range, 3-300 months). Fifty-three tendons were treated with a median of 3 sessions of Ethoxysclerol injections. Six weeks after the last injection, 35% of patients had no complaints, 9% had minimal symptoms, 42% were the same, and 14% had more complaints. Women were 3.8 times (95% confidence interval: 1.1-13.8) more likely to have unsatisfactory outcome than men. Pain correlated positively with neovessels on ultrasound (P < .01). At 2.7 to 5.1 year follow-up, 53% had received additional (surgical/conservative) treatment; 3 of these patients (7.5%) still had complaints of Achilles tendinopathy. In 6 patients, complaints that were still present 6 weeks after treatment had resolved spontaneously by final follow-up. Our study did not confirm the high beneficial value of sclerosing neovascularization in patients with midportion Achilles tendinopathy. Despite the retrospective design of our study, we consider it important to stress that injection of Ethoxysclerol may not be as promising as was thought.

Novel Somatic Mutation in LEMD3 Splice Site Results in Buschke-Ollendorff Syndrome with Polyostotic Melorheostosis and Osteopoikilosis.

PubMed

Gutierrez, Daniel; Cooper, Kevin D; Mitchell, Anna L; Cohn, Heather I

2015-01-01

Buschke-Ollendorff syndrome is a rare autosomal dominant disorder caused by loss of function in LEMD3, resulting in connective tissue nevi and varying bone dysplasia. Although typically benign, we describe a novel LEMD3 splice site mutation (IVS12 + 1delG) in a 13-year-old boy with Buschke-Ollendorff syndrome presenting with severe skeletal deformities, polyostotic melorheostosis, and osteopoikilosis. © 2015 Wiley Periodicals, Inc.

Rapidly Growing Brtl/+ Mouse Model of Osteogenesis Imperfecta Improves Bone Mass and Strength with Sclerostin Antibody Treatment

PubMed Central

Sinder, Benjamin P.; Salemi, Joseph D.; Ominsky, Michael S.; Caird, Michelle S.; Marini, Joan C.; Kozloff, Kenneth M.

2014-01-01

Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk that presents most severely in children. Anti-resorptive bisphosphonates are frequently used to treat pediatric OI and controlled clinical trials have shown bisphosphonate therapy improves vertebral outcomes but has little benefit on long bone fracture rate. New treatments which increase bone mass throughout the pediatric OI skeleton would be beneficial. Sclerostin antibody (Scl-Ab) is a potential candidate anabolic therapy for pediatric OI and functions by stimulating osteoblastic bone formation via the canonical wnt signaling pathway. To explore the effect of Scl-Ab on the rapidly growing OI skeleton, we treated rapidly growing 3 week old Brtl/+ mice, harboring a typical heterozygous OI-causing Gly->Cys substitution on col1a1, for 5 weeks with Scl-Ab. Scl-Ab had anabolic effects in Brtl/+ and led to new cortical bone formation and increased cortical bone mass. This anabolic action resulted in improved mechanical strength to WT Veh levels without altering the underlying brittle nature of the material. While Scl-Ab was anabolic in trabecular bone of the distal femur in both genotypes, the effect was less strong in these rapidly growing Brtl/+ mice compared to WT. In conclusion, Scl-Ab was able to stimulate bone formation in a rapidly growing Brtl/+ murine model of OI, and represents a potential new therapy to improve bone mass and reduce fracture risk in pediatric OI. PMID:25445450

Osteopathia striata with cranial sclerosis: clinical, radiological, and bone histological findings in an adolescent girl.

PubMed

Ward, L M; Rauch, F; Travers, R; Roy, M; Montes, J; Chabot, G; Glorieux, F H

2004-08-15

Osteopathia striata with cranial sclerosis (OS-CS) is a rare skeletal dysplasia characterized by linear striations of the long bones, osteosclerosis of the cranium, and extra-skeletal anomalies. We provide a comprehensive description of the skeletal phenotype in a French-Canadian girl with a moderate to severe form of sporadic OS-CS. Multiple medical problems, including anal stenosis and the Pierre-Robin sequence, were evident in the first few years of life. At 14 years, she was fully mobile, with normal intellect and stature. She suffered chronic lower extremity pain in the absence of fractures, as well as severe headaches, unilateral facial paralysis, and bilateral mixed hearing loss. Biochemical indices of bone and mineral metabolism were within normal limits. Bone densitometry showed increased areal bone mineral density in the skull, trunk, and pelvis, but not in the upper and lower extremities. An iliac bone biopsy specimen revealed an increased amount of trabecular bone. Trabeculae were abnormally thick, but there was no evidence of disturbed bone remodeling. In a cranial bone specimen, multiple layers of periosteal bone were found that covered a compact cortical compartment containing tightly packed haversian canals. Bone lamellation was normal in both the iliac and skull samples. Osteoclast differentiation studies showed that peripheral blood osteoclast precursors from this patient formed functional osteoclasts in vitro. Thus, studies of bone metabolism did not explain why bone mass is increased in most skeletal areas of this patient. Cranial histology points to exuberant periosteal bone formation as a potential cause of the cranial sclerosis.

The genetic implication of scoliosis in osteogenesis imperfecta: a review

PubMed Central

Liu, Gang; Chen, Jia; Zhou, Yangzhong; Zuo, Yuzhi; Liu, Sen; Chen, Weisheng

2017-01-01

Osteogenesis imperfecta (OI) is a kind of heritable connective tissue disorder, including blue sclerae, hearing loss, skeletal dysplasia causing bone fragility and deformities. It is typically caused by collagen related gene mutations, which could lead to bone formation abnormalities. Scoliosis is one of the most common and severe spinal phenotype which has been reported in approximately 26–74.5% of all OI patients. Recent breakthroughs have suggested that OI can be divided into more than 16 types based on genetic mutations with different degrees of scoliosis. In this review, we summarize the etiology of scoliosis in OI, especially the genetic studies of different types. We aim to provide a systematic review of the genetic etiology and clinical suggestions of scoliosis in OI. PMID:29354746

Case Report and Molecular Analysis of Subacute Sclerosing Panencephalitis in a South African Child

PubMed Central

Vardas, Eftyhia; Leary, P. M.; Yeats, Jane; Badrodien, Waseila; Kreis, Stephanie

1999-01-01

This is the first case of subacute sclerosing panencephalitis from South Africa in which the molecular characteristics of the causative measles virus were examined. The virus found is classified as genotype D3, which has not previously been found in Africa and was last circulating in the United States before 1992. PMID:9986851

Subacute Sclerosing Panencephalitis: The Foothold in Undervaccination.

PubMed

Holt, Rebecca L; Kann, Dylan; Rassbach, Caroline E; Schwenk, Hayden T; Ritter, Jana M; Rota, Paul A; Elbers, Jorina

2016-12-01

Subacute sclerosing panencephalitis (SSPE) is a fatal complication of measles infection. We present a case of a fully vaccinated 3-year-old boy who was diagnosed with and treated for autoimmune encephalitis before arriving at a diagnosis of SSPE. We discuss the challenges of diagnosing SSPE in developed countries. Copyright © 2016 Elsevier Inc. All rights reserved.

Sclerosing cholangitis and intracranial lymphoma in a child with classical Wiskott-Aldrich syndrome.

PubMed

Vignesh, Pandiarajan; Suri, Deepti; Rawat, Amit; Lau, Yu Lung; Bhatia, Anmol; Das, Ashim; Srinivasan, Anirudh; Dhandapani, Sivashanmugam

2017-01-01

Patients with Wiskott-Aldrich syndrome (WAS) are predisposed to malignancy and autoimmunity in addition to infections. We report a male child with WAS, who had presented with recurrent pneumonia, eczema, thrombocytopenia, autoimmune hemolytic anemia, and vasculitic skin lesions. Genetic analysis revealed a classical genotype WAS 155C>T; R41X. At 2 years of follow-up, he developed persistent headache and progressive hepatomegaly. Brain imaging showed a mass in the right frontal region, which on histopathology was shown to be high-grade non-Hodgkin lymphoma. Magnetic resonance cholangiopancreatography showed features of sclerosing cholangitis. This report extends the clinical spectrum and highlights unusual manifestations of sclerosing cholangitis and intracranial lymphoma in a patient with WAS. © 2016 Wiley Periodicals, Inc.

Blindness, dancing extremities, and corpus callosum and brain stem involvement: an unusual presentation of fulminant subacute sclerosing panencephalitis.

PubMed

Singhi, Pratibha; Saini, Arushi Gahlot; Sankhyan, Naveen; Gupta, Pankaj; Vyas, Sameer

2015-01-01

A 4-year-old girl presented with acute visual loss followed 2 weeks later with loss of speech and audition, fulminant neuroregression, and choreo-athetoid movements of extremities. Fundus showed bilateral chorioretinitis. Electroencephalography showed periodic complexes. Measles antibody titers were elevated in both serum and cerebrospinal fluid, consistent with subacute sclerosing panencephalitis. Neuroimaging showed discontiguous involvement of splenium of the corpus callosum and ventral pons with sparing of cortical white matter. Our case highlights the atypical clinical and radiologic presentations of subacute sclerosing panencephalitis. Pediatricians need to be aware that necrotizing chorioretinitis in a child and/or atypical brain stem changes could be the heralding feature of this condition in endemic countries. © The Author(s) 2014.

Pharmacological management of osteogenesis

PubMed Central

Nardone, Valeria; D'Asta, Federica; Brandi, Maria Luisa

2014-01-01

Osteogenesis and bone remodeling are complex biological processes that are essential for the formation of new bone tissue and its correct functioning. When the balance between bone resorption and formation is disrupted, bone diseases and disorders such as Paget's disease, fibrous dysplasia, osteoporosis and fragility fractures may result. Recent advances in bone cell biology have revealed new specific targets for the treatment of bone loss that are based on the inhibition of bone resorption by osteoclasts or the stimulation of bone formation by osteoblasts. Bisphosphonates, antiresorptive agents that reduce bone resorption, are usually recommended as first-line therapy in women with postmenopausal osteoporosis. Numerous studies have shown that bisphosphonates are able to significantly reduce the risk of femoral and vertebral fractures. Other antiresorptive agents indicated for the treatment of osteoporosis include selective estrogen receptor modulators, such as raloxifene. Denosumab, a human monoclonal antibody, is another antiresorptive agent that has been approved in Europe and the USA. This agent blocks the RANK/RANKL/OPG system, which is responsible for osteoclastic activation, thus reducing bone resorption. Other approved agents include bone anabolic agents, such as teriparatide, a recombinant parathyroid hormone that improves bone microarchitecture and strength, and strontium ranelate, considered to be a dual-action drug that acts by both osteoclastic inhibition and osteoblastic stimulation. Currently, anti-catabolic drugs that act through the Wnt-β catenin signaling pathway, serving as Dickkopf-related protein 1 inhibitors and sclerostin antagonists, are also in development. This concise review provides an overview of the drugs most commonly used for the control of osteogenesis in bone diseases. PMID:24964310

 Alkaline phosphatase normalization is a biomarker of improved survival in primary sclerosing cholangitis.

PubMed

Hilscher, Moira; Enders, Felicity B; Carey, Elizabeth J; Lindor, Keith D; Tabibian, James H

2016-01-01

 Introduction. Recent studies suggest that serum alkaline phosphatase may represent a prognostic biomarker in patients with primary sclerosing cholangitis. However, this association remains poorly understood. Therefore, the aim of this study was to investigate the prognostic significance and clinical correlates of alkaline phosphatase normalization in primary sclerosing cholangitis. This was a retrospective cohort study of patients with a new diagnosis of primary sclerosing cholangitis made at an academic medical center. The primary endpoint was time to hepatobiliaryneoplasia, liver transplantation, or liver-related death. Secondary endpoints included occurrence of and time to alkaline phosphatase normalization. Patients who did and did not achieve normalization were compared with respect to clinical characteristics and endpoint-free survival, and the association between normalization and the primary endpoint was assessed with univariate and multivariate Cox proportional-hazards analyses. Eighty six patients were included in the study, with a total of 755 patient-years of follow-up. Thirty-eight patients (44%) experienced alkaline phosphatase normalization within 12 months of diagnosis. Alkaline phosphatase normalization was associated with longer primary endpoint-free survival (p = 0.0032) and decreased risk of requiring liver transplantation (p = 0.033). Persistent normalization was associated with even fewer adverse endpoints as well as longer survival. In multivariate analyses, alkaline phosphatase normalization (adjusted hazard ratio 0.21, p = 0.012) and baseline bilirubin (adjusted hazard ratio 4.87, p = 0.029) were the only significant predictors of primary endpoint-free survival. Alkaline phosphatase normalization, particularly if persistent, represents a robust biomarker of improved long-term survival and decreased risk of requiring liver transplantation in patients with primary sclerosing cholangitis.

Rare bone diseases and their dental, oral, and craniofacial manifestations.

PubMed

Foster, B L; Ramnitz, M S; Gafni, R I; Burke, A B; Boyce, A M; Lee, J S; Wright, J T; Akintoye, S O; Somerman, M J; Collins, M T

2014-07-01

Hereditary diseases affecting the skeleton are heterogeneous in etiology and severity. Though many of these conditions are individually rare, the total number of people affected is great. These disorders often include dental-oral-craniofacial (DOC) manifestations, but the combination of the rarity and lack of in-depth reporting often limit our understanding and ability to diagnose and treat affected individuals. In this review, we focus on dental, oral, and craniofacial manifestations of rare bone diseases. Discussed are defects in 4 key physiologic processes in bone/tooth formation that serve as models for the understanding of other diseases in the skeleton and DOC complex: progenitor cell differentiation (fibrous dysplasia), extracellular matrix production (osteogenesis imperfecta), mineralization (familial tumoral calcinosis/hyperostosis hyperphosphatemia syndrome, hypophosphatemic rickets, and hypophosphatasia), and bone resorption (Gorham-Stout disease). For each condition, we highlight causative mutations (when known), etiopathology in the skeleton and DOC complex, and treatments. By understanding how these 4 foci are subverted to cause disease, we aim to improve the identification of genetic, molecular, and/or biologic causes, diagnoses, and treatment of these and other rare bone conditions that may share underlying mechanisms of disease. © International & American Associations for Dental Research.

Rare Bone Diseases and Their Dental, Oral, and Craniofacial Manifestations

PubMed Central

Foster, B.L.; Ramnitz, M.S.; Gafni, R.I.; Burke, A.B.; Boyce, A.M.; Lee, J.S.; Wright, J.T.; Akintoye, S.O.; Somerman, M.J.; Collins, M.T.

2014-01-01

Hereditary diseases affecting the skeleton are heterogeneous in etiology and severity. Though many of these conditions are individually rare, the total number of people affected is great. These disorders often include dental-oral-craniofacial (DOC) manifestations, but the combination of the rarity and lack of in-depth reporting often limit our understanding and ability to diagnose and treat affected individuals. In this review, we focus on dental, oral, and craniofacial manifestations of rare bone diseases. Discussed are defects in 4 key physiologic processes in bone/tooth formation that serve as models for the understanding of other diseases in the skeleton and DOC complex: progenitor cell differentiation (fibrous dysplasia), extracellular matrix production (osteogenesis imperfecta), mineralization (familial tumoral calcinosis/hyperostosis hyperphosphatemia syndrome, hypophosphatemic rickets, and hypophosphatasia), and bone resorption (Gorham-Stout disease). For each condition, we highlight causative mutations (when known), etiopathology in the skeleton and DOC complex, and treatments. By understanding how these 4 foci are subverted to cause disease, we aim to improve the identification of genetic, molecular, and/or biologic causes, diagnoses, and treatment of these and other rare bone conditions that may share underlying mechanisms of disease. PMID:24700690

Melorheostosis and central giant cell granuloma of the mandible in a 15-year-old girl.

PubMed

Anderson, K M; Shintaku, W H; Rosebush, M S; Rawal, Y B; Woodard, E S

2013-11-01

Melorheostosis is a nonhereditary bone dysplasia primarily affecting the appendicular skeleton. Because clinical and histologic features are often nonspecific, the diagnosis is often based on the radiographic presentation. Involvement of the craniofacial skeleton is rare. We describe a case of a 15-year-old girl with appendicular and craniofacial melorheostosis with adjacent central giant cell granuloma. We discuss the possible significance of this previously unreported finding. Copyright © 2013 Elsevier Inc. All rights reserved.

Sclerotherapy for 'scrotal cysts' using tetracycline instillation.

PubMed

Courtney, S P; Wightman, J A

1991-04-01

Aspiration and tetracycline (Achromycin) instillation has been used to sclerose 'scrotal cysts'. Thirteen hydroceles and epididymal cysts were treated. Of the cysts treated, four failed to sclerose, and moderate to severe pain occurred in eight patients. In three patients the pain was severe, necessitating admission to the hospital. We would not recommend this treatment either in terms of efficacy or for patient comfort.

External bone marrow cytological examination quality assurance (EQAhem)--summary after 6 years in Poland.

PubMed

Lewandowski, Krzysztof; Kurpierz, Katarzyna; Sledzinska, Anna

2015-10-01

Bone marrow macroscopic examination remains one of the most difficult and subjective laboratory assessments in hematology. Only a few external quality assurance programs in the field are present worldwide. We have developed an external quality assurance program EQAhem that allows assessment of the whole process of bone marrow examination. The program participants assess blood and bone marrow smears from the patient, identify selected cells from photographs provided to them, and interpret the microscopic results. In this article, the results of the EQAhem program in Poland from 6 years are summarized. During this time, 62 labs were assessed in total, and positive results were achieved by 89.25 % labs, taking into account all tests. Correct responses with respect to the percentage of cell count were provided by ca. 77.5 % labs. Slightly worse results were obtained when megakaryocyte count and cell identification from photographs were tested. The worst results were obtained in case of dysplasia assessment and clinical interpretation of microscopic examination (54.1 and 58.6 % correct responses, respectively). EQAhem delivers precise information about the quality of bone marrow examinations performed in Poland and has a substantial educational value. We believe that after 6 years, EQAhem has significantly improved the quality of bone marrow microscopic examinations performed in Poland.

Mutations in PCYT1A cause spondylometaphyseal dysplasia with cone-rod dystrophy.

PubMed

Yamamoto, Guilherme L; Baratela, Wagner A R; Almeida, Tatiana F; Lazar, Monize; Afonso, Clara L; Oyamada, Maria K; Suzuki, Lisa; Oliveira, Luiz A N; Ramos, Ester S; Kim, Chong A; Passos-Bueno, Maria Rita; Bertola, Débora R

2014-01-02

Spondylometaphyseal dysplasia with cone-rod dystrophy is a rare autosomal-recessive disorder characterized by severe short stature, progressive lower-limb bowing, flattened vertebral bodies, metaphyseal involvement, and visual impairment caused by cone-rod dystrophy. Whole-exome sequencing of four individuals affected by this disorder from two Brazilian families identified two previously unreported homozygous mutations in PCYT1A. This gene encodes the alpha isoform of the phosphate cytidylyltransferase 1 choline enzyme, which is responsible for converting phosphocholine into cytidine diphosphate-choline, a key intermediate step in the phosphatidylcholine biosynthesis pathway. A different enzymatic defect in this pathway has been previously associated with a muscular dystrophy with mitochondrial structural abnormalities that does not have cartilage and/or bone or retinal involvement. Thus, the deregulation of the phosphatidylcholine pathway may play a role in multiple genetic diseases in humans, and further studies are necessary to uncover its precise pathogenic mechanisms and the entirety of its phenotypic spectrum. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Matrilin-3 Is Dispensable for Mouse Skeletal Growth and Development

PubMed Central

Ko, Yaping; Kobbe, Birgit; Nicolae, Claudia; Miosge, Nicolai; Paulsson, Mats; Wagener, Raimund; Aszódi, Attila

2004-01-01

Matrilin-3 belongs to the matrilin family of extracellular matrix (ECM) proteins and is primarily expressed in cartilage. Mutations in the gene encoding human matrilin-3 (MATN-3) lead to autosomal dominant skeletal disorders, such as multiple epiphyseal dysplasia (MED), which is characterized by short stature and early-onset osteoarthritis, and bilateral hereditary microepiphyseal dysplasia, a variant form of MED characterized by pain in the hip and knee joints. To assess the function of matrilin-3 during skeletal development, we have generated Matn-3 null mice. Homozygous mutant mice appear normal, are fertile, and show no obvious skeletal malformations. Histological and ultrastructural analyses reveal endochondral bone formation indistinguishable from that of wild-type animals. Northern blot, immunohistochemical, and biochemical analyses indicated no compensatory upregulation of any other member of the matrilin family. Altogether, our findings suggest functional redundancy among matrilins and demonstrate that the phenotypes of MED disorders are not caused by the absence of matrilin-3 in cartilage ECM. PMID:14749384

Severe florid cemento-osseous dysplasia: a case report treated conservatively and literature review.

PubMed

Sarmento, Dmitry José de Santana; Monteiro, Bárbara Vanessa de Brito; de Medeiros, Ana Miryam Costa; da Silveira, Ericka Janine Dantas

2013-03-01

Florid cemento-osseous dysplasia (FCOD) has been described as a condition that characteristically affects the jaws of middle-aged black women. Radiographically, FCOD appears as dense, lobulated masses, often symmetrically located in various regions of the jaws. FCOD is usually asymptomatic. In severe cases, focal expansion may occur due to infection. Management of the symptomatic patient is more difficult due to the avascular nature of the lesion which contributes to susceptibility severe infection, bone sequestration, and osteomyelitis when surgery is performed. This paper presents a rare case of severe FCOD; the black woman patient was diagnosed based on clinical and radiographic findings and treated conservatively. The examination of panoramic radiographs revealed a multiple sclerotic masses with radiolucent borders, found in the mandible and maxilla which were symmetrical at presentation. The patient continuous with the follow-up. This report confirms that a diagnosis can be made with accurate clinical and radiographic assessment. The correct selection of treatment for FCOD depends on this information.

Sclerosing lymphangitis of the penis associated with marked penile oedema and skin erosions.

PubMed

Karray, Mehdi; Litaiem, Noureddine; Jones, Mariem; Zeglaoui, Faten

2017-07-27

Sclerosing lymphangitis of the penis is a benign, under-reported condition consisting of a asymptomatic firm cord-like swelling around the coronal sulcus of the penis usually affecting men in the second or third decade of life. Penile oedema and erosions are rarely reported. Clinical signs may be remarkable contrasting with the self-limited character of the disease. We report a new case of sclerosing lymphangitis of the penis occurring in a 59-year-old patient marked by penile swelling and several overlying skin erosions, and discuss the clinical features and the pathogenesis aspects of the disease. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Strontium Ranelate Reduces the Fracture Incidence in a Growing Mouse Model of Osteogenesis Imperfecta.

PubMed

Shi, Changgui; Hu, Bo; Guo, Lei; Cao, Peng; Tian, Ye; Ma, Jun; Chen, Yuanyuan; Wu, Huiqiao; Hu, Jinquan; Deng, Lianfu; Zhang, Ying; Yuan, Wen

2016-05-01

Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by brittle bones with increased fracture risk. Although current treatment options to improve bone strength in OI focus on antiresorptive bisphosphonates, controlled clinical trials suggest they have an equivocal effect on reducing fracture risk. Strontium ranelate (SrR) is a promising therapy with a dual mode of action that is capable of simultaneously maintaining bone formation and reducing bone resorption, and may be beneficial for the treatment of OI. In this study, SrR therapy was investigated to assess its effects on fracture frequency and bone mass and strength in an animal model of OI, the oim/oim mouse. Three-week-old oim/oim and wt/wt mice were treated with either SrR or vehicle (Veh) for 11 weeks. After treatment, the average number of fractures sustained by SrR-treated oim/oim mice was significantly reduced compared to Veh-treated oim/oim mice. Micro-computed tomographic (μCT) analyses of femurs showed that both trabecular and cortical bone mass were significantly improved with SrR treatment in both genotypes. SrR significantly inhibited bone resorption, whereas bone formation indices were maintained. Biomechanical testing revealed improved bone structural properties in both oim/oim and wild-type (wt/wt) mice under the treatment, whereas no significant effects on bone brittleness and material quality were observed. In conclusion, SrR was able to effectively reduce fractures in oim/oim mice by improving bone mass and strength and thus represents a potential therapy for the treatment of pediatric OI. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.

Rapidly growing Brtl/+ mouse model of osteogenesis imperfecta improves bone mass and strength with sclerostin antibody treatment.

PubMed

Sinder, Benjamin P; Salemi, Joseph D; Ominsky, Michael S; Caird, Michelle S; Marini, Joan C; Kozloff, Kenneth M

2015-02-01

Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk that presents most severely in children. Anti-resorptive bisphosphonates are frequently used to treat pediatric OI and controlled clinical trials have shown that bisphosphonate therapy improves vertebral outcomes but has little benefit on long bone fracture rate. New treatments which increase bone mass throughout the pediatric OI skeleton would be beneficial. Sclerostin antibody (Scl-Ab) is a potential candidate anabolic therapy for pediatric OI and functions by stimulating osteoblastic bone formation via the canonical Wnt signaling pathway. To explore the effect of Scl-Ab on the rapidly growing OI skeleton, we treated rapidly growing 3week old Brtl/+ mice, harboring a typical heterozygous OI-causing Gly→Cys substitution on col1a1, for 5weeks with Scl-Ab. Scl-Ab had anabolic effects in Brtl/+ and led to new cortical bone formation and increased cortical bone mass. This anabolic action resulted in improved mechanical strength to WT Veh levels without altering the underlying brittle nature of the material. While Scl-Ab was anabolic in trabecular bone of the distal femur in both genotypes, the effect was less strong in these rapidly growing Brtl/+ mice compared to WT. In conclusion, Scl-Ab was able to stimulate bone formation in a rapidly growing Brtl/+ murine model of OI, and represents a potential new therapy to improve bone mass and reduce fracture risk in pediatric OI. Copyright © 2014 Elsevier Inc. All rights reserved.

Ligand-Mediated Activation of an Engineered Gs G Protein-Coupled Receptor in Osteoblasts Increases Trabecular Bone Formation

PubMed Central

Hsiao, Edward C.; Millard, Susan M.; Louie, Alyssa; Huang, Yong; Conklin, Bruce R.; Nissenson, Robert A.

2010-01-01

Age-dependent changes in skeletal growth play important roles in regulating skeletal expansion and in the course of many diseases affecting bone. How G protein-coupled receptor (GPCR) signaling affects these changes is poorly understood. Previously, we described a mouse model expressing Rs1, an engineered receptor with constitutive Gs activity. Rs1 expression in osteoblasts from gestation induced a dramatic age-dependent increase in trabecular bone with features resembling fibrous dysplasia; however, these changes were greatly minimized if Rs1 expression was delayed until after puberty. To further investigate whether ligand-induced activation of the Gs-GPCR pathway affects bone formation in adult mice, we activated Rs1 in adult mice with the synthetic ligand RS67333 delivered continuously via an osmotic pump or intermittently by daily injections. We found that osteoblasts from adult animals can be stimulated to form large amounts of bone, indicating that adult mice are sensitive to the dramatic bone- forming actions of Gs signaling in osteoblasts. In addition, our results show that intermittent and continuous activation of Rs1 led to structurally similar but quantitatively different degrees of trabecular bone formation. These results indicate that activation of a Gs-coupled receptor in osteoblasts of adult animals by either intermittent or continuous ligand administration can increase trabecular bone formation. In addition, osteoblasts located at the bone epiphyses may be more responsive to Gs signaling than osteoblasts at the bone diaphysis. This model provides a powerful tool for investigating the effects of ligand-activated Gs-GPCR signaling on dynamic bone growth and remodeling. PMID:20150184

Peripheral cemento-ossifying fibroma: case series literature review.

PubMed

Verma, Esha; Chakki, Arunkumar Bhimashankar; Nagaral, Sharanbasappa Chandrashekar; Ganji, Kiran Kumar

2013-01-01

THE CONCEPT OF FIBROOSSEOUS LESIONS OF BONE HAS EVOLVED OVER THE LAST SEVERAL DECADES AND NOW INCLUDES TWO MAJOR ENTITIES: fibrous dysplasia and ossifying fibroma. Peripheral cemento-ossifying fibroma is a relatively rare tumour classified between fibroosseous lesions. It predominantly affects adolescents and young adults, with peak prevalence between 10 and 19 yrs. The cemento-ossifying fibroma is a central neoplasm of bone as well as periodontium which has caused considerable controversy because of confusion regarding terminology and the criteria for its diagnosis. The cemento-ossifying fibroma is odontogenic in origin, whereas ossifying fibroma is of bony origin. Lesions histologically similar to peripheral ossifying fibroma have been given various names in existing literature. Therefore, we present and discuss in this paper a series of cases of peripheral cemento-ossifying fibroma emphasizing the differential diagnosis.

Chitosan–Sodium Tetradecyl Sulfate Hydrogel: Characterization and Preclinical Evaluation of a Novel Sclerosing Embolizing Agent for the Treatment of Endoleaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zehtabi, Fatemeh; Dumont-Mackay, Vincent; Fatimi, Ahmed

PurposeTo compare the efficacy of an embolization agent with sclerosing properties (made of chitosan and sodium tetradecyl sulfate, CH–STS) with a similar embolization agent but without sclerosing properties (made of chitosan, CH) in treating endoleaks in a canine endovascular aneurysm repair model.MethodsTwo chitosan-based radiopaque hydrogels were prepared, one with STS and one without STS. Their rheological, injectability, and embolizing properties were assessed in vitro; afterwards, their efficacy in occluding endoleaks was compared in a canine bilateral aneurysm model reproducing type I endoleaks (n = 9 each). The primary endpoint was endoleak persistence at 3 or 6 months, assessed on a CT scan andmore » macroscopic examination. Secondary endpoints were the occurrence of stent-graft (SG) thrombosis, the evolution of the aneurysm mean diameter, as well as aneurysm healing and inflammation scores in pathology examinations.ResultsIn vitro experiments showed that both products gelled rapidly and presented initial storage moduli greater than 800 Pa, which increased with time. Both gels were compatible with microcatheter injection and occlude flow up to physiological pressure in vitro. In a type I endoleak model, the injection of CH–STS sclerosing gel tended to reduce the risk of occurrence of endoleaks, compared to CH non-sclerosing agent (2/9 vs. 6/9, p = 0.069). No case of SG thrombosis was observed. Moderate inflammation was found around both gels, with a comparable intensity score in both CH and CH–STS groups (2.6 ± 0.9 and 2.7 ± 0.9, respectively; p = 0.789).ConclusionsFlow occlusion combined with chemical endothelial denudation appears promising for the treatment of endoleaks.Level of EvidenceN/A.« less

Calvarial cleidocraniodysplasia-like defects with ENU-induced Nell-1 deficiency.

PubMed

Zhang, Xinli; Ting, Kang; Pathmanathan, Dharmini; Ko, Theodore; Chen, Weiwei; Chen, Feng; Lee, Haofu; James, Aaron W; Siu, Ronald K; Shen, Jia; Culiat, Cymbeline T; Soo, Chia

2012-01-01

Nell-1, first identified by its overexpression in synostotic cranial sutures, is a novel osteoinductive growth and differentiation factor. To further define Nell-1's role in craniofacial patterning, we characterized defects of the ENU-induced Nell-1-deficient (END) mice, focusing on both intramembranous and endochondral cranial bones. Results showed that calvarial bones of neonatal END mice were reduced in thickness and density, with a phenotype resembling calvarial cleidocraniodysplasia. In addition, a global reduction in osteoblast markers was observed, including reductions in Runx2, alkaline phosphatase, and osteocalcin. Remarkably, detailed analysis of endochondral bones showed dysplasia as well. The chondrocranium in the END mouse showed enrichment for early, proliferating Sox9⁺ chondrocytes, whereas in contrast markers of chondrocytes maturation were reduced. These data suggest that Nell-1 is an important growth factor for regulation of osteochondral differentiation, by regulating both Runx2 and Sox9 expression within the calvarium. In summary, Nell-1 is required for normal craniofacial membranous and endochondral skeletal development.

Asfotase-α improves bone growth, mineralization and strength in mouse models of neurofibromatosis type-1

PubMed Central

de la Croix Ndong, Jean; Makowski, Alexander James; Uppuganti, Sasidhar; Vignaux, Guillaume; Ono, Koichiro; Perrien, Daniel S.; Joubert, Simon; Baglio, Serena R.; Granchi, Donatella; Stevenson, David A.; Rios, Jonathan J.; Nyman, Jeffry S.; Elefteriou, Florent

2014-01-01

Mineralization of the skeleton depends on the balance between levels of pyrophosphate (PPi), an inhibitor of hydroxyapatite formation, and phosphate generated from PPi breakdown by alkaline phosphatase (ALP). We report here that ablation of Nf1, encoding the RAS/GTPase–activating protein neurofibromin, in bone–forming cells leads to supraphysiologic PPi accumulation, caused by a chronic ERK–dependent increase in genes promoting PPi synthesis and extracellular transport, namely Enpp1 and Ank. It also prevents BMP2–induced osteoprogenitor differentiation and, consequently, expression of ALP and PPi breakdown, further contributing to PPi accumulation. The short stature, impaired bone mineralization and strength in mice lacking Nf1 in osteochondroprogenitors or osteoblasts could be corrected by enzyme therapy aimed at reducing PPi concentration. These results establish neurofibromin as an essential regulator of bone mineralization, suggest that altered PPi homeostasis contributes to the skeletal dysplasiae associated with neurofibromatosis type-1 (NF1), and that some of the NF1 skeletal conditions might be preventable pharmacologically. PMID:24997609

Current Care and Investigational Therapies in Achondroplasia.

PubMed

Unger, Sheila; Bonafé, Luisa; Gouze, Elvire

2017-04-01

The goal of this review is to evaluate the management options for achondroplasia, the most common non-lethal skeletal dysplasia. This disease is characterized by short stature and a variety of complications, some of which can be quite severe. Despite several attempts to standardize care, there is still no widely accepted consensus. This is in part due to absence of concrete data on the incidence of sudden unexplained death in infants with achondroplasia and the best investigation for ascertaining which individuals could benefit from foramen magnum decompression surgery. In this review, we identify the different options of care and management for the various orthopedic, neurologic, and respiratory complications. In parallel, several innovative or drug repositioning therapies are being investigated that would restore bone growth but may also prevent complications. Achondroplasia is the most common non-lethal skeletal dysplasia. It is characterized by short stature and a variety of complications, some of which can be quite severe. Despite several attempts to standardize care, there is still no widely accepted consensus. This is in part due to absence of concrete data on the incidence of sudden unexplained death in infants with achondroplasia and the best investigation for ascertaining which individuals could benefit from foramen magnum decompression surgery. In this review, we identify the different options of care and management for the various orthopedic, neurologic, and respiratory complications. In parallel, several innovative or drug repositioning therapies are being investigated that would restore bone growth but may also prevent complications.

Bone marrow-derived mesenchymal stem cells protect against lung injury in a mouse model of bronchopulmonary dysplasia.

PubMed

Luan, Yun; Ding, Wei; Ju, Zhi-Ye; Zhang, Zhao-Hua; Zhang, Xue; Kong, Feng

2015-03-01

The aim of the present study was to investigate the effect of bone marrow‑derived mesenchymal stem cells (BMSCs) in the treatment of lung injury in a mouse model of bronchopulmonary dysplasia (BPD) and examine the underlying mechanisms. A mouse model of BPD was created using continuous exposure to high oxygen levels for 14 days. BMSCs were isolated, cultured and then labeled with green fluorescent protein. Cells (1x106) were subsequently injected intravenously 1 h prior to high oxygen treatment. Animals were randomly divided into three groups (n=5 in each): Control group, BPD model group and BMSC injection group. At two weeks post‑treatment, the expression of transforming growth factor‑β1 (TGF‑β1), vascular endothelial growth factor (VEGF) and von Willebrand factor (vWF) was detected using immunohistochemical staining and immunofluorescence. Compared with the BPD model group, the body weight, airway structure and levels of TGF‑β1 and VEGF were significantly improved in the BMSC‑treated group. Immunofluorescence observations indicated that BMSCs were able to differentiate into cells expressing vWF and VEGF, which are markers of vascular tissues. The present study demonstrated that intravenous injection of BMSCs significantly improved lung damage in a neonatal mouse model of BPD at 14 days following hyperoxia‑induced injury. This provides novel information which may be used to guide further investigation into the use of stem cells in BPD.

The Effect of Neonatal Gene Therapy on Skeletal Manifestations in Mucopolysaccharidosis VII Dogs after a Decade

PubMed Central

Xing, Elizabeth M.; Knox, Van W.; O'Donnell, Patricia A.; Sikura, Tracey; Liu, Yuli; Wu, Susan; Casal, Margret L.; Haskins, Mark E.; Ponder, Katherine P.

2013-01-01

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disease due to deficient activity of β-glucuronidase (GUSB), and results in glycosaminoglycan accumulation. Skeletal manifestations include bone dysplasia, degenerative joint disease, and growth retardation. One gene therapy approach for MPS VII involves neonatal intravenous injection of a gamma retroviral vector expressing GUSB, which results in stable expression in liver and secretion of enzyme into blood at levels predicted to be similar or higher to enzyme replacement therapy. The goal of this study was to evaluate the long-term effect of neonatal gene therapy on skeletal manifestations in MPS VII dogs. Treated MPS VII dogs could walk throughout their lives, while untreated MPS VII dogs could not stand beyond 6 months and were dead by 2 years. Luxation of the coxofemoral joint and the patella, dysplasia of the acetabulum and supracondylar ridge, deep erosions of the distal femur, and synovial hyperplasia were reduced, and the quality of articular bone was improved in treated dogs at 6 to 11 years of age compared with untreated MPS VII dogs at 2 years or less. However, treated dogs continued to have osteophyte formation, cartilage abnormalities, and an abnormal gait. Enzyme activity was found near synovial blood vessels, and there was 2% as much GUSB activity in synovial fluid as in serum. We conclude that neonatal gene therapy reduces skeletal abnormalities in MPS VII dogs, but clinically-relevant abnormalities remain. Enzyme replacement therapy will probably have similar limitations long-term. PMID:23628461

FGFR3 induces degradation of BMP type I receptor to regulate skeletal development.

PubMed

Qi, Huabing; Jin, Min; Duan, Yaqi; Du, Xiaolan; Zhang, Yuanquan; Ren, Fangli; Wang, Yinyin; Tian, Qingyun; Wang, Xiaofeng; Wang, Quan; Zhu, Ying; Xie, Yangli; Liu, Chuanju; Cao, Xu; Mishina, Yuji; Chen, Di; Deng, Chu-xia; Chang, Zhijie; Chen, Lin

2014-07-01

Fibroblast growth factors (FGFs) and their receptors (FGFRs) play significant roles in vertebrate organogenesis and morphogenesis. FGFR3 is a negative regulator of chondrogenesis and multiple mutations with constitutive activity of FGFR3 result in achondroplasia, one of the most common dwarfisms in humans, but the molecular mechanism remains elusive. In this study, we found that chondrocyte-specific deletion of BMP type I receptor a (Bmpr1a) rescued the bone overgrowth phenotype observed in Fgfr3 deficient mice by reducing chondrocyte differentiation. Consistently, using in vitro chondrogenic differentiation assay system, we demonstrated that FGFR3 inhibited BMPR1a-mediated chondrogenic differentiation. Furthermore, we showed that FGFR3 hyper-activation resulted in impaired BMP signaling in chondrocytes of mouse growth plates. We also found that FGFR3 inhibited BMP-2- or constitutively activated BMPR1-induced phosphorylation of Smads through a mechanism independent of its tyrosine kinase activity. We found that FGFR3 facilitates BMPR1a to degradation through Smurf1-mediated ubiquitination pathway. We demonstrated that down-regulation of BMP signaling by BMPR1 inhibitor dorsomorphin led to the retardation of chondrogenic differentiation, which mimics the effect of FGF-2 on chondrocytes and BMP-2 treatment partially rescued the retarded growth of cultured bone rudiments from thanatophoric dysplasia type II mice. Our findings reveal that FGFR3 promotes the degradation of BMPR1a, which plays an important role in the pathogenesis of FGFR3-related skeletal dysplasia. Copyright © 2014 Elsevier B.V. All rights reserved.

Juxta-articular myxoma and intramuscular myxoma are two distinct entities. Activating Gs alpha mutation at Arg 201 codon does not occur in juxta-articular myxoma.

PubMed

Okamoto, Sumika; Hisaoka, Masanori; Meis-Kindblom, Jeanne M; Kindblom, Lars-Gunnar; Hashimoto, Hiroshi

2002-01-01

Juxta-articular myxoma is a rare myxoid tumor of soft tissue that bears a close histologic resemblance to intramuscular myxoma but is distinguished from the latter by its clinical setting and behavior. Activating missense mutations at the Arg 201 codon of the Gs alpha gene ultimately leading to increased levels of cyclic adenosine monophosphate have been implicated in McCune-Albright syndrome and sporadic fibrous dysplasia of bone. Recently, we have demonstrated that the same Gs alpha mutations occur in intramuscular myxomas associated with fibrous dysplasia of bone (Mazabraud's syndrome) as well as in sporadic intramuscular myxoma. The overlapping histologic appearances of juxta-articular myxoma and intramuscular myxoma prompted us to investigate whether there is a relationship between the two entities. We studied this possibility by looking for Gs alpha mutations in juxta-articular myxoma using polymerase chain reaction (PCR) to amplify appropriate genomic DNA fragments extracted from formalin-fixed, paraffin-embedded specimens of five juxta-articular myxomas, followed by single-strand conformation polymorphism analysis. Using these techniques, no aberrant bands were detected in any of the five juxta-articular myxomas, indicating that they lack Gs alpha mutations. Moreover, DNA sequencing of the PCR products of two JAMs showed no abnormalities. We conclude that juxta-articular myxomas, in contrast to intramuscular myxomas, do not involve Arg 201 mutations of the Gs alpha gene, indicating that they represent distinct entities with different underlying molecular mechanisms.

[Immunologic parameters in pericholangitis and primary sclerosing cholangitis with and without ulcerative colitis].

PubMed

Hopf, U; Riecken, E O; Zeitz, M; Eckhardt, R; Lobeck, H; Malchus, R; Möller, B

1983-10-07

Immunological parameters and histocompatibility antigens (HLA) were determined in seven patients with non-bacterial cholangitis. Four patients had pericholangitis and ulcerative colitis, three had primary sclerosing cholangitis, one of these with ulcerative colitis. All 7 patients had antinuclear antibodies; however, there were no antibodies against DNA, against mitochondria or liver membrane antigens. One patient had low-titre rheuma factors. Immunoglobulins G, A and M and complement components C3 and C4 were mostly in the normal range. HLA constellation was positive for B8 in 6 patients. These were male patients with disease manifestations between the 12th and 45th year of life. The results support the concept that pericholangitis and primary sclerosing cholangitis with or without ulcerative colitis are related hepatological disease entities with an immunological pathogenesis and an underlying genetical determination.

Sclerosing polycystic adenosis of the parotid gland presenting with a Warthin tumor.

PubMed

Tokyol, Ciğdem; Aktepe, Fatma; Hastürk, Güler Senyıldız; Yıldız, Hüseyin; Miman, Murat Cem

2012-01-01

Sclerosing polycystic adenosis (SPA) frequently presents as an isolated process, however it may involve adjacent benign salivary gland neoplasia. In this article, we present a 77-year-old female case with a 10-year history of a slow-growing mass of the left parotid gland of SPA presenting with a Warthin tumor. The patient underwent left superficial parotidectomy. The histopathological examination revealed SPA and multifocal Warthin tumor.

Kindler syndrome in a patient with colitis and primary sclerosing cholangitis: coincidence or association?

PubMed

Roda, Ângela; Travassos, Ana Rita; Soares-de-Almeida, Luís; Has, Cristina

2018-03-15

Kindler syndrome is a rare, autosomal recessive genodermatosis, caused by mutations in the FERMT1 gene. It is thought to be primarily a skin disease, but other organs may also be involved. We report a case of a novel mutation of FERMT1 gene in a patient with a probable new phenotype of Kindler syndrome, including colitis and primary sclerosing cholangitis. A 42-year-old man, born to first cousin parents, was referred to our outpatient dermatology clinic with an unknown dermatosis since birth. He presented with neonatal blistering and developed photosensitivity and changes in skin pigmentation during childhood. Since the age of 20, he has had regular follow-up in the gastroenterology clinic, owing to esophageal stenosis, ulcerative colitis, and primary sclerosing cholangitis. Clinical examination revealed jaundice, poikiloderma, diffuse cigarette paper-like atrophy on dorsal surfaces of the hands, and palmoplantar hyperkeratosis. Skin biopsy showed epidermal atrophy covered by orthokeratotic hyperkeratosis. DNA molecular analysis revealed FERMT1 homozygous mutation c.1179G>A, p.W393X, which has not been reported before. The intestinal phenotype of Kindler syndrome has already been defined previously. However, to the best of our knowledge, no other case of primary sclerosing cholangitis in a patient with Kindler syndrome has been reported.

Ellis-van Creveld syndrome: prenatal diagnosis, molecular analysis and genetic counseling.

PubMed

Chen, Chih-Ping; Su, Yi-Ning; Hsu, Chin-Yuan; Chern, Schu-Rern; Tsai, Fuu-Jen; Wu, Pei-Chen; Chen, Po-Tsang; Wang, Wayseen

2010-12-01

To present the perinatal findings and molecular genetic analysis of two siblings with Ellis-van Creveld (EvC) syndrome. A 33-year-old woman, gravida 3, para 1, was referred for genetic counseling at 18 gestational weeks because of recurrent fetal skeletal dysplasia. Two years previously, she had delivered a 1,316-g dead male baby at 28 gestational weeks with a karyotype of 46,XY, postaxial polydactyly of the hands, thoracic narrowness, endocardial cushion defects, transposition of the great arteries, shortening of the long bones, malposition of the toes, and hypoplastic nails. During this pregnancy, prenatal ultrasound at 18 gestational weeks revealed shortening of the long bones (equivalent to 15 weeks), postaxial polydactyly of both hands, thoracic narrowness, and endocardial cushion defects. The pregnancy was subsequently terminated, and a 236-g female fetus was delivered with a karyotype of 46,XX, postaxial polydactyly of the hands, thoracic dysplasia, endocardial cushion defects, shortening of the long bones, and malposition of the toes and hypoplastic nails. The phenotype of each of the two siblings was consistent with EVC syndrome. Molecular analysis of the EVC and EVC2 genes revealed heterozygous mutations in the EVC2 gene. A heterozygous deletion mutation of a 26-bp deletion of c.871-2_894del26 encompassing the junction between intron 7 and exon 8 of the EVC2 gene was found in the mother and two siblings, and a heterozygous nonsense mutation of c.1195C >T, p.R399X in exon 10 of the EVC2 gene was found in the father and two siblings. Prenatal sonographic identification of endocardial cushion defects in association with shortening of the long bones should alert clinicians to the possibility of EvC syndrome and prompt a careful search of hexadactyly of the hands. Molecular analysis of the EVC and EVC2 genes is helpful in genetic counseling in cases with prenatally detected postaxial polydactyly, thoracic narrowness, short limbs and endocardial cushion defects. Copyright © 2010 Taiwan Association of Obstetric & Gynecology. Published by Elsevier B.V. All rights reserved.

Disturbances of bone growth and development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ledesma-Medina, J.; Newman, B.; Oh, K.S.

1988-03-01

''What is growth anyway. Can one talk about positive growth in childhood, neutral growth in maturity, and negative growth in old age. Our goal is to help promote normal positive growth in infants and children. To achieve this, we must be cognizant of the morphologic changes of both normal and abnormal bone formation as they are reflected in the radiographic image of the skeleton. The knowledge of the various causes and the pathophysiologic mechanisms of the disturbances of bone growth and development allows us to recognize the early radiographic manifestations. Endocrine and metabolic disorders affect the whole skeleton, but themore » early changes are best seen in the distal ends of the femurs, where growth rate is most rapid. In skeletal infections and in some vascular injuries two-or three-phase bone scintigraphy supercedes radiography early in the course of the disease. MRI has proved to be very helpful in the early detection of avascular bone necrosis, osteomyelitis, and tumor. Some benign bone tumors and many bone dysplasias have distinct and diagnostic radiographic findings that may preclude further studies. In constitutional diseases of bone, including chromosomal aberrations, skeletal surveys of the patient and all family members together with biochemical and cytogenetic studies are essential for both diagnosis and genetic counseling. Our role is to perform the least invasive and most informative diagnostic imaging modalities that corroborate the biochemical and histologic findings to establish the definitive diagnosis. Unrecognized, misdiagnosed, or improperly treated disturbance of bone growth can result in permanent deformity usually associated with disability. 116 references.« less

Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Hydrochloride Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery

ClinicalTrials.gov

2018-06-20

Adult Fibrosarcoma; Alveolar Soft Part Sarcoma; Angiomatoid Fibrous Histiocytoma; Atypical Fibroxanthoma; Clear Cell Sarcoma of Soft Tissue; Epithelioid Malignant Peripheral Nerve Sheath Tumor; Epithelioid Sarcoma; Extraskeletal Myxoid Chondrosarcoma; Extraskeletal Osteosarcoma; Fibrohistiocytic Neoplasm; Glomus Tumor of the Skin; Inflammatory Myofibroblastic Tumor; Intimal Sarcoma; Leiomyosarcoma; Liposarcoma; Low Grade Fibromyxoid Sarcoma; Low Grade Myofibroblastic Sarcoma; Malignant Cutaneous Granular Cell Tumor; Malignant Peripheral Nerve Sheath Tumor; Malignant Triton Tumor; Mesenchymal Chondrosarcoma; Myxofibrosarcoma; Myxoid Chondrosarcoma; Myxoinflammatory Fibroblastic Sarcoma; Nerve Sheath Neoplasm; PEComa; Pericytic Neoplasm; Plexiform Fibrohistiocytic Tumor; Sclerosing Epithelioid Fibrosarcoma; Stage IB Soft Tissue Sarcoma AJCC v7; Stage IIB Soft Tissue Sarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Synovial Sarcoma; Undifferentiated (Embryonal) Sarcoma; Undifferentiated High Grade Pleomorphic Sarcoma of Bone

Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I.

PubMed

Pievani, Alice; Azario, Isabella; Antolini, Laura; Shimada, Tsutomu; Patel, Pravin; Remoli, Cristina; Rambaldi, Benedetta; Valsecchi, Maria Grazia; Riminucci, Mara; Biondi, Andrea; Tomatsu, Shunji; Serafini, Marta

2015-03-05

Neonatal bone marrow transplantation (BMT) could offer a novel therapeutic opportunity for genetic disorders by providing sustainable levels of the missing protein at birth, thus preventing tissue damage. We tested this concept in mucopolysaccharidosis type I (MPS IH; Hurler syndrome), a lysosomal storage disorder caused by deficiency of α-l-iduronidase. MPS IH is characterized by a broad spectrum of clinical manifestations, including severe progressive skeletal abnormalities. Although BMT increases the life span of patients with MPS IH, musculoskeletal manifestations are only minimally responsive if the timing of BMT delays, suggesting already irreversible bone damage. In this study, we tested the hypothesis that transplanting normal BM into newborn MPS I mice soon after birth can prevent skeletal dysplasia. We observed that neonatal BMT was effective at restoring α-l-iduronidase activity and clearing elevated glycosaminoglycans in blood and multiple organs. At 37 weeks of age, we observed an almost complete normalization of all bone tissue parameters, using radiographic, microcomputed tomography, biochemical, and histological analyses. Overall, the magnitude of improvements correlated with the extent of hematopoietic engraftment. We conclude that BMT at a very early stage in life markedly reduces signs and symptoms of MPS I before they appear. © 2015 by The American Society of Hematology.

A Unique Triad: Ulcerative Colitis, Primary Sclerosing Cholangitis, and Autoimmune Hemolytic Anemia.

PubMed

Naqvi, Syeda; Hasan, Syed Askari; Khalid, Sameen; Abbass, Aamer; Albors-Mora, Melanie

2018-01-15

Ulcerative colitis is an autoimmune disorder leading to chronic intestinal inflammation. It can present with a wide range of associated extra-intestinal manifestations. We present a case of an 18-year-old man diagnosed with ulcerative colitis, autoimmune hemolytic anemia and primary sclerosing cholangitis during the same hospitalization. The unique triad of these diseases gives important clues to the immunological factors involved in the pathogenesis of these diseases.

Atypical subacute sclerosing panencephalitis with short onset latency.

PubMed

Saurabh, Kumar; Gupta, Ratan; Khare, Shashi; Sharma, Shobha

2013-02-01

An 11-month-old boy presented with focal seizures, myoclonic jerks and altered sensorium of one month duration, with a history of measles at eight months of age. A diagnosis of Subacute sclerosing panencephalitis (SSPE) was made on the basis of typical EEG changes and presence of anti-measles antibody in cerebrospinal fluid. A differential diagnosis of SSPE should be considered in all forms of acute encephalopathy in infants for early diagnosis and management.

Subacute sclerosing panencephalitis presenting as mania

PubMed Central

Aggarwal, Ashish; Khandelwal, Ashish; Jain, Manish; Jiloha, R. C.

2011-01-01

Subacute sclerosing panencephalitis (SSPE) is a rare, invariably fatal degenerative disease of the central nervous system developing after measles infection. Besides neurological symptoms as initial presenting symptoms, rare reports of its presentation with pure psychiatric symptoms have been reported. We here report a case of 14 year old male who initially presented with manic symptoms and then subsequently diagnosed to be suffering from SSPE. Improtance of ruling our organic conditions is emphasized. PMID:21808475

Lateral patellar dislocation: mechanism of disease, radiographic presentation, and management.

PubMed

Abramov, Michael; Stock, Harlan

2013-04-01

Lateral patellar dislocation is a common injury occurring in young active adults. The mechanism is that of twisting injury to the knee on a planted foot with valgus stress. Several predisposing factors, including femoral trochlear dysplasia, patella alta, and lateralization of the tibial tuberosity, contribute to patellar instability and lateral patellar dislocation. Magnetic resonance (MR) imaging of the knee is the modality of choice to evaluate underlying bone contusion patterns, associated soft-tissue injuries, and additional complex ligamentous and osteochondral injuries, many of which are not apparent on conventional radiographs.

Imaging spectrum of cholangiocarcinoma: role in diagnosis, staging, and posttreatment evaluation.

PubMed

Mar, Winnie A; Shon, Andrew M; Lu, Yang; Yu, Jonathan H; Berggruen, Senta M; Guzman, Grace; Ray, Charles E; Miller, Frank

2016-03-01

Cholangiocarcinoma, a tumor of biliary epithelium, is increasing in incidence. The imaging appearance, behavior, and treatment of cholangiocarcinoma differ according to its location and morphology. Cholangiocarcinoma is usually classified as intrahepatic, perihilar, or distal. The three morphologies are mass-forming, periductal sclerosing, and intraductal growing. As surgical resection is the only cure, prompt diagnosis and accurate staging is crucial. In staging, vascular involvement, longitudinal spread, and lymphadenopathy are important to assess. The role of liver transplantation for unresectable peripheral cholangiocarcinoma will be discussed. Locoregional therapy can extend survival for those with unresectable intrahepatic tumors. The main risk factors predisposing to cholangiocarcinoma are parasitic infections, primary sclerosing cholangitis, choledochal cysts, and viral hepatitis. Several inflammatory conditions can mimic cholangiocarcinoma, including IgG4 disease, sclerosing cholangitis, Mirizzi's syndrome, and recurrent pyogenic cholangitis. The role of PET in diagnosis and staging will also be discussed. Radiologists play a crucial role in diagnosis, staging, and treatment of this disease.

European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes.

PubMed

Knobler, R; Moinzadeh, P; Hunzelmann, N; Kreuter, A; Cozzio, A; Mouthon, L; Cutolo, M; Rongioletti, F; Denton, C P; Rudnicka, L; Frasin, L A; Smith, V; Gabrielli, A; Aberer, E; Bagot, M; Bali, G; Bouaziz, J; Braae Olesen, A; Foeldvari, I; Frances, C; Jalili, A; Just, U; Kähäri, V; Kárpáti, S; Kofoed, K; Krasowska, D; Olszewska, M; Orteu, C; Panelius, J; Parodi, A; Petit, A; Quaglino, P; Ranki, A; Sanchez Schmidt, J M; Seneschal, J; Skrok, A; Sticherling, M; Sunderkötter, C; Taieb, A; Tanew, A; Wolf, P; Worm, M; Wutte, N J; Krieg, T

2017-09-01

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum. © 2017 European Academy of Dermatology and Venereology.

Sclerotherapy for congenital lesions in the head and neck.

PubMed

Kim, Kwang Hyun; Sung, Myung-Whun; Roh, Jong-Lyel; Han, Moon Hee

2004-09-01

This study retrospectively reviews the results of sclerotherapy using several sclerosants for congenital lesions of the head and neck. Between May 1990 and May 2002, patients with lymphatic malformations were treated by sclerotherapy; 10 with bleomycin, and 25 with OK-432. OK-432 sclerotherapy was also applied in 9 patients with plunging ranula and in 1 patient with branchial anomaly. Percutaneous sclerotherapy with ethanolamine oleate was used in 29 patients with venous malformations, and 28 patients with pyriform sinus fistula were treated by trichloroacetic acid chemocauterization. Overall, two thirds of patients with these lesions showed marked to complete response. One case of mortality occurred in the bleomycin sclerotherapy group. However, no major complications by other sclerosants were found. In lymphatic malformations, history of excision before sclerotherapy was a poor prognostic factor. Sclerotherapy using these sclerosants is a safe and effective primary treatment for congenital lesions in the head and neck.

Oxidant and antioxidant status in children with subacute sclerosing panencephalitis.

PubMed

Caksen, Hüseyin; Ozkan, Mustafa; Cemek, Mustafa; Cemek, Fatma

2014-11-01

We analyzed serum alpha-tocopherol, beta-carotene, retinol, and ascorbic acid levels and malondialdehyde and reduced glutathione concentrations on erythrocyte and cerebrospinal fluid in 30 patients with subacute sclerosing panencephalitis to evaluate oxidant and antioxidant status. Serum alpha-tocopherol, beta-carotene, retinol, ascorbic acid levels, and erythrocyte and cerebrospinal fluid reduced glutathione concentrations were decreased; however, erythrocyte and cerebrospinal fluid malondialdehyde levels were increased in the patients. Cerebrospinal fluid malondialdehyde levels were different between clinical stages of the disease (P < .05). Higher cerebrospinal fluid malondialdehyde level was associated with the more severe clinical stage. A positive correlation was found between cerebrospinal fluid malondialdehyde level and clinical stages (r = 0.42; P < .05) and between erythrocyte malondialdehyde level and clinical stages (r = 0.40; P < .05). Our findings showed presence of oxidative damage in subacute sclerosing panencephalitis and that antioxidants were increased as defense mechanisms of the organism against oxidative damage. © The Author(s) 2013.

Measles virus–specific plasma cells are prominent in subacute sclerosing panencephalitis CSF

PubMed Central

Owens, G.P.; Ritchie, A.M.; Gilden, D.H.; Burgoon, M.P.; Becker, D.; Bennett, J.L.

2012-01-01

Objective To demonstrate the specificity of expanded CD138+ plasma cell clones recovered from the CSF of a patient with subacute sclerosing panencephalitis (SSPE) for measles virus (MV). Methods IgG variable region sequences of single-antibody-secreting CD138+ cells sorted from SSPE CSF were amplified by single-cell PCR and analyzed. Human IgG1 recombinant antibodies (rAbs) were produced from four expanded CD138+ clones and assayed for immunoreactivity against MV proteins. Results Clonal expansion was a prominent feature of the SSPE plasma cell repertoire, and each of the four rAbs assayed was specific for either the MV fusion or the MV nucleocapsid protein. Conclusions Expanded plasma cell clones in the CSF of patients with subacute sclerosing panencephalitis produce disease-relevant antibodies. Recombinant antibodies derived from CSF B cells could provide a tool to identify target antigens in idiopathic inflammatory disorders. PMID:17515543

Measles-vaccinated Israeli boy with subacute sclerosing panencephalitis.

PubMed

Har-Even, Ronly; Aichenbaum, Sergio; Rabey, Jose M; Livne, Amir; Bistritzer, Tzvy

2011-06-01

Subacute sclerosing panencephalitis is a rare neurologic disorder of childhood and adolescence. We describe a 16-year-old boy who manifested the disease despite proper vaccinations. He was hospitalized because of bedwetting, involuntary limb movements, abnormal speech, and balance disturbances. Immunoglobulin G antibodies against measles were strongly positive, with a high relative cerebrospinal fluid/serum ratio. Polymerase chain reaction for measles produced negative results. Electroencephalography registered slow activity with high voltage discharges every few seconds, and with triphasic complex morphology. Magnetic resonance imaging revealed diffuse white matter changes, mostly around the posterior regions and lateral ventricles. Treatment with valproic acid, levetiracetam, carbamazepine, and intravenous immunoglobulin G was ineffective. Inosiplex and interferon-β-1a were also administrated. The patient became comatose, with generalized myoclonic jerks, and died 1 year later. An autopsy was not performed. This patient illustrates that subacute sclerosing panencephalitis should be suspected among young vaccinated subjects. Copyright © 2011 Elsevier Inc. All rights reserved.

Function and regulation of primary cilia and intraflagellar transport proteins in the skeleton.

PubMed

Yuan, Xue; Serra, Rosa A; Yang, Shuying

2015-01-01

Primary cilia are microtubule-based organelles that project from the cell surface to enable transduction of various developmental signaling pathways. The process of intraflagellar transport (IFT) is crucial for the building and maintenance of primary cilia. Ciliary dysfunction has been found in a range of disorders called ciliopathies, some of which display severe skeletal dysplasias. In recent years, interest has grown in uncovering the function of primary cilia/IFT proteins in bone development, mechanotransduction, and cellular regulation. We summarize recent advances in understanding the function of cilia and IFT proteins in the regulation of cell differentiation in osteoblasts, osteocytes, chondrocytes, and mesenchymal stem cells (MSCs). We also discuss the mechanosensory function of cilia and IFT proteins in bone cells, cilia orientation, and other functions of cilia in chondrocytes. © 2014 New York Academy of Sciences.

Peripheral Cemento-Ossifying Fibroma: Case Series Literature Review

PubMed Central

Ganji, Kiran Kumar; Chakki, ArunKumar Bhimashankar; Nagaral, Sharanbasappa Chandrashekar; Verma, Esha

2013-01-01

The concept of fibroosseous lesions of bone has evolved over the last several decades and now includes two major entities: fibrous dysplasia and ossifying fibroma. Peripheral cemento-ossifying fibroma is a relatively rare tumour classified between fibroosseous lesions. It predominantly affects adolescents and young adults, with peak prevalence between 10 and 19 yrs. The cemento-ossifying fibroma is a central neoplasm of bone as well as periodontium which has caused considerable controversy because of confusion regarding terminology and the criteria for its diagnosis. The cemento-ossifying fibroma is odontogenic in origin, whereas ossifying fibroma is of bony origin. Lesions histologically similar to peripheral ossifying fibroma have been given various names in existing literature. Therefore, we present and discuss in this paper a series of cases of peripheral cemento-ossifying fibroma emphasizing the differential diagnosis. PMID:23365762

The evaluation of lumbosacral dysplasia in young patients with lumbosacral spondylolisthesis: comparison with controls and relationship with the severity of slip.

PubMed

Pawar, Abhijit; Labelle, Hubert; Mac-Thiong, Jean-Marc

2012-11-01

Comparison of lumbosacral dysplasia between normal individuals and patients with low and high grade spondylolisthesis has not been done previously. The objective of this study is to evaluate the relationship between lumbosacral dysplasia and severity of slip in young patients with lumbosacral spondylolisthesis. Postero-anterior and lateral radiographs of 120 normal individuals and 131 patients with developmental spondylolisthesis (91 low and 40 high grades) were reviewed. Quantitative evaluation of lumbosacral dysplasia was done using 6 criteria involving the degree of laminar dysplasia, degree of facet dysplasia, size of L5 transverse processes, L5/S1 disc height, type of sacral doming and L5 lumbar index. Subjects were categorized as having no/low, moderate or severe dysplasia based on the total dysplasia score. Comparisons in total dysplasia score between normal, low grade and high grade groups were performed and the correlation between degree of dysplasia and percentage of slip was assessed. Most normal individuals (88.3%) had no/low dysplasia; most patients with low grade spondylolisthesis (61.5%) had moderate dysplasia, while most patients with high grade spondylolisthesis (72.5%) had severe dysplasia. There was a significant difference in dysplasia between normal individuals and patients with spondylolisthesis. Dysplasia also varied significantly between low and high grade spondylolisthesis. There was a strong positive correlation (r = 0.63) between severity of dysplasia and percentage of slip. There is a significant relationship between the severity of spondylolisthesis and lumbosacral dysplasia, with mainly no/low dysplasia observed in controls and increasing total dysplasia scores in higher grades of spondylolisthesis. In addition, a variable degree of dysplasia was found within groups with low or high grade spondylolisthesis, suggesting that different subgroups of patients exist with regard to dysplasia. Thus the degree of dysplasia varies in spondylolisthesis and it is possible that different grades of dysplasia could relate to different prognoses or outcomes with treatment.

Growth hormone-Insulin-like growth factor 1 axis hyperactivity on bone fibrous dysplasia in McCune-Albright Syndrome.

PubMed

Tessaris, Daniele; Boyce, Alison M; Zacharin, Margaret; Matarazzo, Patrizia; Lala, Roberto; De Sanctis, Luisa; Collins, Michael T

2018-04-19

In fibrous dysplasia (BFD), normal bone and bone marrow are replaced by fibro-osseous tissue, leading to fracture, deformity and pain. BFD may be isolated, or in association with cutaneous hyperpigmentation and/or hyperfunctioning endocrinopathies, termed McCune-Albright syndrome (MAS). GH hypersecretion has been described in 10%-20% of MAS-BFD patients. Aim of the study was to determine the impact of GH-insulin like growth factor 1 (IGF1) axis hyperactivity on MAS-BFD morbidities and the efficacy of GH excess therapy. A multicentric cross-sectional analysis was conducted on three different MAS cohorts. From 195 MAS patients, 37 subjects (19%) with GH excess were identified and compared with 34 MAS controls without GH hypersecretion. Mean head circumference SDS was significantly higher in GH excess: 4.025 SDS vs 0.683 SDS (P < .0001). The risk of optic neuropathy (Odds ratio 4.231; P = .039), hearing deficit (Odds ratio 2.961; P = .0481), facial asymmetry (Odds ratio 6.563; P = .0192), malignancies (Odds ratio 15.24; P = .0173) were higher in GH excess group. Overall, pharmacotherapy (octreotide alone 10-30 mg/mo or with pegvisomant 10-20 mg/d) was effective in IGF1 normalization (IGF1 Z-score between -2 and +2 SDS) in 21/29 patients (72.4%) with good compliance to the regimen. Late diagnosis and GH excess treatment after 16 years old of age was associated with an increased risk of optic neuropathy (Odds ratio 4.500; P = .0491) and growth of pituitary adenomas (Odds ratio 7.846; P = .050). GH-IGF1 hyperactivity increases risk of morbidities in MAS. Medical therapy is effective in normalizing IGF1 in most patients, and early treatment during paediatric age is associated with a decreased risk of optic neuropathy and GH-secreting adenomas growth. © 2018 John Wiley & Sons Ltd.

Case report: severe melorheostosis involving the ipsilateral extremities.

PubMed

Long, Hai-Tao; Li, Kang-Hua; Zhu, Yong

2009-10-01

Melorheostosis is a rare, noninheritable bone dysplasia characterized by its classic radiographic feature of flowing hyperostosis resembling dripping candle wax, generally on one side of the long bone. The condition originally was described by Leri and Joanny in 1922. Its etiology remains speculative, and treatment in most instances has been symptomatic. Melorheostosis usually affects one limb, more often the lower extremity, and rarely the axial skeleton. We report a rare case of severe melorheostosis in the ipsilateral upper and lower extremities with normal contralateral extremities. The plain radiographs revealed almost all the bones in the affected extremities, from clavicle and scapula to distal phalanges of the fingers and from femur to distal phalanges of the toes, presented extensive, dense hyperostosis and heterotopic ossification in the periarticular soft tissue. Physical examination showed considerable swelling and deformities of the left limbs, stiffness and distortion of the joints, and anesthesia in the left ulnar regions of the forearm and hand. The examination of the right side was normal. Computed tomography scans showed multiple areas of classic candle wax-like hyperostosis and narrowing or disappearance of the medullary cavity. Histologic analysis confirmed the clinical and imaging diagnosis and revealed extremely dense sclerotic bone of cortical pattern.

Pleurodesis for malignant pleural effusions.

PubMed

Shaw, P; Agarwal, R

2004-01-01

Approximately half of all patients with metastatic cancer develop a malignant pleural effusion which is likely to lead to a significant reduction in quality of life secondary to symptoms such as dyspnoea and cough. The aim of pleurodesis in these patients is to prevent re-accumulation of the effusion and thereby of symptoms, and avoid the need for repeated hospitalization for thoracocentesis. Numerous clinical studies have been performed to try to determine the optimal pleurodesis strategy, and synthesis of the available evidence should facilitate this. The aims of this review were to ascertain the optimal technique of pleurodesis in cases of malignant pleural effusion; to confirm the need for a sclerosant; and to clarify which, if any, of the sclerosants is the most effective. The Cochrane Central Register of Controlled Trials was searched for studies on 'pleurodesis'. Studies for inclusion were also identified from MEDLINE (1980 to June 2002) and EMBASE (1980 to May 2002). No language restriction was applied. RCTs of adults subjects undergoing pleurodesis for pleural effusion in the context of metastatic malignancy (or a malignant process leading to pleural effusion) were included. Two reviewers independently selected studies for inclusion in the review, and extracted data using a standard data collection form. Primary outcome measures sought were effectiveness of pleurodesis as defined by freedom from recurrence of effusions, and mortality after pleurodesis. Secondary outcomes were adverse events due to pleurodesis. Dichotomous data were meta-analysed using a fixed effect model and expressed as relative risk. The number-needed-to-treat (NNT) was calculated for pleurodesis efficacy. In addition, for adverse events, the overall percentage of patients across studies exhibiting a particular adverse effect such as fever, pain, or gastrointestinal symptoms was calculated. A total of 36 RCTs with 1499 subjects were eligible for meta-analysis. The use of sclerosants (mitozantrone, talc and tetracycline combined)compared with control (instillation of isotonic saline or equivalent pH isotonic saline or tube drainage alone) was associated with an increased efficacy of pleurodesis. The relative risk (RR) of non-recurrence of an effusion is 1.20 (95% CI 1.04 to 1.38) in favour of the use of sclerosants based on five studies with a total 228 subjects. Comparing different sclerosants, talc was found to be the most efficacious. The RR of effusion non-recurrence was 1.34 (95% CI 1.16 to 1.55) in favour of talc compared with bleomycin, tetracycline, mustine or tube drainage alone based on 10 studies comprising 308 subjects. This was not associated with increased mortality post pleurodesis. The RR of death was 1.19 (95% CI 0.08 to 1.77) for talc compared to bleomycin, tetracycline, mustine and tube drainage alone based on six studies of 186 subjects. Death was not reported in all studies and, when reported, was attributed to underlying disease, only one death being reported as procedure-related. In the comparison of thoracoscopic versus medical pleurodesis, thoracoscopic pleurodesis was found to be more effective. The RR of non-recurrence of effusion is 1.19 (95% CI 1.04 to 1.36) in favour of thoracoscopic pleurodesis compared with tube thoracostamy pleurodesis utilizing talc as sclerosant based on two studies with 112 subjects. Comparing thoracoscopic versus bedside instillation (with different sized chest tubes) of various sclerosants (tetracycline, bleomycin, talc or mustine) the RR of non-recurrence of effusion is 1.68 (95% CI 1.35 to 2.10) based on five studies with a total of 145 participants.Adverse events were not reported adequately to enable meta-analysis. The available evidence supports the need for chemical sclerosants for successful pleurodesis, the use of talc as the sclerosant of choice, and thoracoscopic pleurodesis as the preferred technique for pleurodesis based on efficacy. There was no evidence for an increase in mortality following talc pleurodesis.

Subacute sclerosing panencephalitis in immunized Thai children.

PubMed

Khusiwilai, Khanittha; Viravan, Sorawit

2011-12-01

Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disease with high mortality and poor prognosis. This is caused by persistent defective measles virus infection. Clinical presentations are variable including behavioral-cognitive change, myoclonic seizure, visual problem, spasticity or abnormal movement. The authors report a case of 10 year-old boy, previously healthy with complete immunization, presenting with frequent myoclonic jerks, abnormal movements, spasticity and altered mental status. Electroencephalographic (EEG), magnetic resonance imaging (MRI), and laboratory findings are typical for SSPE.

Subacute sclerosing panencephalitis presenting as acute cerebellar ataxia and brain stem hyperintensities.

PubMed

Saini, Arushi Gahlot; Sankhyan, Naveen; Padmanabh, Hansashree; Sahu, Jitendra Kumar; Vyas, Sameer; Singhi, Pratibha

2016-05-01

Subacute sclerosing panencephalitis is a devastating neurodegenerative disease with a characteristic clinical course. Atypical presentations may be seen in 10% of the cases. To describe the atypical clinical and radiological features of SSPE in a child form endemic country. A 5-year-old boy presented with acute-onset cerebellar ataxia without associated encephalopathy, focal motor deficits, seizures or cognitive decline. He had varicella-like illness with vesicular, itchy truncal rash erupting one month prior to the onset of these symptoms. He underwent detailed neurological assessment, relevant laboratory and radiological investigations. Neuroimaging revealed peculiar brain stem lesions involving the pons and cerebellum suggestive of demyelination. With a presumptive diagnosis of clinically isolated syndrome of demyelination, he was administered pulse methylprednisolone (30 mg/kg/day for 5 days). Four weeks later he developed myoclonic jerks. Electroencephalogram showed characteristic periodic complexes time-locked with myoclonus. CSF and serum anti-measles antibody titres were elevated (1:625). Our report highlights that subacute sclerosing panencephalitis can present atypically as isolated acute cerebellar ataxia and peculiar involvement of longitudinal and sparing of transverse pontine fibres. The predominant brainstem abnormalities in the clinical setting may mimick acute demyelinating syndrome. Hence, it is important to recognize these features of subacute sclerosing panencephalitis in children, especially in the endemic countries. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The features of mucosa-associated microbiota in primary sclerosing cholangitis.

PubMed

Torres, J; Bao, X; Goel, A; Colombel, J-F; Pekow, J; Jabri, B; Williams, K M; Castillo, A; Odin, J A; Meckel, K; Fasihuddin, F; Peter, I; Itzkowitz, S; Hu, J

2016-04-01

Little is known about the role of the microbiome in primary sclerosing cholangitis. To explore the mucosa-associated microbiota in primary sclerosing cholangitis (PSC) patients across different locations in the gut, and to compare it with inflammatory bowel disease (IBD)-only patients and healthy controls. Biopsies from the terminal ileum, right colon, and left colon were collected from patients and healthy controls undergoing colonoscopy. Microbiota profiling using bacterial 16S rRNA sequencing was performed on all biopsies. Forty-four patients were recruited: 20 with PSC (19 with PSC-IBD and one with PSC-only), 15 with IBD-only and nine healthy controls. The overall microbiome profile was similar throughout different locations in the gut. No differences in the global microbiome profile were found. However, we observed significant PSC-associated enrichment in Barnesiellaceae at the family level, and in Blautia and an unidentified Barnesiellaceae at the genus level. At the operational taxa unit level, most shifts in PSC were observed in Clostridiales and Bacteroidales orders, with approximately 86% of shifts occurring within the former order. The overall microbiota profile was similar across multiple locations in the gut from the same individual regardless of disease status. In this study, the mucosa associated-microbiota of patients with primary sclerosing cholangitis was characterised by enrichment of Blautia and Barnesiellaceae and by major shifts in operational taxa units within Clostridiales order. © 2016 John Wiley & Sons Ltd.

Kidney Dysplasia

MedlinePlus

... Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Dysplasia What is kidney dysplasia? Kidney dysplasia is a condition in which ... Kidney dysplasia in one kidney What are the kidneys and what do they do? The kidneys are ...

McCune Albright syndrome in association with excessive GH secretion: case report.

PubMed

Özsu, Elif; Mutlu, Gül Yeşiltepe; Çizmecioğlu, Filiz Mine; Hatun, Şükrü

2015-06-01

McCune-Albright Syndrome is a rare syndrome characterized with excessive function of peripheral endocrine organs and activating mutations of the stimulatory G protein alpha subunit are involved in the pathogenesis. The three main findings of the disease include hyperpigmented café au lait spots, fibrous dysplasia and increased endocrine functions and excessive secretion of growth hormone is observed in 21% of the patients. Clinical signs may be missed in these patients because of precocious puberty and craniofacial fibrous dysplasia. Since radiotherapy causes to sarcomatous changes and transsphenoidal surgery may cause to severe thickening in the cranial bones, they are not appropriate treatment options and medical treatment is recommended. Bromocriptine, cabergoline and octreotide or different combinations of these drugs are used in treatment and pegvisomant has also been used in recent years. Here, we present a male patient aged 12 years and 7 months to show gigantism as a rare clinical reflection of McCune-Albright Syndrome with an excessive height (197 cm), café au lait spots, growht hormone levels which could not be supressed with oral glucose tolerance test and increased prolactin levels.

Diagnosing and discriminating between primary and secondary aneurysmal bone cysts

PubMed Central

Sasaki, Hiromi; Nagano, Satoshi; Shimada, Hirofumi; Yokouchi, Masahiro; Setoguchi, Takao; Ishidou, Yasuhiro; Kunigou, Osamu; Maehara, Kosuke; Komiya, Setsuro

2017-01-01

Aneurysmal bone cysts (ABCs) are benign bony lesions frequently accompanied by multiple cystic lesions and aggressive bone destruction. They are relatively rare lesions, representing only 1% of bone tumors. The pathogenesis of ABCs has yet to be elucidated. In the present study, a series of 22 cases of primary and secondary ABC from patients treated in Department of Orthopedic Surgery, Kagoshima University Hospital (Kagoshima, Japan) from 2001–2015 were retrospectively analyzed. The average age at the time of diagnosis of primary ABC was 17.9 years. Intralesional curettage and artificial bone grafting were performed in the majority of the patients with primary ABC. The local recurrence rate following curettage for primary ABC was 18%, and the cause of local recurrence was considered to be insufficient curettage. Although no adjuvant therapy was administered during the surgeries, it may assist the prevention of local recurrence in certain cases. The cases of secondary ABC were preceded by benign bone tumors, including fibrous dysplasia, giant cell tumors, chondroblastoma and non-ossifying fibroma. The features of the secondary ABC typically reflected those of the preceding bone tumor. In the majority of cases, distinguishing the primary ABC from the secondary ABC was possible based on characteristic features, including age of the patient at diagnosis and the tumor location. In cases that exhibit ambiguous features, including a soft tissue mass or a thick septal enhancement on the preoperative magnetic resonance images, a biopsy must be obtained in order to exclude other types of aggressive bone tumors, including giant cell tumor, osteosarcoma and telangiectatic osteosarcoma. PMID:28454393

Hematopoietic stem cell transplantation for Morquio A syndrome.

PubMed

Yabe, Hiromasa; Tanaka, Akemi; Chinen, Yasutsugu; Kato, Shunichi; Sawamoto, Kazuki; Yasuda, Eriko; Shintaku, Haruo; Suzuki, Yasuyuki; Orii, Tadao; Tomatsu, Shunji

2016-02-01

Morquio A syndrome features systemic skeletal dysplasia. To date, there has been no curative therapy for this skeletal dysplasia. No systemic report on a long-term effect of hematopoietic stem cell transplantation (HSCT) for Morquio A has been described. We conducted HSCT for 4 cases with Morquio A (age at HSCT: 4-15years, mean 10.5years) and followed them at least 10years (range 11-28years; mean 19years). Current age ranged between 25 and 36years of age (mean 29.5years). All cases had a successful full engraftment of allogeneic bone marrow transplantation without serious GVHD. Transplanted bone marrow derived from HLA-identical siblings (three cases) or HLA-identical unrelated donor. The levels of the enzyme activity in the recipient's lymphocytes reached the levels of donors' enzyme activities within two years after HSCT. For the successive over 10years post-BMT, GALNS activity in lymphocytes was maintained at the same level as the donors. Except one case who had osteotomy in both legs one year later post BMT, other three cases had no orthopedic surgical intervention. All cases remained ambulatory, and three of them could walk over 400m. Activity of daily living (ADL) in patients with HSCT was better than untreated patients. The patient who underwent HSCT at four years of age showed the best ADL score. In conclusion, the long-term study of HSCT has demonstrated therapeutic effect in amelioration of progression of the disease in respiratory function, ADL, and biochemical findings, suggesting that HSCT is a therapeutic option for patients with Morquio A. Copyright © 2015 Elsevier Inc. All rights reserved.

Hematopoietic Stem Cell Transplantation for Morquio A Syndrome

PubMed Central

Yabe, Hiromasa; Tanaka, Akemi; Chinen, Yasutsugu; Kato, Shunichi; Sawamoto, Kazuki; Yasuda, Eriko; Shintaku, Haruo; Suzuki, Yasuyuki; Orii, Tadao; Tomatsu, Shunji

2016-01-01

Morquio A syndrome features systemic skeletal dysplasia. To date, there has been no curative therapy for this skeletal dysplasia. No systemic report on a long-term effect of hematopoietic stem cell transplantation (HSCT) for Morquio A has been described. We conducted HSCT for 4 cases with Morquio A (age at HSCT: 4–15 years, mean 10.5 years) and followed them at least 10 years (range 11–28 years; mean 19 years). Current age ranged between 25 and 36 years of age (mean 29.5 years). All cases had a successful full engraftment of allogeneic bone marrow transplantation without serious GVHD. Transplanted bone marrow derived from HLA-identical siblings (three cases) or HLA-identical unrelated donor. The levels of the enzyme activity in the recipient’s lymphocytes reached the levels of donors’ enzyme activities within two years after HSCT. For the successive over 10 years post-BMT, GALNS activity in lymphocytes was maintained at the same level as the donors. Except one case who had osteotomy in both legs one year later post BMT, other three cases had no orthopedic surgical intervention. All cases remained ambulatory, and three of them could walk over 400 m. Activity of daily living (ADL) in patients with HSCT was better than untreated patients. The patient who underwent HSCT at four years of age showed the best ADL score. In conclusion, the long-term study of HSCT has demonstrated therapeutic effect in amelioration of progression of the disease in respiratory function, ADL, and biochemical findings, suggesting that HSCT is a therapeutic option for patients with Morquio A. PMID:26452513

Present status and perspective of laboratory hematology in Japan: On the standardization of blood cell morphology including myelodysplasia: On behalf of the Japanese Society for Laboratory Hematology.

PubMed

Tohyama, K

2018-05-01

The Japanese Society for Laboratory Hematology (JSLH) was launched in 2000 and has been developed by a mutual collaboration of hematologists, medical technologists, and the companies involved in hematological laboratory testing. The aim of JSLH is the progress and development of laboratory hematology by academic conferences, periodic publication of academic journal, training and education (in the meeting, the journal, or the website), promotion of the standardization of laboratory hematology, and certification of the laboratory hematology specialists. Among 3 specialized committees organized for the standardization of laboratory hematology, the standardization committee on blood cell morphology has been dealing with the various projects on peripheral/bone marrow blood cells and normal/abnormal morphology. Another independent organization, the Japanese National Research Group on idiopathic bone marrow failure syndromes (BMF), has raised the importance of the dysplasia of myelodysplastic syndromes (MDS) and has been conducting the prospective registration, central review, and follow-up study of MDS. This group recently proposed the grading system for diagnostic accuracy of MDS, and the detailed procedure of morphological diagnosis of MDS is presented in the specialized color atlas with typical photographs of various dysplasia. JSLH has also approved the grading system for diagnostic accuracy of MDS and adopted this standardized diagnostic system to the educational item for certification of the laboratory hematology specialists, aiming at a nationwidely expanding morphological evaluation of myelodysplasia. Further and significant progress in the standardization of blood cell morphology will be expected in Japan through the activity of JSLH. © 2018 John Wiley & Sons Ltd.

Hearing loss and enlarged internal auditory canal in children.

PubMed

Santos, Saturnino; Domínguez, M Jesús; Cervera, Javier; Suárez, Alicia; Bueno, Antonio; Bartolomé, Margarita; López, Rafael

2014-01-01

Among the temporal bone abnormalities that can be found in the etiological study of paediatric sensorineural hearing loss (SNHL) by imaging techniques, those related to the internal auditory canal (IAC) are the least frequent. The most prevalent of these abnormalities that is associated with SNHL is stenotic IAC due to its association with cochlear nerve deficiencies. Less frequent and less concomitant with SNHL is the finding of an enlarged IAC (>8mm). Retrospective and descriptive review of clinical associations, imaging, audiological patterns and treatment of 9 children with hearing loss and enlarged IAC in the period 1999 to 2012. Two groups of patients are described. The first, without association with vestibulocochlear dysplasias, consisted of: 2 patients with SNHL without other temporal bone or systemic abnormalities, one with bilateral mixed HL from chromosome 18q deletion, one with a genetic X-linked DFN3 hearing loss, one with unilateral hearing loss in neurofibromatosis type 2 with bilateral acoustic neuroma, and one with unilateral hearing loss with cochlear nerve deficiency. The second group, with association with vestibulocochlear dysplasias, was comprised of: one patient with moderate bilateral mixed hearing loss in branchio-oto-renal syndrome, one with profound unilateral SNHL with recurrent meningitis, and another with profound bilateral SNHL with congenital hypothyroidism. The presence of an enlarged IAC in children can be found in different clinical and audiological settings with relevancies that can range from life-threatening situations, such as recurrent meningitis, to isolated hearing loss with no other associations. Copyright © 2013 Elsevier España, S.L. All rights reserved.

[McCune-Albright syndrome revealed by Blaschko-linear café-au-lait spots on the back].

PubMed

Jung, A-J; Soskin, S; Paris, F; Lipsker, D

2016-01-01

McCune-Albright syndrome is a rare sporadic disease defined by the triad of café-au-lait spots, fibrous dysplasia of bone and endocrine disorder. Diagnosis is classically confirmed by the presence of bone lesions or precocious puberty. We report a case of McCune-Albright syndrome diagnosed solely on the basis of the cutaneous signs. A four-year-old girl was seen in our clinic due to the presence of congenital café-au-lait spots on her back. These macules were irregular, with jagged borders, and were disposed in a broad band on the left shoulder and in the lumbar region, in a Blaschko-linear pattern. McCune-Albright syndrome was immediately suspected, despite the absence of other signs of the disease. Genetic assessment carried out a year and a half later confirmed the diagnosis, with arginine substitution at position 201 of Gs alpha protein. The child was still asymptomatic. Regular radiographic and endocrine assessments remained normal for three years until the sudden appearance at the age of seven years of precocious puberty and radiographic evidence of fibrous dysplasia of the right hand. Café-au-lait spots are very common in the general population. An underlying genetic disorder should only be sought when such spots are multiple. However, in the case of McCune-Albright syndrome, it is the irregular borders and the Blaschko-linear arrangement of the spots in broad irregular bands that are pathognomonic, reflecting as they do the genetic mosaicism characteristic of this disease. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The effect of neonatal gene therapy on skeletal manifestations in mucopolysaccharidosis VII dogs after a decade.

PubMed

Xing, Elizabeth M; Knox, Van W; O'Donnell, Patricia A; Sikura, Tracey; Liu, Yuli; Wu, Susan; Casal, Margret L; Haskins, Mark E; Ponder, Katherine P

2013-06-01

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disease due to deficient activity of β-glucuronidase (GUSB), and results in glycosaminoglycan accumulation. Skeletal manifestations include bone dysplasia, degenerative joint disease, and growth retardation. One gene therapy approach for MPS VII involves neonatal intravenous injection of a gamma retroviral vector expressing GUSB, which results in stable expression in liver and secretion of enzyme into blood at levels predicted to be similar or higher to enzyme replacement therapy. The goal of this study was to evaluate the long-term effect of neonatal gene therapy on skeletal manifestations in MPS VII dogs. Treated MPS VII dogs could walk throughout their lives, while untreated MPS VII dogs could not stand beyond 6 months and were dead by 2 years. Luxation of the coxofemoral joint and the patella, dysplasia of the acetabulum and supracondylar ridge, deep erosions of the distal femur, and synovial hyperplasia were reduced, and the quality of articular bone was improved in treated dogs at 6 to 11 years of age compared with untreated MPS VII dogs at 2 years or less. However, treated dogs continued to have osteophyte formation, cartilage abnormalities, and an abnormal gait. Enzyme activity was found near synovial blood vessels, and there was 2% as much GUSB activity in synovial fluid as in serum. We conclude that neonatal gene therapy reduces skeletal abnormalities in MPS VII dogs, but clinically-relevant abnormalities remain. Enzyme replacement therapy will probably have similar limitations long-term. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparative trial of sclerotherapy for hydroceles.

PubMed

Rencken, R K; Bornman, M S; Reif, S; Olivier, I

1990-04-01

We present a prospective single-blind trial of sclerotherapy for hydroceles with tetradecyl sulphate and rolitetracycline as sclerosants. Twenty-seven hydroceles were treated with tetradecyl sulphate and 28 with rolitetracycline. The median follow-up was 13 months. There were no statistically significant differences between the 2 drugs in respect of cure rate and complications. The overall cure rate for both drugs was 96%. Complications were rare and common to both drugs. Tetradecyl sulphate and rolitetracycline were found to be equally effective as sclerosants.

[Acquired hydrocele in the adult: sclerotherapy].

PubMed

Castillo Jimeno, J M; González de Garibay, A S; Sebastían Borruel, J L; Valdivia Uría, J G

1991-06-01

We report our experience in the treatment of hydrocele using sclerosant therapy in 50 patients with adult acquired hydrocele (AAH) or cord cyst (CC). The sclerosing agent utilized in all of the patients was quinacrine dihydrochloride (quinacrine) at a dose of 13.3 mg 50 cc aspirated volume. The results were assessed clinically, ultrasonographically and thermographically. The presence of multilocular cysts or incomplete aspiration of the liquid was the most frequent cause of failure. The results show a success rate of 85%; however, 18% required more than one treatment.

An 111In-Pentetreotide Positive Sclerosing Pneumocytoma.

PubMed

Savelli, Giordano; Bnà, Claudio; Zambelli, Claudia; Illuminati, Sonia; Bonello, Luke

2017-04-01

A 43-year-old woman had an incidental lung mass identified on shoulder x-ray performed for pain. Contrast-enhanced CT showed a 38-mm mass in the medial segment of the right middle lobe, with features suggestive of carcinoid tumor. A In-pentetreotide scan showed intense uptake; furthermore, fine needle aspiration biopsy yielded neuroendocrine cells confirming the carcinoid hypothesis. However, definitive surgical histology showed a sclerosing pneumocytoma. This could potentially suggest that such rare tumors, with metastatic potential, could respond to somatostatin analogue treatment.

Subacute sclerosing panencephalitis. Changes on CT scan during acute relapse.

PubMed

Modi, G; Campbell, H; Bill, P

1989-01-01

A 19-year-old female patient presented in an acute state of akinetic mutism. Serological analysis of serum and cerebrospinal fluid demonstrated the presence of antibodies to measles virus. CT scan carried out during this acute phase of relapse demonstrated white matter enhancement affecting the cortical white matter of the frontal lobes and corpus callosum. These features indicate that active demyelination occurs during acute relapse in subacute sclerosing panencephalitis (SSPE) and suggest that immunotherapy should be considered during this acute phase.

Wild-type Measles Virus in Brain Tissue of Children with Subacute Sclerosing Panencephalitis, Argentina

PubMed Central

Barrero, Paola Roxana; Grippo, Jorge; Viegas, Mariana

2003-01-01

We studied eight children who had measles at 6 to 10 months of age during the 1998 Argentine measles outbreak and in whom subacute sclerosing panencephalitis developed 4 years later. We report the genetic characterization of brain tissue–associated measles virus samples from three patients. Phylogenetic relationships clustered these viruses with the wild-type D6 genotype isolated during the 1998 outbreak. The children received measles vaccine; however, vaccinal strains were not found. PMID:14609476

MRI and MR spectroscopy findings of a case of subacute sclerosing panencephalitis affecting the corpus callosum

PubMed Central

Öztürk, Mehmet; Sığırcı, Ahmet; Yakıncı, Cengiz

2015-01-01

Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressive, fatal, inflammatory and neurodegenerative disease that is seen mostly in children and young adolescents, and primarily affects the parieto-occipital lobes. The corpus callosum, cerebellum and basal ganglia are less frequently involved. MR spectroscopy (MRS) may illustrate the pathophysiological features of SSPE. To the best of our knowledge, this is the second report of MRS findings of corpus callosum involvement in a stage 3 SSPE case. PMID:26163552

Left spermatic vein retrograde sclerosis: comparison between sclerosant agent injection through a diagnostic catheter versus through an occluding balloon catheter.

PubMed

Basile, Antonio; Failla, Giovanni; La Vignera, Sandro; Condorelli, Rosita Angela; Calogero, Aldo; Vicari, Enzo; Granata, Antonio; Mundo, Elena; Caltabiano, Giuseppe; Pizzarelli, Marco; Messina, Martina; Scavone, Giovanni; Lanzafame, Franz; Iezzi, Roberto; Tsetis, Dimitrios

2015-05-01

The aim of this study was to compare the technical success between left spermatic vein (LSV) scleroembolisation achieved with the injection of sclerosant through a diagnostic catheter and through an occluding balloon (OB), in the treatment of male varicocele. From January 2012 to September 2013, we prospectively enrolled 100 patients with left varicocele and an indication for LSV scleroembolisation related to symptoms or spermiogram anomalies; patients were randomised to two groups (we wrote a list of 100 lines assigned casually with A or B and each patient was consecutively allocated to group A or B on the basis of this list). Patients in group A underwent injection of the sclerosing agent through an angiographic diagnostic catheter (free catheter technique) and patients in group B through an OB catheter (OB technique). In cases of incomplete occlusion of the LSV, the procedure was completed with coils. Total occlusion of the LSV at post-treatment phlebography during a Valsalva manoeuvre before any coil embolisation was considered a technical success. The rate of complications was also evaluated. The Fischer's test was used for statistical analysis. We evaluated a total of 90 patients because five patients for each group were not included in the statistical analysis owing to technical problems or complications. In group A we had a technical success of 75.6 versus 93.4 % in group B, and the difference was statistically significant (P = 0.003); in particular, we had to complete the embolisation with insertion of coils in 11 cases (24.4 %) in group A, and in three cases in group B (6.6 %). In group A, LSV rupture occurred in four cases (8 %) so the procedure was completed by sclerosant injection through the OB located distally to the lesion. These patients were not considered for evaluation. In another case, a high flow shunt towards the inferior vena cava was detected, so the patient underwent OB injection to stop the flow to the shunt, and was not included for statistical evaluation. In group B, vein rupture with contrast leakage was noted in six cases (12 %); nonetheless, all the procedures were completed because the OB was positioned distally to the vessel tear, obviating any retrograde leakage of sclerosant. In group B, in five cases (10 %), we were unable to advance the OB though the LSV ostium so the procedures were completed with the diagnostic catheter and not considered for statistical evaluation. On the basis of our data, the embolisation of the LSV obtained by injecting the sclerosant through an OB rather than through a diagnostic catheter seems to be more effective in achieving total vein embolisation, as well as allowing a controlled injection of sclerosant even in cases of vein rupture.

Osteogenesis imperfecta.

PubMed

Forlino, Antonella; Marini, Joan C

2016-04-16

Osteogenesis imperfecta is a phenotypically and molecularly heterogeneous group of inherited connective tissue disorders that share similar skeletal abnormalities causing bone fragility and deformity. Previously, the disorder was thought to be an autosomal dominant bone dysplasia caused by defects in type I collagen, but in the past 10 years discoveries of novel (mainly recessive) causative genes have lent support to a predominantly collagen-related pathophysiology and have contributed to an improved understanding of normal bone development. Defects in proteins with very different functions, ranging from structural to enzymatic and from intracellular transport to chaperones, have been described in patients with osteogenesis imperfecta. Knowledge of the specific molecular basis of each form of the disorder will advance clinical diagnosis and potentially stimulate targeted therapeutic approaches. In this Seminar, together with diagnosis, management, and treatment, we describe the defects causing osteogenesis imperfecta and their mechanism and interrelations, and classify them into five groups on the basis of the metabolic pathway compromised, specifically those related to collagen synthesis, structure, and processing; post-translational modification; folding and cross-linking; mineralisation; and osteoblast differentiation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification

PubMed Central

Regard, Jean B.; Malhotra, Deepti; Gvozdenovic-Jeremic, Jelena; Josey, Michelle; Chen, Min; Weinstein, Lee S.; Lu, Jianming; Shore, Eileen M.; Kaplan, Frederick S.; Yang, Yingzi

2014-01-01

Bone formation is exquisitely controlled in space and time. Heterotopic ossification (HO), the pathologic formation of extra-skeletal bone, occurs as a common complication of trauma or in genetic disorders and can be disabling and lethal. However, the underlying molecular mechanisms are largely unknown. Here we demonstrate that Gαs restricts bone formation to the skeleton by inhibiting Hedgehog (Hh) signaling in mesenchymal progenitor cells. In progressive osseous heteroplasia (POH), a human disease caused by null mutations in GNAS that encodes Gαs, HH signaling is upregulated in ectopic osteoblasts and progenitor cells. Ectopic Hh signaling is sufficient to induce HO, while Hh signaling inhibition blocks HO in animal models. As our previous work has shown that GNAS gain of function mutations upregulate WNT/β-Catenin signaling in fibrous dysplasia (FD), our findings identify Gαs as a critical regulator of osteoblast differentiation by maintaining a balance between two key signaling pathways: Wnt/β-catenin and Hh. HH signaling inhibitors developed for cancer therapy may be repurposed to treat HO and other diseases caused by GNAS inactivation. PMID:24076664

CD4+ acute undifferentiated leukaemia, probably early monoblastic type, developing in a patient with myelodysplastic syndrome and bone marrow fibrosis.

PubMed

Guenova, M; Taskov, H; Zechev, J

1997-07-01

We report here a patient who presented with pancytopenia, hypercellular bone marrow and three-lineage dysplasia associated with an increase of reticulin fibres. After a 5-month period, anaemia and thrombocytopenia progressed very rapidly and the white blood count increased showing 45% blasts with monocytoid morphology, but cytochemically undifferentiated in nature. The immunophenotype revealed an unusual expression of CD4, CD36 and HLA-DR in the absence of any other myeloid or lymphoid lineage-associated markers. The patient died unexpectedly during the course of chemotherapy. The occurrence of CD4, CD36 and HLA-DR on the blast cells cannot determine the lineage of differentiation with certainty but provides some evidence that the leukaemic cells were probably derived from a very early monocytic progenitor with maturation arrest. These cells had apparently complex interactions with pathologic megakaryocytes and cytokine production.

Trust in the patient’s history: cough and eels

PubMed Central

Mackay, Alexander John; Burke, Stephen; Bothamley, Graham

2009-01-01

A 54-year-old ex-smoker was referred to the respiratory clinic for breathlessness and wheeze. His symptoms started while eating jellied eels when he felt something stick in his throat. The following day, his general practitioner heard a wheeze in his right lower chest. A chest radiograph noted no foreign body. A course of antibiotics did not help, but steroids were beneficial. On clinic review the examination was normal apart from enlarged and inflamed tonsils. Fibreoptic bronchoscopy revealed a suspicious looking mass lesion completely occluding the bronchus intermedius. Biopsies of the lesion revealed inflamed bronchial mucosa and a fragment of bone. There was no evidence of dysplasia or malignancy. A computed tomography scan of the thorax revealed a 5 mm endobronchial soft tissue density with areas of calcification within the bronchus intermedius. At rigid bronchoscopy a spiny bone was removed and subsequently the patient’s shortness of breath, cough and wheeze improved. PMID:22110553

Oncogenic osteomalacia: a clinicopathologic study of 17 bone lesions.

PubMed Central

Park, Y. K.; Unni, K. K.; Beabout, J. W.; Hodgson, S. F.

1994-01-01

Oncogenic osteomalacia is an unusual and rare clinicopathologic syndrome characterized by mesenchymal tumors that apparently produce osteomalacia and biochemical abnormalities consisting of hypophosphatemia, normocalcemia, and increased levels of alkaline phosphatase. We collected from the Mayo Clinic files and from our consultation files the records for 17 cases of osteomalacia associated with bone lesions. There were five cases of fibrous dysplasia, three of hemangiopericytoma, and two of phosphaturic mesenchymal tumor. There was one case each of osteosarcoma, chondroblastoma, chondromyxoid fibroma, malignant fibrous histiocytoma, giant cell tumor, metaphyseal fibrous defect, and hemangioma. In this study we can figure out that the most common characteristic histologic features of our cases were hemangiopericytomatous vascular proliferation, fine lace-like stromal calcification, and stromal giant cells. In most of the cases, the clinical and biochemical symptoms and signs resolved soon after complete resection of the lesion. When the lesion recurred or metastasized, the symptoms and signs also recurred. PMID:7848576

Familial ectodermal dysplasia: a peers' agony.

PubMed

Hegde, Karthik; Kashyap, Roopashri Rajesh; Nair, Gopakumar; Nair, Preeti P

2013-07-23

Ectodermal dysplasias include a various group of inherited disorders which share primary defect in the development of two or more tissues of embryonic ectodermal origin. Though there are many subtypes, ectodermal dysplasias are mainly hidrotic ectodermal dysplasia and hypohidrotic ectodermal dysplasia, among which the most common variety is X linked hypohidrotic ectodermal dysplasia. We report a rare case of X linked hypohidrotic ectodermal dysplasia occurring in a family with various skin, hair and oral abnormalities.

Melorheostosis and FGF-23: is there a relationship?

PubMed

Kerkeni, Samar; Chapurlat, Roland

2008-07-01

Melorheostosis is a rare chronic bone disease of unknown etiology that often affects lower limbs. Onset usually occurs in childhood or early adolescence. The diagnosis relies on the radiographic finding of hyperostosis within or around the cortex responsible for a "flowing wax" appearance. To our knowledge, Fibroblast growth factor-23 (FGF-23) levels have not yet been quantified in melorheostosis. We report an unusual case of this disease for whom the diagnosis of fibrous dysplasia had been wrongly made for a long period of time and the FGF-23 concentration has been found very high without any disturbance of serum phosphate.

Kenny-Caffey Syndrome: oral findings and 4-year follow-up of overlay denture therapy.

PubMed

Demir, Tahsin; Kecik, Defne; Cehreli, Zafer C

2007-01-01

Kenny-Caffey Syndrome (KCS) is an extremely rare osteosclerotic bone dysplasia associated with hypocalcemia and ocular abnormalities. Although the condition is well reported in the medical literature, dental manifestations have not been discussed in great detail. The purpose of this report is to present specific oral features and prosthetic management in a KCS patient. Overlay dentures were utilized in the management of low vertical dimension of occlusion, congenital absence of several permanent teeth, and problems associated with function and esthetics. Results of the 4-year follow-up overlay denture therapy are presented.

Controversies in the definition and treatment of idiopathic short stature (ISS).

PubMed

Pedicelli, Stefania; Peschiaroli, Emanuela; Violi, Enrica; Cianfarani, Stefano

2009-01-01

The term idiopathic short stature (ISS) refers to short children with no identifiable disorder of the growth hormone (GH)/insulin like growth factor (IGF) axis and no other endocrine, genetic or organ system disorder. This heterogeneous group of short children without GH deficiency (GHD) includes children with constitutional delay of growth and puberty, familial short stature, or both, as well as those with subtle cartilage and bone dysplasias. In rare cases, ISS is due to IGF molecular abnormalities. In this review we tackle the major challenges in the definition and treatment of ISS.

Loss of ephrinB1 in osteogenic progenitor cells impedes endochondral ossification and compromises bone strength integrity during skeletal development.

PubMed

Nguyen, Thao M; Arthur, Agnieszka; Paton, Sharon; Hemming, Sarah; Panagopoulos, Romana; Codrington, John; Walkley, Carl R; Zannettino, Andrew C W; Gronthos, Stan

2016-12-01

The EphB receptor tyrosine kinase family and their ephrinB ligands have been implicated as mediators of skeletal development and bone homeostasis in humans, where mutations in ephrinB1 contribute to frontonasal dysplasia and coronal craniosynostosis. In mouse models, ephrinB1 has been shown to be a critical factor mediating osteoblast function. The present study examined the functional importance of ephrinB1 during endochondral ossification using the Cre recombination system with targeted deletion of ephrinB1 (EfnB1 fl/fl ) in osteogenic progenitor cells, under the control of the osterix (Osx:Cre) promoter. The Osx:EfnB1 -/- mice displayed aberrant bone growth during embryonic and postnatal skeletal development up to 4weeks of age, when compared to the Osx:Cre controls. Furthermore, compared to the Osx:Cre control mice, the Osx:EfnB1 -/- mice exhibited significantly weaker and less rigid bones, with a reduction in trabecular/ cortical bone formation, reduced trabecular architecture and a reduction in the size of the growth plates at the distal end of the femora from newborn through to 4weeks of age. The aberrant bone formation correlated with increased numbers of tartrate resistant acid phosphatase positive osteoclasts and decreased numbers of bone lining osteoblasts in 4week old Osx:EfnB1 -/- mice, compared to Osx:Cre control mice. Taken together, these observations demonstrate the importance of ephrinB1 signalling between cells of the skeleton required for endochondral ossification. Copyright © 2016 Elsevier Inc. All rights reserved.

Inner ear anomalies and conductive hearing loss in children with Apert syndrome: an overlooked otologic aspect.

PubMed

Zhou, Guangwei; Schwartz, Lynn Thomas; Gopen, Quinton

2009-02-01

To identify the occurrence of inner ear structural anomalies and conductive hearing loss (CHL) in children with Apert syndrome. Retrospective review. Pediatric tertiary referral center. Twenty pediatric patients with Apert syndrome were found; all patients (38/40 ears) had inner ear anomalies. Computerized tomography of the head/temporal bone, pure-tone (including air and bone conduction) audiometry, and tympanometry. Imaging demonstrating inner ear anomalies, including malformations of the cochlea, dilated vestibule, and/or semicircular canal; audiologic findings of air-bone gap(s). Hearing loss was found in 90% of the patients with Apert syndrome, and 80% of them had CHL. Air-bone gaps were found at all frequencies, with larger gaps at low frequencies. Fifty percent (20/40) of the ears had better than 0 dB hearing level bone conduction thresholds at 250 and/or 500 Hz. Normal middle ear pressure and mobility were found in all ears with intact eardrum. Inner ear anomalies were found in all patients, and 90% of them had bilateral involvement. Most frequently observed inner ear anomalies were dilated vestibule, malformed lateral semicircular canal, and cochlear dysplasia. Children with Apert syndrome may present with significant CHL that cannot be explained by minor middle ear pathologies alone. This conductive loss may be, at least partially, attributed to the inner ear anomalies; however, these structural anomalies are usually not recognized in these patients. Failure to close air-bone gap after surgical intervention may raise the suspicion of inner ear anomalies, and computed tomographic scan of the temporal bone can provide definitive proof.

Short stature/short limb skeletal dysplasia with severe combined immunodeficiency and bowing of the femora: report of two patients and review.

PubMed Central

MacDermot, K D; Winter, R M; Wigglesworth, J S; Strobel, S

1991-01-01

We report two patients with severe combined immunodeficiency and short stature/short limb skeletal dysplasia. Case 1 presented at birth with rhizomelic shortening of the extremities and bowing of the femora. She developed clinical signs of severe combined immunodeficiency at 13 months and died at 21 months. Case 2 had severe prenatal shortening and bowing of the extremities and a small, malformed chest. Symptoms of severe combined immunodeficiency and severe failure to thrive developed soon after birth and she died at 5 months. The diagnosis of severe combined immunodeficiency in our patients was based on their clinical course and necropsy findings, supported in case 1 by the results of immune function tests. The results of investigation of immune function (immunoglobulins, lymphocyte subpopulations, lymphocyte function) are very variable in this syndrome as in other variants of severe combined immunodeficiency. Bone histopathology in both patients showed grossly irregular costochondral junctions, but normal transition of proliferating to hypertrophic chondrocytes. These cases belong to early lethal type 1 short limb skeletal dysplasia with severe combined immunodeficiency. Review of previously published cases with severe combined immunodeficiency and well documented skeletal findings show eight patients with prenatal onset of bowing and shortening of the extremities and metaphyseal abnormalities. These include two sib pairs concordant for the skeletal changes. In these cases, adenosine deaminase levels were not reported. An additional four published cases with associated adenosine deaminase deficiency had only mild metaphyseal abnormalities, but subsequently showed no linear growth.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:1999827

Florid cemento-osseous dysplasia: review of an uncommon fibro-osseous lesion of the jaw with important clinical implications.

PubMed

Fenerty, Sarah; Shaw, Wei; Verma, Rahul; Syed, Ali B; Kuklani, Riya; Yang, Jie; Ali, Sayed

2017-05-01

Florid cemento-osseous dysplasia (FCOD) is a rare, benign, multifocal fibro-osseous dysplastic process affecting tooth-bearing areas of the jaw, characterized by replacement of normal trabecular bone with osseous tissue and dense acellular cementum in a fibrous stroma. It is one clinicopathologic variant in a spectrum of related non-neoplastic fibro-osseous lesions known as cemento-osseous dysplasias (CODs), thought to arise from elements of the periodontal ligament. Diagnosis primarily relies upon radiographic and clinical findings; unnecessary biopsy should be avoided, as inoculation with oral pathogens may precipitate chronic infection in these hypovascular lesions. Appropriate management of uncomplicated FCOD consists of periodic radiographic follow-up. Accordingly, it is important that both radiologists and clinicians performing endodontic interventions possess familiarity with this entity in order to prevent misdiagnosis and inappropriate intervention, which may result in a protracted clinical course. Lesions are usually asymptomatic in the absence of infection, typically discovered on routine dental radiographs or imaging performed for unrelated indications. Radiographically, the condition typically manifests as widespread non-expansile intraosseous masses of varying internal lucency and sclerosis that surround the root apices of vital teeth or edentulous areas in the posterior jaw. While all CODs share similar microscopic features, FCOD is distinguished by its multifocal distribution, involving two or more quadrants of the maxilla and mandible, often in a bilateral symmetric fashion. The vast majority of cases are sporadic, though few exhibit an autosomal dominant familial inheritance pattern. In this pictorial review, we discuss the radiologic characteristics of this entity, pertinent clinical and histologic features, differential diagnoses, and management options.

Posterosuperior Placement of a Standard-Sized Cup at the True Acetabulum in Acetabular Reconstruction of Developmental Dysplasia of the Hip With High Dislocation.

PubMed

Xu, Jiawei; Xu, Chen; Mao, Yuanqing; Zhang, Jincheng; Li, Huiwu; Zhu, Zhenan

2016-06-01

We sought to evaluate posterosuperior placement of the acetabular component at the true acetabulum during acetabular reconstruction in patients with Crowe type-IV developmental dysplasia of the hip. Using pelvic computed tomography and image processing, we developed a two-dimensional mapping technique to demonstrate the distribution of preoperative three-dimensional cup coverage at the true acetabulum, determined the postoperative location of the acetabular cup, and calculated postoperative three-dimensional coverage for 16 Crowe type-IV dysplastic hips in 14 patients with a mean age of 52 years (33-78 years) who underwent total hip arthroplasty. Mean follow-up was 6.3 years (5.5-7.3 years). On preoperative mapping, the maximum three-dimensional coverage using a 44-mm cup was 87.31% (77.36%-98.14%). Mapping enabled the successful replacement of 16 hips using a mean cup size of 44.13 mm (42-46 mm) with posterosuperior placement of the cup. Early weight-bearing and no prosthesis revision or loosening during follow-up were achieved in all patients. The postoperative two-dimensional coverage on anteroposterior radiographs and three-dimensional coverage were 96.15% (89.49%-100%) and 83.42% (71.81%-98.50%), respectively. This technique may improve long-term implant survival in patients with Crowe-IV developmental dysplasia of the hip undergoing total hip arthroplasty by allowing the use of durable bearings, increasing host bone coverage, ensuring initial stability, and restoring the normal hip center. Copyright © 2015 Elsevier Inc. All rights reserved.

Ectrodactyly-ectodermal dysplasia clefting syndrome (EEC syndrome).

PubMed

Koul, Monika; Dwivedi, Rahul; Upadhyay, Vinod

2014-01-01

Ectrodactyly-ectodermal dysplasia- clefting syndrome (also k/a. split hand- split foot malformation /split hand-split foot ectodermal dysplasia- cleft syndrome/ectodermal dysplasia cleft lip/cleft palate syndrome) a rare form of ectodermal dysplasia, is an autosomal dominant disorder inherited as a genetic trait and characterized by a triad of (i) ectrodactyly, (ii) ectodermal dysplasia and, (iii) & facial clefts.

Constitutive stimulatory G protein activity in limb mesenchyme impairs bone growth.

PubMed

Karaca, Anara; Malladi, Vijayram Reddy; Zhu, Yan; Tafaj, Olta; Paltrinieri, Elena; Wu, Joy Y; He, Qing; Bastepe, Murat

2018-05-01

GNAS mutations leading to constitutively active stimulatory G protein alpha-subunit (Gsα) cause different tumors, fibrous dysplasia of bone, and McCune-Albright syndrome, which are typically not associated with short stature. Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide receptor, which couples to multiple G proteins including Gsα, leads to short bones with delayed endochondral ossification. It has remained unknown whether constitutive Gsα activity also impairs bone growth. Here we generated mice expressing a constitutively active Gsα mutant (Gsα-R201H) conditionally upon Cre recombinase (cGsα R201H mice). Gsα-R201H was expressed in cultured bone marrow stromal cells from cGsα R201H mice upon adenoviral-Cre transduction. When crossed with mice in which Cre is expressed in a tamoxifen-regulatable fashion (CAGGCre-ER™), tamoxifen injection resulted in mosaic expression of the transgene in double mutant offspring. We then crossed the cGsα R201H mice with Prx1-Cre mice, in which Cre is expressed in early limb-bud mesenchyme. The double mutant offspring displayed short limbs at birth, with narrow hypertrophic chondrocyte zones in growth plates and delayed formation of secondary ossification center. Consistent with enhanced Gsα signaling, bone marrow stromal cells from these mice demonstrated increased levels of c-fos mRNA. Our findings indicate that constitutive Gsα activity during limb development disrupts endochondral ossification and bone growth. Given that Gsα haploinsufficiency also leads to short bones, as in patients with Albright's hereditary osteodystrophy, these results suggest that a tight control of Gsα activity is essential for normal growth plate physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

Immune Thrombocytopenia in Two Unrelated Fanconi Anemia Patients – A Mere Coincidence?

PubMed Central

Karastaneva, Anna; Lanz, Sofia; Wawer, Angela; Behrends, Uta; Schindler, Detlev; Dietrich, Ralf; Burdach, Stefan; Urban, Christian; Benesch, Martin; Seidel, Markus G.

2015-01-01

Thrombocytopenia and pancytopenia, occurring in patients with Fanconi anemia (FA), are interpreted either as progression to bone marrow failure or as developing myelodysplasia. On the other hand, immune thrombocytopenia (ITP) represents an acquired and often self-limiting benign hematologic disorder, associated with peripheral, immune-mediated, platelet destruction requiring different management modalities than those used in congenital bone marrow failure syndromes, including FA. Here, we describe the clinical course of two independent FA patients with atypical – namely immune – thrombocytopenia. While in one patient belonging to complementation group FA-A, the ITP started at 17 months of age and showed a chronically persisting course with severe purpura, responding well to intravenous immunoglobulins (IVIG) and later also danazol, a synthetic androgen, the other patient (of complementation group FA-D2) had a self-limiting course that resolved after one administration of IVIG. No cytogenetic aberrations or bone marrow abnormalities other than FA-typical mild dysplasia were detected. Our data show that acute and chronic ITP may occur in FA patients and impose individual diagnostic and therapeutic challenges in this rare congenital bone marrow failure/tumor predisposition syndrome. The management and a potential context of immune pathogenesis with the underlying marrow disorder are discussed. PMID:26106590

Soluble VEGF isoforms are essential for establishingepiphyseal vascularization and regulating chondrocyte development and survival

PubMed Central

Maes, Christa; Stockmans, Ingrid; Moermans, Karen; Van Looveren, Riet; Smets, Nico; Carmeliet, Peter; Bouillon, Roger; Carmeliet, Geert

2004-01-01

VEGF is crucial for metaphyseal bone vascularization. In contrast, the angiogenic factors required for vascularization of epiphyseal cartilage are unknown, although this represents a developmentally and clinically important aspect of bone growth. The VEGF gene is alternatively transcribed into VEGF120, VEGF164, and VEGF188 isoforms that differ in matrix association and receptor binding. Their role in bone development was studied in mice expressing single isoforms. Here we report that expression of only VEGF164 or only VEGF188 (in VEGF188/188 mice) was sufficient for metaphyseal development. VEGF188/188 mice, however, showed dwarfism, disrupted development of growth plates and secondary ossification centers, and knee joint dysplasia. This phenotype was at least partly due to impaired vascularization surrounding the epiphysis, resulting in ectopically increased hypoxia and massive chondrocyte apoptosis in the interior of the epiphyseal cartilage. In addition to the vascular defect, we provide in vitro evidence that the VEGF188 isoform alone is also insufficient to regulate chondrocyte proliferation and survival responses to hypoxia. Consistent herewith, chondrocytes in or close to the hypoxic zone in VEGF188/188 mice showed increased proliferation and decreased differentiation. These findings indicate that the insoluble VEGF188 isoform is insufficient for establishing epiphyseal vascularization and regulating cartilage development during endochondral bone formation. PMID:14722611

Soluble VEGF isoforms are essential for establishing epiphyseal vascularization and regulating chondrocyte development and survival.

PubMed

Maes, Christa; Stockmans, Ingrid; Moermans, Karen; Van Looveren, Riet; Smets, Nico; Carmeliet, Peter; Bouillon, Roger; Carmeliet, Geert

2004-01-01

VEGF is crucial for metaphyseal bone vascularization. In contrast, the angiogenic factors required for vascularization of epiphyseal cartilage are unknown, although this represents a developmentally and clinically important aspect of bone growth. The VEGF gene is alternatively transcribed into VEGF(120), VEGF(164), and VEGF(188) isoforms that differ in matrix association and receptor binding. Their role in bone development was studied in mice expressing single isoforms. Here we report that expression of only VEGF(164) or only VEGF(188) (in VEGF(188/188) mice) was sufficient for metaphyseal development. VEGF(188/188) mice, however, showed dwarfism, disrupted development of growth plates and secondary ossification centers, and knee joint dysplasia. This phenotype was at least partly due to impaired vascularization surrounding the epiphysis, resulting in ectopically increased hypoxia and massive chondrocyte apoptosis in the interior of the epiphyseal cartilage. In addition to the vascular defect, we provide in vitro evidence that the VEGF(188) isoform alone is also insufficient to regulate chondrocyte proliferation and survival responses to hypoxia. Consistent herewith, chondrocytes in or close to the hypoxic zone in VEGF(188/188) mice showed increased proliferation and decreased differentiation. These findings indicate that the insoluble VEGF(188) isoform is insufficient for establishing epiphyseal vascularization and regulating cartilage development during endochondral bone formation.

A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers.

PubMed

Patel, R M; Nagamani, S C S; Cuthbertson, D; Campeau, P M; Krischer, J P; Shapiro, J R; Steiner, R D; Smith, P A; Bober, M B; Byers, P H; Pepin, M; Durigova, M; Glorieux, F H; Rauch, F; Lee, B H; Hart, T; Sutton, V R

2015-02-01

Osteogenesis imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n = 544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean lumbar spine area bone mineral density (LS aBMD) was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answering questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of 'phenotypic expansion' driven by next-generation sequencing. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Osteogenesis imperfecta.

PubMed

Marini, Joan C; Forlino, Antonella; Bächinger, Hans Peter; Bishop, Nick J; Byers, Peter H; Paepe, Anne De; Fassier, Francois; Fratzl-Zelman, Nadja; Kozloff, Kenneth M; Krakow, Deborah; Montpetit, Kathleen; Semler, Oliver

2017-08-18

Skeletal deformity and bone fragility are the hallmarks of the brittle bone dysplasia osteogenesis imperfecta. The diagnosis of osteogenesis imperfecta usually depends on family history and clinical presentation characterized by a fracture (or fractures) during the prenatal period, at birth or in early childhood; genetic tests can confirm diagnosis. Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure. In the past decade, (mostly) recessive, dominant and X-linked defects in a wide variety of genes encoding proteins involved in type I collagen synthesis, processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells have been shown to cause osteogenesis imperfecta. The large number of causative genes has complicated the classic classification of the disease, and although a new genetic classification system is widely used, it is still debated. Phenotypic manifestations in many organs, in addition to bone, are reported, such as abnormalities in the cardiovascular and pulmonary systems, skin fragility, muscle weakness, hearing loss and dentinogenesis imperfecta. Management involves surgical and medical treatment of skeletal abnormalities, and treatment of other complications. More innovative approaches based on gene and cell therapy, and signalling pathway alterations, are under investigation.

[Experimental surgical model of hydrocele for the use of sclerotherapy].

PubMed

Castillo Jimeno, J M; Santiago, A M; Sebastián, J L; Ruiz, J L; Pérez Unzu, A; Puras, A; Marcotegui, F

1990-10-01

Sclerosant therapy for different pathological conditions (testicular hydrocele, pneumothorax) is a little known and scantily used procedure in the clinical setting. We have developed a surgical procedure in the dog that permits reproducing adult hydrocele. This experimental model is useful for morphometric assessment of the sclerosant effects of the commonly used agents (magnesium silicate hydrate, carbolic acid, ethanolamine oleate, hydroxytetracycline chlorhydrate and quinacrine chlorhydrate). Our results show that the degree of sclerosis achieved with quinacrine and hydrotetracycline is significantly superior to that obtained with other agents.

18F-FDG avid Sclerosing Angiomatoid Nodular Transformation (SANT) of spleen on PET-CT - a rare mimicker of metastasis.

PubMed

Sharma, Punit

2018-01-01

Sclerosing Angiomatoid Nodular Transformation (SANT) is a rare benign vascular tumor of spleen. It consists of multiple angiomatoid nodules surrounded by dense fibrous tissue that often coalesces centrally to form a scar, which is considered to be a characteristic feature. These are usually asymptomatic and incidentally detected on imaging for other underlying pathology. SANTs can be 18F-Fluorodeoxyglucose (18F-FDG) avid on positron emission tomography-computed tomography (PET-CT) and thus can lead to false positive finding in oncological patients.

MRI and MR spectroscopy findings of a case of subacute sclerosing panencephalitis affecting the corpus callosum.

PubMed

Öztürk, Mehmet; Sığırcı, Ahmet; Yakıncı, Cengiz

2015-07-10

Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressive, fatal, inflammatory and neurodegenerative disease that is seen mostly in children and young adolescents, and primarily affects the parieto-occipital lobes. The corpus callosum, cerebellum and basal ganglia are less frequently involved. MR spectroscopy (MRS) may illustrate the pathophysiological features of SSPE. To the best of our knowledge, this is the second report of MRS findings of corpus callosum involvement in a stage 3 SSPE case. 2015 BMJ Publishing Group Ltd.

Subacute Sclerosing Panencephalitis Presenting with Isolated Positive Psychotic and Catatonic Symptoms

PubMed Central

Parmar, Arpit; Ranjan, Rajeev; Sagar, Rajesh

2017-01-01

Subacute sclerosing panencephalitis (SSPE) is a rare slowly progressing neurological illness. Although patients with SSPE initially present with symptoms such as myoclonic jerks, cognitive decline, and personality/behavioral changes usually, rarely pure psychiatric symptoms (e.g., mania, psychosis, and catatonia) have also been reported during the initial course of the illness. We report an unusual case of an adolescent with SSPE presenting with prominent positive psychotic and catatonic symptoms with the absence of classical symptoms of SSPE in initial course of illness and further discussed the relevant literature. PMID:28852257

Subacute sclerosing panencephalitis: a case report.

PubMed

Praticò, A D; Saporito, M; Iacono, O; Castellano-Chiodo, D; Pavone, P

2011-02-01

Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder of childhood and early adolescence caused by persistent defective measles virus. Clinical manifestations appear many years after the acute measles infection. The incidence of SSPE has substantially declined after the introduction of an effective vaccine. We report a case of a child with SSPE that began with atonia, dysarthria, and intellectual deterioration without the presence of any particular EEG anomalies. We have reported this girl who was affected by this severe affliction in the hope that, because of the rarity of SSPE, it would not go undiagnosed.

Subacute Sclerosing Panencephalitis Presenting with Isolated Positive Psychotic and Catatonic Symptoms.

PubMed

Parmar, Arpit; Ranjan, Rajeev; Sagar, Rajesh

2017-01-01

Subacute sclerosing panencephalitis (SSPE) is a rare slowly progressing neurological illness. Although patients with SSPE initially present with symptoms such as myoclonic jerks, cognitive decline, and personality/behavioral changes usually, rarely pure psychiatric symptoms (e.g., mania, psychosis, and catatonia) have also been reported during the initial course of the illness. We report an unusual case of an adolescent with SSPE presenting with prominent positive psychotic and catatonic symptoms with the absence of classical symptoms of SSPE in initial course of illness and further discussed the relevant literature.

Use of a sclerosing agent (1% polidocanol) to treat an orbital mucocele in a dog.

PubMed

Stuckey, Jane Ashley; Miller, William W; Almond, Gregory T

2012-05-01

A case of a salivary gland mucocele in a dog causing nonpainful exopthalmos with dorsolateral deviation of the globe and protrusion of the third eyelid. Diagnosis was made via ultrasound and confirmed with computed tomography. Aspiration of the cystic material along with injection of a sclerosing agent, 1% polidocanol (Aethoxysklerol), was used to destroy the mucocele. Follow-up monthly examination post injection confirmed resolution of clinical signs to date, namely abnormal globe position, with no complications observed. © 2011 American College of Veterinary Ophthalmologists.

Chondrocyte-Specific Inhibition of β-Catenin Signaling Leads to Dysplasia of the Caudal Vertebrae in Mice

PubMed Central

Shu, Bing; Li, Tian-Fang; Li, Xiao-Feng; Tang, De-Zhi; Zhang, Yejia; Shi, Qi

2013-01-01

Study Design. To inhibit β-catenin specifically signaling in chondrocytes Col2-ICAT transgenic mice were generated. Anomalies in caudal vertebrae were detected during embryonic and postnatal stages of Col2-ICAT transgenic mice. Objective. To determine the role of canonical β-catenin signaling in caudal vertebral development. Summary of Background Data. β-catenin signaling plays a critical role in skeletal development. Col2-ICAT transgenic mice were generated to selectively block β-catenin signaling by overexpression of the ICAT gene in chondrocytes. Methods. Tails of E16.5 transgenic embryos and adult Col2-ICAT transgenic mice and their wild-type littermates were collected and analyzed. Skeletal preparation, 3-dimensional micro-computed tomographic and histological analyses were performed to evaluate changes in the structure of caudal vertebrae. Bromodeoxyuridine labeling was performed to evaluate changes in chondrocyte proliferation in caudal vertebrae. Results. Skeletal preparation and 3-dimensional micro-computed tomographic analyses revealed bone deformation and angulated deformities in tail tissue in Col2-ICAT transgenic mice. Histological studies revealed abnormal bone development and dysplastic caudal vertebrae in Col2-ICAT transgenic mice. Inhibition of β-catenin signaling in cartilage resulted in vertebral dysplasia leading to aberrant resegmenting process. Thus, 2 poorly developed sclerotomes failed to fuse to form a complete vertebrae. BrdU labeling revealed a decreased chondrocyte proliferation in both cartilageous templates of transgenic embryos and the growth plate of adult Col2-ICAT transgenic mice. Conclusion. Wnt/β-catenin signaling plays an important role in vertebral development. Inhibition of β-catenin signaling in chondrocytes results in caudal vertebra deformity in mice, which may occur as early as in the stage of sclerotome formation. Level of Evidence: N/A PMID:24026150

De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise.

PubMed

Writzl, Karin; Maver, Ales; Kovačič, Lidija; Martinez-Valero, Paula; Contreras, Laura; Satrustegui, Jorgina; Castori, Marco; Faivre, Laurence; Lapunzina, Pablo; van Kuilenburg, André B P; Radović, Slobodanka; Thauvin-Robinet, Christel; Peterlin, Borut; Del Arco, Araceli; Hennekam, Raoul C

2017-11-02

A series of simplex cases have been reported under various diagnoses sharing early aging, especially evident in congenitally decreased subcutaneous fat tissue and sparse hair, bone dysplasia of the skull and fingers, a distinctive facial gestalt, and prenatal and postnatal growth retardation. For historical reasons, we suggest naming the entity Fontaine syndrome. Exome sequencing of four unrelated affected individuals showed that all carried the de novo missense variant c.649C>T (p.Arg217Cys) or c.650G>A (p.Arg217His) in SLC25A24, a solute carrier 25 family member coding for calcium-binding mitochondrial carrier protein (SCaMC-1, also known as SLC25A24). SLC25A24 allows an electro-neutral and reversible exchange of ATP-Mg and phosphate between the cytosol and mitochondria, which is required for maintaining optimal adenine nucleotide levels in the mitochondrial matrix. Molecular dynamic simulation studies predict that p.Arg217Cys and p.Arg217His narrow the substrate cavity of the protein and disrupt transporter dynamics. SLC25A24-mutant fibroblasts and cells expressing p.Arg217Cys or p.Arg217His variants showed altered mitochondrial morphology, a decreased proliferation rate, increased mitochondrial membrane potential, and decreased ATP-linked mitochondrial oxygen consumption. The results suggest that the SLC25A24 mutations lead to impaired mitochondrial ATP synthesis and cause hyperpolarization and increased proton leak in association with an impaired energy metabolism. Our findings identify SLC25A24 mutations affecting codon 217 as the underlying genetic cause of human progeroid Fontaine syndrome. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Illness Perceptions are Associated with Quality of Life in Patients with Fibrous Dysplasia.

PubMed

Majoor, B C J; Andela, C D; Quispel, C R; Rotman, M; Dijkstra, P D S; Hamdy, N A T; Kaptein, A A; Appelman-Dijkstra, N M

2018-01-01

Fibrous dysplasia (FD) is a rare bone disorder in which normal bone is replaced by fibrous tissue resulting in pain, deformities, pathological fractures or asymptomatic disease. Illness perceptions are patients' cognitions and emotions about their illness and its treatment, which may impact on Quality of Life (QoL). Here, we explore illness perceptions in patients with FD compared to other disorders, identify factors associated with illness perceptions and evaluate their relationship with QoL. Ninety-seven out of 138 eligible patients from the LUMC FD cohort completed the Illness Perception Questionnaire-Revised (IPQ-R) and the Short Form-36 (SF-36). Age, Gender, Skeletal Burden Score (SBS), FGF-23 levels, type of FD and SF-36 scores were analysed for an association with illness perceptions. We observed significant (p < 0.01) differences in patients' illness perceptions between FD subtypes in the domains: identity, timeline acute/chronic and consequences. Patients with craniofacial FD reported to perceive more consequences (p = 0.022). High SBS was associated with perceiving more negative consequences and attributing the cause of FD to psychological factors (p < 0.01), and high FGF-23 levels with attributing more symptoms to the disease and perceiving more consequences (p < 0.01). The IPQ-R domain identity, timeline acute/chronic, timeline cyclical, consequences, emotional representations and treatment control were significantly associated with impairments in QoL. Illness perceptions in patients with FD relate to QoL, differ from those in patients with other disorders, and are associated with disease severity. Identifying and addressing maladaptive illness perceptions may improve quality of life in patients with FD.

Florid Cemento-osseous Dysplasia: A Case of Misdiagnosis.

PubMed

Delai, Débora; Bernardi, Anarela; Felippe, Gabriela Santos; da Silveira Teixeira, Cleonice; Felippe, Wilson Tadeu; Santos Felippe, Mara Cristina

2015-11-01

Florid cemento-osseous dysplasia (FCOD) belongs to the group of fibro-osseous lesions in which normal bone is replaced by fibrous connective tissue and calcified cementum tissue of the avascular type. Among the various types of fibro-osseous lesions, FCOD is one of the most commonly encountered diseases in clinical practice and may involve 3 or 4 of the quadrants. FCOD is located in the periapical regions of teeth, and the lesions are predominantly radiolucent (osteolytic phase), become mixed over time (cementoblast phase), and ultimately become radiopaque (osteogenic phase) with a thin radiolucent peripheral halo. The characteristics of FCOD in the initial stages are similar to those of periapical lesions of inflammatory origin, which may lead to misdiagnosis. A 38-year-old woman sought dental care because of complaints of pain on the right side of her face. A clinical examination revealed no marked alterations; a panoramic radiograph was therefore requested and revealed the presence of radiolucent lesions associated with the periapical regions of some of the lower teeth. Thus, the professional referred the patient for endodontic treatment of the associated teeth with the justification that the lesions were of endodontic origin. However, the endodontist found that the teeth responded positively to a sensitivity test. The initial diagnosis could have resulted in unnecessary root canal treatment, but after careful clinical, radiographic, and tomographic assessments by different professionals, FCOD was diagnosed, conservatively treated, and regularly monitored. It is important that dentists have a basic knowledge of the various injuries that affect the jaw bones to prevent errors in diagnosis and treatment and to promote oral health. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Treatment of shepherd’s crook deformity in patients with polyostotic fibrous dysplasia using a new type of custom made retrograde intramedullary nail: a technical note

PubMed Central

Hefti, F.; Donnan, L.; Krieg, A. H.

2017-01-01

Aims The severe form of coxa vara, the ‘shepherd’s crook deformity’, is always a consequence of a locally extensive form of polyostotic fibrous dysplasia (or McCune-Albright syndrome). Treatment of this deformity is a challenge. The soft bone does not tolerate any implant that depends on the stability of the cortical bone (like plates or external fixators). Intramedullary nails are the most appropriate implants for stabilisation, but if they are inserted from the greater trochanter, they cannot correct the varus deformity enough. Patients and Methods We have developed a special intramedullary nail that can be inserted from the osteotomy site and can be driven retrograde into the femoral neck in an appropriate valgus position. We have operated 15 legs in 13 patients. The average age at surgery was 14 years and 5 months (6 to 28.9). In all, 11 femora had been operated before (unsuccessfully) with various implants. Results The average follow-up was 54.2 months (7 to 132). The average correction of the neck/(distal) shaft angle was 57.5° (10° to 80°) ( = 72.8%). While pre-operatively none of the patients was able to walk without aid, at follow-up only one patient was unable to walk, three used the aid of crutches because of tibial lesions and one patient had an increased external rotation of the leg. At follow-up, most patients were free of pain. One implant broke and had to be replaced. Conclusion This new operative method offers the possibility of efficient correction and stabilisation of this severe and difficult deformation. PMID:28439311

Three-Dimensional Host Bone Coverage in Total Hip Arthroplasty for Crowe Types II and III Developmental Dysplasia of the Hip.

PubMed

Xu, Jiawei; Qu, Xinhua; Li, Huiwu; Mao, Yuanqing; Yu, Degang; Zhu, Zhenan

2017-04-01

Recommendations for minimum cup coverage based on anteroposterior radiographs are widely used as an intraoperative guide in total hip arthroplasty for patients with developmental dysplasia of the hip. The purpose of this study was to examine the validity of two-dimensional (2D) measurement of coverage with three-dimensional (3D) coverage and to identify parameters for determining the 3D coverage during surgery. We developed a technique to accurately reproduce the intraoperative anatomic geometry of the dysplastic acetabulum and measure the 3D cup coverage postoperatively. With this technique, we retrospectively analyzed the difference and correlation between 2D and 3D measurements of native bone coverage in 35 patients (45 hips) with Crowe II or III DDH. Linear regression analysis was performed to examine the intraoperative parameters related to coverage. The mean follow-up period was 7.64 years (range, 6.1-9.5 years). There was a significant difference and a fair correlation between 2D and 3D measurements. The 2D measurement underestimated the 3D cup coverage by approximately 13%. An excellent linear relationship was noted between the 3D coverage/uncoverage and the height of the uncovered portion (R 2  = 0.8440, P < .0001). There was no case of loosening or revision during the follow-up. Current minimum cup coverage recommendations based on 2D radiograph measurements should not be used as a direct intraoperative guide. The height of the uncovered portion is a useful parameter to determine the 3D coverage during surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Penile sclerosing lipogranulomas and disfigurement from use of "1Super Extenze" among Laotian immigrants.

PubMed

Manny, Ted; Pettus, Joseph; Hemal, Ashok; Marks, Malcolm; Mirzazadeh, Majid

2011-12-01

Subcutaneous penile injection of various oils for penile augmentation has been described among men in Laos. We have now treated three Laotian immigrants with penile disfigurement secondary to sclerosing lipogranulomas, also known as paraffinoma, induced by injection of a mineral oil compound marketed as "1Super Extenze," which they purchased in the United States. This series describes the clinical course and management of complications associated with the use of "1Super Extenze" in three Laotian men. Surgeons excised all grossly affected tissue and performed reconstruction using skin grafting, Z-plasty, and tissue advancement, respectively. Tissue from the penile shaft of each patient and a local lymph node in one patient was examined microscopically. Mass spectroscopy was performed on an aliquot of "1Super Extenze." Urinary function, sexual function, and cosmesis of the three reported cases, chemical composition of "1Super Extenze," and microscopic analysis of penile and regional lymphatic tissue. Short-term cosmetic and functional outcomes were acceptable after surgical intervention. Histologic findings consistent with sclerosing lipogranulomas were seen in specimens from affected subcutaneous and lymphatic tissue. "1Super Extenze" proved to be composed of mineral oil with tocopherol acetate (vitamin E). Injection of "1Super Extenze" into the penile shaft results in sclerosing lipogranulomas, which can cause severe sexual and urinary complications. Surgical resection of all grossly involved tissue with appropriate reconstruction can mitigate these problems. This series supports previous recommendations in the literature that men should avoid the use of non-medical foreign bodies and fillers as means of penile augmentation. © 2010 International Society for Sexual Medicine.

Computer aided diagnosis and treatment planning for developmental dysplasia of the hip

NASA Astrophysics Data System (ADS)

Li, Bin; Lu, Hongbing; Cai, Wenli; Li, Xiang; Meng, Jie; Liang, Zhengrong

2005-04-01

The developmental dysplasia of the hip (DDH) is a congenital malformation affecting the proximal femurs and acetabulum that are subluxatable, dislocatable, and dislocated. Early diagnosis and treatment is important because failure to diagnose and improper treatment can result in significant morbidity. In this paper, we designed and implemented a computer aided system for the diagnosis and treatment planning of this disease. With the design, the patient received CT (computed tomography) or MRI (magnetic resonance imaging) scan first. A mixture-based PV partial-volume algorithm was applied to perform bone segmentation on CT image, followed by three-dimensional (3D) reconstruction and display of the segmented image, demonstrating the special relationship between the acetabulum and femurs for visual judgment. Several standard procedures, such as Salter procedure, Pemberton procedure and Femoral Shortening osteotomy, were simulated on the screen to rehearse a virtual treatment plan. Quantitative measurement of Acetabular Index (AI) and Femoral Neck Anteversion (FNA) were performed on the 3D image for evaluation of DDH and treatment plans. PC graphics-card GPU architecture was exploited to accelerate the 3D rendering and geometric manipulation. The prototype system was implemented on PC/Windows environment and is currently under clinical trial on patient datasets.

Cutis laxa and excessive bone growth due to de novo mutations in PTDSS1.

PubMed

Piard, Juliette; Lespinasse, James; Vlckova, Marketa; Mensah, Martin A; Iurian, Sorin; Simandlova, Martina; Malikova, Marcela; Bartsch, Oliver; Rossi, Massimiliano; Lenoir, Marion; Nugues, Frédérique; Mundlos, Stefan; Kornak, Uwe; Stanier, Philip; Sousa, Sérgio B; Van Maldergem, Lionel

2018-03-01

The cutis laxa syndromes are multisystem disorders that share loose redundant inelastic and wrinkled skin as a common hallmark clinical feature. The underlying molecular defects are heterogeneous and 13 different genes have been involved until now, all of them being implicated in elastic fiber assembly. We provide here molecular and clinical characterization of three unrelated patients with a very rare phenotype associating cutis laxa, facial dysmorphism, severe growth retardation, hyperostotic skeletal dysplasia, and intellectual disability. This disorder called Lenz-Majewski syndrome (LMS) is associated with gain of function mutations in PTDSS1, encoding an enzyme involved in phospholipid biosynthesis. This report illustrates that LMS is an unequivocal cutis laxa syndrome and expands the clinical and molecular spectrum of this group of disorders. In the neonatal period, brachydactyly and facial dysmorphism are two early distinctive signs, later followed by intellectual disability and hyperostotic skeletal dysplasia with severe dwarfism allowing differentiation of this condition from other cutis laxa phenotypes. Further studies are needed to understand the link between PTDSS1 and extra cellular matrix assembly. © 2018 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

A Case of Atypical McCune-Albright Syndrome with Vaginal Bleeding

PubMed Central

Rostampour, Noushin; Hashemipour, Mahin; Kelishadi, Roya; Hovsepian, Silva; Hekmatnia, Ali

2011-01-01

Background McCune-Albright syndrome (MAS) is a rare non-inherited disorder characterized by the clinical triad of precocious puberty, cafe-au-lait skin lesions, and fibrous dysplasia of bone. Case Presentation We report a girl with MAS, presenting initially with vaginal bleeding at the age of 17 months. Ultrasonography revealed unilateral ovarian cysts and ureteral and ovarian enlargement. Considering the clinical and paraclinical findings, the patient diagnosed as a case of gonadotropin-independent precocious puberty was treated with medroxy-progestrone acetate (MPA) for three months. During the follow up, recurrent episodes of bleeding, ovarian activation and cyst formation, as well as breast size development were reported. At the age of 5.5 years, fibrous dysplasia was detected, which in coexistence with precocious puberty confirmed the diagnosis of MAS. The patient had no cafe-au-lait skin macles during follow up. Conclusion Considering that clinical manifestations of MAS appear later in the course of recurrent periods of ovarian activation and cyst formation, a careful clinical observation and follow up of patients is necessary and the diagnosis of MAS must be kept in mind in cases with gonadotropin-independent precocious puberty. PMID:23056821

[Localized scleroderma (morphea) in childhood].

PubMed

Weibel, L

2012-02-01

Localized scleroderma or morphea is a sclerosing connective tissue disease of the skin, which may affect underlying tissues such as subcutis, muscle and bone. Many patients show extracutaneous symptoms and antinuclear antibodies, however, secondary transformation into systemic sclerosis does not occur. Localized scleroderma usually begins in childhood with a wide variation in its clinical spectrum. The linear variant is the most common subtype in children, associated with a progressive course and increased risk of complications. The disease may progress over years and result in severe functional and cosmetic disability. The etiology of localized scleroderma remains unknown. A genetic background is suspected, while triggers such as trauma, vaccinations and infections may lead to secondary immunologic phenomena. Localized scleroderma often remains unrecognized for a long time, resulting in substantial delay in treatment. The combination of systemic corticosteroids and methotrexate has been established as first-line therapy for progressive (usually linear) disease, whereas phototherapy (UVA-1 or UVB-narrow band) is suitable for adolescents with superficial circumscribed subtypes.

Microbubbles in macrocysts - Contrast-enhanced ultrasound assisted sclerosant therapy of a congenital macrocystic lymphangioma: a case report.

PubMed

Menendez-Castro, Carlos; Zapke, Maren; Fahlbusch, Fabian; von Goessel, Heiko; Rascher, Wolfgang; Jüngert, Jörg

2017-07-06

Congenital cystic lymphangiomas are benign malformations due to a developmental disorder of lymphatic vessels. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option. For an appropriate application of OK-432, a detailed knowledge about the structure and composition of the congenital cystic lymphangioma is essential. SonoVue® is a commercially available contrast agent commonly used in sonography by intravenous and intracavitary application. Here we report the case of 2 month old male patient with a large thoracic congenital cystic lymphangioma. Preinterventional imaging of the malformation was performed by contrast-enhanced ultrasound after intracavitary application of SonoVue® immediately followed by a successful sclerotherapy with OK-432. Contrast agent-enhanced ultrasound imaging offers a valuable option to preinterventionally clarify the anatomic specifications of a congenital cystic lymphangioma in more detail than by single conventional sonography. By the exact knowledge about the composition and especially about the intercystic communications of the lymphangioma sclerosant therapy becomes safer and more efficient.

[Diagnostic values of bronchoscopy and multi-slice spiral CT for congenital dysplasia of the respiratory system in infants: a comparative study].

PubMed

Wang, Xing-Lu; Huang, Ying; Li, Qu-Bei; Dai, Ji-Hong

2013-09-01

To investigate and compare the diagnostic values of bronchoscopy and multi-slice spiral computed tomography (CT) for congenital dysplasia of the respiratory system in infants. Analysis was performed on the clinical data, bronchoscopic findings and multi-slice spiral CT findings of 319 infants (≤1 years old) who underwent bronchoscopy and/or multi-slice spiral CT and were diagnosed with congenital dysplasia of the respiratory system. A total of 476 cases of congenital dysplasia of the respiratory system were found in the 319 infants, including primary dysplasia of the respiratory system (392 cases) and compressive dysplasia of the respiratory system (84 cases). Of the 392 cases of primary dysplasia of the respiratory system, 225 (57.4%) were diagnosed by bronchoscopy versus 167 (42.6%) by multi-slice spiral CT. There were significant differences in etiological diagnosis between bronchoscopy and multi-slice spiral CT in infants with congenital dysplasia of the respiratory system (P<0.05). All 76 cases of primary dysplasia of the respiratory system caused by tracheobronchomalacia were diagnosed by bronchoscopy and all 17 cases of primary dysplasia of the respiratory system caused by lung tissue dysplasia were diagnosed by multi-slice spiral CT. Of the 84 cases of compressive dysplasia of the respiratory system, 74 cases were diagnosed by multi-slice spiral CT and only 10 cases were diagnosed by bronchoscopy. Compared with multi-slice spiral CT, bronchoscopy can detect primary dysplasia of the respiratory system more directly. Bronchoscopy is valuable in the confirmed diagnosis of tracheobronchomalacia. Multi-slice spiral CT has a higher diagnostic value for lung tissue dysplasia than bronchoscopy.

Impact of enzyme replacement therapy and hematopoietic stem cell transplantation in patients with Morquio A syndrome

PubMed Central

Tomatsu, Shunji; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Shimada, Tsutomu; Bober, Michael B; Chinen, Yasutsugu; Yabe, Hiromasa; Montaño, Adriana M; Giugliani, Roberto; Kubaski, Francyne; Yasuda, Eriko; Rodríguez-López, Alexander; Espejo-Mojica, Angela J; Sánchez, Oscar F; Mason, Robert W; Barrera, Luis A; Mackenzie, William G; Orii, Tadao

2015-01-01

Patients with mucopolysaccharidosis IVA (MPS IVA) can present with systemic skeletal dysplasia, leading to a need for multiple orthopedic surgical procedures, and often become wheelchair bound in their teenage years. Studies on patients with MPS IVA treated by enzyme replacement therapy (ERT) showed a sharp reduction on urinary keratan sulfate, but only modest improvement based on a 6-minute walk test and no significant improvement on a 3-minute climb-up test and lung function test compared with the placebo group, at least in the short-term. Surgical remnants from ERT-treated patients did not show reduction of storage materials in chondrocytes. The impact of ERT on bone lesions in patients with MPS IVA remains limited. ERT seems to be enhanced in a mouse model of MPS IVA by a novel form of the enzyme tagged with a bone-targeting moiety. The tagged enzyme remained in the circulation much longer than untagged native enzyme and was delivered to and retained in bone. Three-month-old MPS IVA mice treated with 23 weekly infusions of tagged enzyme showed marked clearance of the storage materials in bone, bone marrow, and heart valves. When treatment was initiated at birth, reduction of storage materials in tissues was even greater. These findings indicate that specific targeting of the enzyme to bone at an early stage may improve efficacy of ERT for MPS IVA. Recombinant N-acetylgalactosamine-6-sulfate sulfatase (GALNS) in Escherichia coli BL21 (DE3) (erGALNS) and in the methylotrophic yeast Pichia pastoris (prGALNS) has been produced as an alternative to the conventional production in Chinese hamster ovary cells. Recombinant GALNS produced in microorganisms may help to reduce the high cost of ERT and the introduction of modifications to enhance targeting. Although only a limited number of patients with MPS IVA have been treated with hematopoietic stem cell transplantation (HSCT), beneficial effects have been reported. A wheelchair-bound patient with a severe form of MPS IVA was treated with HSCT at 15 years of age and followed up for 10 years. Radiographs showed that the figures of major and minor trochanter appeared. Loud snoring and apnea disappeared. In all, 1 year after bone marrow transplantation, bone mineral density at L2–L4 was increased from 0.372 g/cm2 to 0.548 g/cm2 and was maintained at a level of 0.48±0.054 for the following 9 years. Pulmonary vital capacity increased approximately 20% from a baseline of 1.08 L to around 1.31 L over the first 2 years and was maintained thereafter. Activity of daily living was improved similar to the normal control group. After bilateral osteotomies, a patient can walk over 400 m using hip–knee–ankle–foot orthoses. This long-term observation of a patient shows that this treatment can produce clinical improvements although bone deformity remained unchanged. In conclusion, ERT is a therapeutic option for MPS IVA patients, and there are some indications that HSCT may be an alternative to treat this disease. However, as neither seems to be a curative therapy, at least for the skeletal dysplasia in MPS IVA patients, new approaches are investigated to enhance efficacy and reduce costs to benefit MPS IVA patients. PMID:25897204

FGFR3-related condition: a skeletal dysplasia with similarities to thanatophoric dysplasia and SADDAN due to Lys650Met.

PubMed

Farmakis, Shannon G; Shinawi, Marwan; Miller-Thomas, Michelle; Radmanesh, Alireza; Herman, Thomas E

2015-03-01

Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene account for six related skeletal dysplasia conditions: achondroplasia, hypochondroplasia, thanatophoric dysplasia types 1 and 2, SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans), and platyspondylic lethal skeletal dysplasia, San Diego type. This group of disorders has very characteristic clinical and radiologic features, which distinguish them from other skeletal dysplasias. They display a spectrum of severity in the skeletal findings, ranging from relatively mild hypochondroplasia to lethal thanatophoric dysplasia. We report a patient who has the missense FGFR3 mutation, Lys650Met, previously reported in association only with SADDAN, who exhibits some findings similar to both thanatophoric dysplasia (types 1 and 2) in addition to those findings characteristic of SADDAN.

Long-Term Clinical Outcome and Carrier Phenotype in Autosomal Recessive Hypophosphatemia Caused by a Novel DMP1 Mutation

PubMed Central

Mäkitie, Outi; Pereira, Renata C; Kaitila, Ilkka; Turan, Serap; Bastepe, Murat; Laine, Tero; Kröger, Heikki; Cole, William G; Jüppner, Harald

2010-01-01

Homozygous inactivating mutations in DMP1 (dentin matrix protein 1), the gene encoding a noncollagenous bone matrix protein expressed in osteoblasts and osteocytes, cause autosomal recessive hypophosphatemia (ARHP). Herein we describe a family with ARHP owing to a novel homozygous DMP1 mutation and provide a detailed description of the associated skeletal dysplasia and carrier phenotype. The two adult patients with ARHP, a 78-year-old man and his 66-year-old sister, have suffered from bone pain and lower extremity varus deformities since early childhood. With increasing age, both patients developed severe joint pain, contractures, and complete immobilization of the spine. Radiographs showed short and deformed long bones, significant cranial hyperostosis, enthesopathies, and calcifications of the paraspinal ligaments. Biochemistries were consistent with hypophosphatemia owing to renal phosphate wasting; markers of bone turnover and serum fibroblast growth factor 23 (FGF-23) levels were increased significantly. Nucleotide sequence analysis of DMP1 revealed a novel homozygous mutation at the splice acceptor junction of exon 6 (IVS5-1G > A). Two heterozygous carriers of the mutation also showed mild hypophosphatemia, and bone biopsy in one of these individuals showed focal areas of osteomalacia. In bone, DMP1 expression was absent in the homozygote but normal in the heterozygote, whereas FGF-23 expression was increased in both subjects but higher in the ARHP patient. The clinical and laboratory observations in this family confirm that DMP1 has an important role in normal skeletal development and mineral homeostasis. The skeletal phenotype in ARHP may be significantly more severe than in other forms of hypophosphatemic rickets. © 2010 American Society for Bone and Mineral Research. PMID:20499351

Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength.

PubMed

Sinder, B P; White, L E; Salemi, J D; Ominsky, M S; Caird, M S; Marini, J C; Kozloff, K M

2014-08-01

Treatments to reduce fracture rates in adults with osteogenesis imperfecta are limited. Sclerostin antibody, developed for treating osteoporosis, has not been explored in adults with OI. This study demonstrates that treatment of adult OI mice respond favorably to sclerostin antibody therapy despite retention of the OI-causing defect. Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk. Although OI fracture risk is greatest before puberty, adults with OI remain at risk of fracture. Antiresorptive bisphosphonates are commonly used to treat adult OI, but have shown mixed efficacy. New treatments which consistently improve bone mass throughout the skeleton may improve patient outcomes. Neutralizing antibodies to sclerostin (Scl-Ab) are a novel anabolic therapy that have shown efficacy in preclinical studies by stimulating bone formation via the canonical wnt signaling pathway. The purpose of this study was to evaluate Scl-Ab in an adult 6 month old Brtl/+ model of OI that harbors a typical heterozygous OI-causing Gly > Cys substitution on Col1a1. Six-month-old WT and Brtl/+ mice were treated with Scl-Ab (25 mg/kg, 2×/week) or Veh for 5 weeks. OCN and TRACP5b serum assays, dynamic histomorphometry, microCT and mechanical testing were performed. Adult Brtl/+ mice demonstrated a strong anabolic response to Scl-Ab with increased serum osteocalcin and bone formation rate. This anabolic response led to improved trabecular and cortical bone mass in the femur. Mechanical testing revealed Scl-Ab increased Brtl/+ femoral stiffness and strength. Scl-Ab was successfully anabolic in an adult Brtl/+ model of OI.

Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci

PubMed Central

Melum, Espen; Franke, Andre; Schramm, Christoph; Weismüller, Tobias J; Gotthardt, Daniel Nils; Offner, Felix A; Juran, Brian D; Laerdahl, Jon K; Labi, Verena; Björnsson, Einar; Weersma, Rinse K; Henckaerts, Liesbet; Teufel, Andreas; Rust, Christian; Ellinghaus, Eva; Balschun, Tobias; Boberg, Kirsten Muri; Ellinghaus, David; Bergquist, Annika; Sauer, Peter; Ryu, Euijung; Hov, Johannes Roksund; Wedemeyer, Jochen; Lindkvist, Björn; Wittig, Michael; Porte, Robert J; Holm, Kristian; Gieger, Christian; Wichmann, H-Erich; Stokkers, Pieter; Ponsioen, Cyriel Y; Runz, Heiko; Stiehl, Adolf; Wijmenga, Cisca; Sterneck, Martina; Vermeire, Severine; Beuers, Ulrich; Villunger, Andreas; Schrumpf, Erik; Lazaridis, Konstantinos N; Manns, Michael P; Schreiber, Stefan; Karlsen, Tom H

2015-01-01

Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4–7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 × 10−16 and P = 4.1 × 10−8, respectively). PMID:21151127

A new sclerosant therapy for testicular hydrocele with aspiration and injection of OK-432.

PubMed

Yamamoto, M; Hibi, H; Miyake, K

1994-01-01

Twenty patients with testicular hydrocele were treated with a new sclerosing therapy consisting of intrascrotal injection of OK-432 (group A Streptococcus pyogenes of human origin). The median observation period after treatment was 6 months (range 2-13 months). Eighteen patients required only one treatment. Two patients had recurrences and received repeat injection. There have been no serious side effects except for fever of 2-3 days' duration and local inflammatory reaction. Sclerotherapy with OK-432 is an efficient and easy method which can be recommended as a primary treatment for hydrocele.

[Primary sclerosing cholangitis associated with Sjögren's syndrome, retroperitoneal fibrosis and chronic pancreatitis. Report of a case].

PubMed

Barreda, F; Contardo, C; León, A; Navarrete, J; Figueroa, R; Attanasio, F

1989-01-01

Primary Sclerosing Cholangitis (PSC) is an unusual chronic, cholestatic disease of unknown etiology, more frequently seen in young adults in close relationship with Chronic Ulcerative Colitis. We report the case of a 30 year old woman, coming from the peruvian amazon with PSC associated with Sjögren Syndrome, Chronic Pancreatitis and Retroperitoneal Fibrosis, without colonic involvement. She was treated with external biliary drainage and controlled for 12 months. In this paper, clinical, biochemical, radiological, histological and therapeutic features are reviewed as well as its possible immunologie autoimmune origin.

Gain of Function Mutations of PIK3CD as a Cause of Primary Sclerosing Cholangitis.

PubMed

Hartman, Heather N; Niemela, Julie; Hintermeyer, Mary K; Garofalo, Mary; Stoddard, Jennifer; Verbsky, James W; Rosenzweig, Sergio D; Routes, John M

2015-01-01

Gain of function (GOF) mutation in the p110δ catalytic subunit of the phosphatidylinositol-3-OH kinase (PIK3CD) is the cause of a primary immunodeficiency (PID) characterized by recurrent sinopulmonary infections and lymphoproliferation. We describe a family of two adults and three children with GOF mutation in PIK3CD, all with recurrent sinopulmonary infections and varied infectious and non-infectious complications. The two adults have Primary Sclerosing Cholangitis (PSC) without evidence of Cryptosporidium parvum infection and have required liver transplantation. PSC is a novel phenotype of GOF mutation in PIK3CD.

Liquid and Foam Sclerotherapy for Spider and Varicose Veins.

PubMed

Gibson, Kathleen; Gunderson, Krissa

2018-04-01

Sclerotherapy has wide applicability in treating venous disease at every stage of clinical disease. The various sclerosant drugs and formulations each have unique properties, utilities, and side effects. Treating physicians should be aware of the differences between agents, accounting for disease presentation, vein characteristics, and patient comorbidities when selecting the appropriate sclerosing agents. Successful outcomes rely on proper patient evaluation and assessment for contraindications to sclerotherapy. Thorough patient education regarding realistic expectations with sclerotherapy in terms of symptoms relief, recurrence, and improvement in appearance is of chief importance. Copyright © 2017 Elsevier Inc. All rights reserved.

Catatonia as presenting clinical feature of subacute sclerosing panencephalitis

PubMed Central

Dayal, Prabhoo; Balhara, Yatan Pal Singh

2014-01-01

Catatonia is not a usual clinical presentation of subacute sclerosing panencephalitis (SSPE), especially in the initial stages of illness. However, there is only one reported case of SSPE presenting as catatonia among children. In this report, however, there were SSPE-specific changes on EEG and the catatonia failed to respond to lorazepam. We describe a case of SSPE in a child presenting as catatonia that presented with clinical features of catatonia and did not have typical EEG findings when assessed at first contact. He responded to lorazepam and EEG changes emerged during the course of follow-up. PMID:24891908

Subacute sclerosing panencephalitis presenting as rapidly progressive young-onset dementia.

PubMed

Chakor, Rahul Tryambak; Santosh, Nandanavana Subbareddy

2013-07-01

Onset of dementia before 65 years of age is termed as young-onset dementia (YOD). Very little literature exists regarding the clinical features and diagnoses of dementia in younger individuals. We present a case series of four patients of age 10 to 23 years with severe dementia within 18 months of clinical onset (rapidly progressive dementia). Three patients had generalised periodic complexes typical of subacute sclerosing panencephalitis (SSPE) on electroencephalogram (EEG). All patients had elevated cerebrospinal fluid (CSF) IgG measles antibodies. Our case series highlights that SSPE is an important cause of rapidly progressive YOD in developing countries like India.

Maternal smoking during pregnancy is associated with childhood bone fractures in offspring - A birth-cohort study of 6718 children.

PubMed

Parviainen, Roope; Auvinen, Juha; Pokka, Tytti; Serlo, Willy; Sinikumpu, Juha-Jaakko

2017-08-01

In children there is limited understanding about the biological and environmental risk factors of fractures. Therefore, we aimed to study the effect of maternal smoking on preschool children's fractures hypothesizing that the fracture risk might be programmed during intrauterine growth in means of disturbed bone formation. A prospective birth cohort included women living in Northern Finland with an expected date of delivery between July 1st, 1985 and June 30th, 1986 (N=9362), and their offspring (N=9432). Smoking was inquired during pregnancy and when the offspring reached seven years of age. Information on in-hospital-treated fractures among the children was collected from the National Hospital Discharge Register (NHDR). The cases who declined to participate or suffered from any bone dysplasia such as osteogenesis imperfecta or any malignancy were excluded, thus 6718 subjects (71.2%) were finally included. Poisson regression analysis with adjustment for gender, asthma, rheumatoid arthritis, socioeconomic status of the family, maternal age and body mass index (BMI) of the children was used to determine the association between maternal smoking during pregnancy and bone fractures. Maternal smoking during pregnancy was associated with a 1.83-fold (95% CI 1.06-3.02, p=0.022) increased risk of in-hospital-treated fractures at pre-school age. The fracture risk in childhood is perhaps increased as a result of modified bone development of the fetus due to maternal smoking. Copyright © 2017 Elsevier Inc. All rights reserved.

Malignant transformation of oral epithelial dysplasia: clinicopathological risk factors and outcome analysis in a retrospective cohort of 138 cases.

PubMed

Liu, Wei; Bao, Zhe-Xuan; Shi, Lin-Jun; Tang, Guo-Yao; Zhou, Zeng-Tong

2011-10-01

To explore the usefulness of a new binary system of grading dysplasia proposed by the World Health Organization and to identify significant risk factors for malignant transformation in a long-term follow-up cohort of patients with oral epithelial dysplasia. A total of 138 patients with histologically confirmed oral dysplasia between 1978 and 2008 were reviewed retrospectively in our department. The mean follow-up period was 5.1 years. Of these dysplasias, 37 (26.8%) developed into cancer, with a mean duration of 4.6 years. Cox regression analysis revealed that high-grade dysplasia was an independent risk factor for transition, but age, gender, lesion site, diet habit, smoking and alcohol intake were not risk factors. High-grade dysplasia was associated with a 2.78-fold (95% confidence interval 1.44-5.38; P = 0.002) increased risk of transition, as compared with low-grade dysplasia. Consistently, high-grade dysplasia had a significantly higher incidence of malignancy than low-grade dysplasia by Kaplan-Meier analysis (log-rank test, P = 0.001). The utilization of high-grade dysplasia as a significant indicator for evaluating malignant transformation risk in patients with potentially malignant lesions is suggested; this may be helpful to guide treatment selection in clinical practice. 2011 Blackwell Publishing Limited.

18F-NaF PET/CT in Extensive Melorheostosis of the Axial and Appendicular Skeleton With Soft-Tissue Involvement.

PubMed

Papadakis, Georgios Z; Jha, Smita; Bhattacharyya, Timothy; Millo, Corina; Tu, Tsang-Wei; Bagci, Ulas; Marias, Kostas; Karantanas, Apostolos H; Patronas, Nicholas J

2017-07-01

Melorheostosis is a rare, nonhereditary, benign, sclerotic bone dysplasia with no sex predilection, typically occurring in late childhood or early adulthood, which can lead to substantial functional morbidity, depending on the sites of involvement. We report on a patient with extensive melorheostosis in the axial and appendicular skeleton, as well as in the soft tissues, who was evaluated with whole-body F-NaF PET/CT scan. All melorheostotic lesions of the skeleton and of the ossified soft-tissue masses demonstrated intensely increased F-NaF activity, suggesting the application of this modality in assessing and monitoring the disease activity.

Report of Two Siblings with Overlapping Features of Ellis-van Creveld and Weyers Acrodental Dysostosis

PubMed Central

Shetty, Devi C.; Singh, Harkanwal P.; Kumar, Prince; Verma, Chanchal

2012-01-01

Skeletal dysplasias are a heterogenous group of disorders combining abnormalities in the skull and other skeletal bones. Weyers acrofacial dysostosis also known as Weyers acrodental dysostosis was first described in 1952, by Weyers, as a postaxial polydactyly, which had features distinct from, yet some in common with the Ellis-van Creveld Syndrome (EvC). Both the syndromes have been mapped to the same chromosome, 4p16. The cases reported here highlight the overlapping features of both syndromes, which are dissimilar in mode of inheritance and phenotypic severity, emphasizing the need for genetic analysis, to categorize these conditions. PMID:22616035

A Cross-sectional Multicenter Study of Osteogenesis Imperfecta in North America – Results from the Linked Clinical Research Centers

PubMed Central

Patel, Ronak M; Nagamani, Sandesh CS; Cuthbertson, David; Campeau, Philippe M; Krischer, Jeffrey P; Shapiro, Jay R; Steiner, Robert D; Smith, Peter A; Bober, Michael B; Byers, Peter H; Pepin, Melanie; Durigova, Michaela; Glorieux, Francis H; Rauch, Frank; Lee, Brendan H; Smith, Tracy; Sutton, V. Reid

2017-01-01

Osteogenesis Imperfecta (OI) is the most common skeletal dysplasia that predisposes to recurrent fractures and bone deformities. In spite of significant advances in understanding the genetic basis of OI, there have been no large-scale natural history studies. To better understand the natural history and improve the care of patients, a network of Linked Clinical Research Centers (LCRC) was established. Subjects with OI were enrolled in a longitudinal study, and in this report, we present cross-sectional data on the largest cohort of OI subjects (n=544). OI type III subjects had higher prevalence of dentinogenesis imperfecta, severe scoliosis, and long bone deformities as compared to those with OI types I and IV. Whereas the mean LS aBMD was low across all OI subtypes, those with more severe forms had lower bone mass. Molecular testing may help predict the subtype in type I collagen-related OI. Analysis of such well-collected and unbiased data in OI can not only help answer questions that are relevant to patient care but also foster hypothesis-driven research, especially in the context of “phenotypic expansion” driven by next-generation sequencing. PMID:24754836

A case of McCune-Albright syndrome associated with pituitary GH adenoma: therapeutic process and autopsy.

PubMed

Liu, Fuyi; Li, Wenting; Yao, Yong; Li, Guilin; Yang, Yi; Dou, Wanchen; Zhong, Dingrong; Wang, Lin; Zhu, Xiangdong; Hu, Hua; Zhang, Jianmin; Wang, Renzhi; Chen, Gao

2011-01-01

McCune-Albright syndrome (MAS) is a clinical syndrome with low incidence, and its concurrence with pituitary GH adenoma is rare. Little of the history, treatment and outcome has been studied. Follow-up of a 37-year-old male patient of MAS associated with pituitary GH adenoma was performed continuously recording the disease development and the treatment process until death, after which an autopsy was performed. Radiation therapy (RT) efficaciously controlled GH hypersecretion, however, it may have been the cause of the malignant transformation of the dysplastic bone tissue, which eventually caused brain hernia and death; autopsy demonstrated that the cranium had significant thickening (as much as 10 cm), the pathological diagnosis was fibrous dysplasia of bone associated with chondrosarcoma; and undifferentiated chondrosarcoma with malignant fibrous histocytoma subtype in the sellar region; nodular goiter with the thyroid gland, one nodus was pathologically demonstrated as papillary carcinoma. GH adenoma, present in a patient with MAS, might be cured by RT; but the risk of malignant transformation of the dysplastic bone tissue in the field of irradiation make it controversial. Lessons from the case reported here told us that we should take great caution when recommending RT for patients like this.

A cell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization

PubMed Central

Khavandgar, Zohreh; Poirier, Christophe; Clarke, Christopher J.; Li, Jingjing; Wang, Nicholas; McKee, Marc D.; Hannun, Yusuf A.

2011-01-01

A deletion mutation called fro (fragilitas ossium) in the murine Smpd3 (sphingomyelin phosphodiesterase 3) gene leads to a severe skeletal dysplasia. Smpd3 encodes a neutral sphingomyelinase (nSMase2), which cleaves sphingomyelin to generate bioactive lipid metabolites. We examined endochondral ossification in embryonic day 15.5 fro/fro mouse embryos and observed impaired apoptosis of hypertrophic chondrocytes and severely undermineralized cortical bones in the developing skeleton. In a recent study, it was suggested that nSMase2 activity in the brain regulates skeletal development through endocrine factors. However, we detected Smpd3 expression in both embryonic and postnatal skeletal tissues in wild-type mice. To investigate whether nSMase2 plays a cell-autonomous role in these tissues, we examined the in vitro mineralization properties of fro/fro osteoblast cultures. fro/fro cultures mineralized less than the control osteoblast cultures. We next generated fro/fro;Col1a1-Smpd3 mice, in which osteoblast-specific expression of Smpd3 corrected the bone abnormalities observed in fro/fro embryos without affecting the cartilage phenotype. Our data suggest tissue-specific roles for nSMase2 in skeletal tissues. PMID:21788370

A combined procedure with Bereiter-type trochleoplasty leads to a stable patellofemoral joint at 5-year follow-up.

PubMed

Wind, Rutger J P; Heesterbeek, Petra J C; Wymenga, Ate B

2018-06-11

Trochlear dysplasia is a major risk factor predisposing to patellar instability and has been reported to occur in up to 85% of patients with recurrent patellar dislocation. Different operative techniques have been described to correct trochlear dysplasia, including the Bereiter technique, in which subchondral bone is removed and the cartilage can be compressed into a U-shaped groove. The hypothesis was that after a Bereiter-type trochleoplasty combined with medialisation of the tibial tubercle and MPFL reconstruction, patellar pain and instability decreased and anatomic reconstruction can be seen radiographically after 5-year follow-up. Between 2004 and 2011, a combined procedure including Bereiter-type trochleoplasty was performed on 21 consecutively included patients (22 knees) with objective patellar instability and severe trochlear dysplasia. Instability and pain were assessed preoperatively and 3, 6, 12, 24 and 60 months postoperatively with the visual analogue scale (VAS) for pain and instability, Kujala, International Knee Documentation Committee Subjective Knee Evaluation (IKDC SKE) and Short Form Health Survey (SF-36). Pre- and postoperatively, a true lateral radiograph was made to investigate the presence of the crossing sign and to measure the trochlear bump and trochlear depth, as well as a sunrise patella view to measure the sulcus angle. VAS pain and instability, Kujala and IKDC SKE improved significantly 5 years after trochleoplasty (p < 0.05). SF-36 showed no significant improvement. None of the patients reported patellar dislocations postoperatively. Sport activities remained limited. Postoperative radiographs showed no crossing sign. There was a significant increase in trochlear depth (p < 0.0001) and also a significant decrease in trochlear bump and sulcus angle (both p < 0.0001). A combined procedure consisting of Bereiter-type trochleoplasty, medialisation of the tibial tubercle and MPFL reconstruction in patients with objective patellar instability and severe trochlear dysplasia resulted in a clear decrease of pain and instability. Radiological assessment showed anatomical reconstruction. Nevertheless, residual symptoms remain and the possibility of future cartilage damage is uncertain. IV.

Rigid fixation improves outcomes of spinal fusion for C1-C2 instability in children with skeletal dysplasias.

PubMed

Helenius, Ilkka; Crawford, Haemish; Sponseller, Paul D; Odent, Thierry; Bernstein, Robert M; Stans, Anthony A; Hedequist, Daniel; Phillips, Jonathan H

2015-02-04

Upper cervical instability is common in many skeletal dysplasias, and surgical treatment can be difficult because of small, fragile osseous elements. In this study of children with skeletal dysplasia and upper cervical instability, we compared fusion rates and complications between (1) patients treated with no instrumentation or with wiring techniques and (2) those who underwent rigid cervical spine instrumentation. We also sought to characterize the presentation and common parameters of upper cervical instability in this population. A multicenter study identified twenty-eight children with skeletal dysplasia who underwent surgery from 2000 through 2011 for C1-C2 instability and were followed for a minimum of two years. Fourteen children were treated with no instrumentation or with instrumentation with wires or cables (nonrigid-fixation group) and fourteen were treated with screws (or hooks) and rods (rigid-fixation group). All patients received autograft, and twenty (twelve in the nonrigid group and eight in the rigid group) were treated with a halo-body jacket. Fourteen children had C1-C2 fusion, and fourteen had occipitocervical fusion. Eleven (39%) underwent spinal cord decompression. The nonunion rate was significantly higher in the nonrigid-fixation group (six of fourteen) than in the rigid-fixation group (zero of fourteen; p = 0.0057). Complications, including nonunion, occurred in nine patients in the nonrigid group and one patient in the rigid group. However, two of the complications in the nonrigid-fixation group were vertebral artery bleeding episodes that actually occurred during an attempt at rigid fixation (the fixation was subsequently done with wiring). No new neurologic deficits were observed. Five of the seven children with a preoperative neurologic deficit showed at least partial recovery, with significant improvement in the Japanese Orthopaedic Association upper-extremity score (p = 0.047). The nonunion rate is relatively high after patients undergo spinal fusion for C1-C2 instability with nonrigid instrumentation, even if a halo-body jacket is applied. Rigid fixation with screws and rods improves fusion rates. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Incidence of Fanconi anemia in children with congenital thumb anomalies referred for diepoxybutane testing.

PubMed

Webb, Michelle L; Rosen, Heather; Taghinia, Amir; McCarty, Erika R; Cerrato, Felecia; Upton, Joseph; Labow, Brian I

2011-06-01

Fanconi anemia (FA) is a rare genetic disorder of DNA repair that with near uniformity leads to bone marrow failure and resulting morbidity and mortality. Approximately 50% of FA patients are born with anomalies of the thumb or thumb and radius, and it has been recommended that all patients born with thumb anomalies undergo testing. However, the risk of FA in this population is unknown. We determined the incidence of FA in children with congenital thumb anomalies referred for FA testing and characterized those who tested positive. We queried our database for patients who presented with congenital thumb anomalies and who underwent diepoxybutane (DEB) testing for FA between 1999 and 2008 at Children's Hospital Boston and the Dana-Farber Cancer Institute. During this time period, 543 congenital thumb anomaly patients (235 with thumb hypoplasia) presented to our institution. A total of 81 patients with thumb abnormalities underwent DEB testing. Six patients (7% of those tested; 1% of the total; 3% of thumb hypoplasia patients) had a positive DEB test consistent with the diagnosis of FA; all had other non-upper-extremity anomalies associated with FA. Of 6 FA patients, 5 had bilateral involvement; all had some degree of thumb hypoplasia (3 also had radial dysplasia). Mean age at testing was 2.6 years (SD 4.3). Most of the patients tested had multiple physical anomalies (n = 66). The anomaly distribution was: thumb hypoplasia and radial dysplasia (n = 29), thumb hypoplasia (n = 26), radial polydactyly (n = 12), radial polydactyly and radial dysplasia (n = 1), and proximally placed thumb and radial dysplasia (n = 1). Twelve patients had other thumb anomalies. Although the incidence of FA in patients with thumb anomalies may be low, patients with thumb hypoplasia and other physical findings associated with FA, specifically café au lait spots and short stature, appear to have an increased risk of FA. Because hand surgeons see these patients early in life, they have the opportunity to refer these patients for FA testing to initiate early education, family genetic counseling, and treatment if warranted. Prognostic IV. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Follistatin in chondrocytes: the link between TRPV4 channelopathies and skeletal malformations

PubMed Central

Leddy, Holly A.; McNulty, Amy L.; Lee, Suk Hee; Rothfusz, Nicole E.; Gloss, Bernd; Kirby, Margaret L.; Hutson, Mary R.; Cohn, Daniel H.; Guilak, Farshid; Liedtke, Wolfgang

2014-01-01

Point mutations in the calcium-permeable TRPV4 ion channel have been identified as the cause of autosomal-dominant human motor neuropathies, arthropathies, and skeletal malformations of varying severity. The objective of this study was to determine the mechanism by which TRPV4 channelopathy mutations cause skeletal dysplasia. The human TRPV4V620I channelopathy mutation was transfected into primary porcine chondrocytes and caused significant (2.6-fold) up-regulation of follistatin (FST) expression levels. Pore altering mutations that prevent calcium influx through the channel prevented significant FST up-regulation (1.1-fold). We generated a mouse model of theTRPV4V620I mutation, and found significant skeletal deformities (e.g., shortening of tibiae and digits, similar to the human disease brachyolmia) and increases in Fst/TRPV4 mRNA levels (2.8-fold). FST was significantly up-regulated in primary chondrocytes transfected with 3 different dysplasia-causing TRPV4 mutations (2- to 2.3-fold), but was not affected by an arthropathy mutation (1.1-fold). Furthermore, FST-loaded microbeads decreased bone ossification in developing chick femora (6%) and tibiae (11%). FST gene and protein levels were also increased 4-fold in human chondrocytes from an individual natively expressing the TRPV4T89I mutation. Taken together, these data strongly support that up-regulation of FST in chondrocytes by skeletal dysplasia-inducing TRPV4 mutations contributes to disease pathogenesis.—Leddy, H. A., McNulty, A. L., Lee, S. H., Rothfusz, N. E., Gloss, B., Kirby, M. L., Hutson, M. R., Cohn, D. H., Guilak, F., Liedtke, W. Follistatin in chondrocytes: the link between TRPV4 channelopathies and skeletal malformations. PMID:24577120

Uncommon runs of homozygosity disclose homozygous missense mutations in two ciliopathy-related genes (SPAG17 and WDR35) in a patient with multiple brain and skeletal anomalies.

PubMed

Córdova-Fletes, Carlos; Becerra-Solano, Luis E; Rangel-Sosa, Martha M; Rivas-Estilla, Ana María; Alberto Galán-Huerta, Kame; Ortiz-López, Rocío; Rojas-Martínez, Augusto; Juárez-Vázquez, Clara I; García-Ortiz, José E

2018-03-01

We describe a patient severely affected with multiple congenital anomalies, including brain malformations and skeletal dysplasia suggestive of cranioectodermal dysplasia (CED) ciliopathy, who unusually carries several homozygosity tracts involving homozygous missense mutations in SPAG17 (exon 8; c.1069G > C; p.Asp357His) and WDR35 (exon 13; c.1415G > A; p.Arg472Gln) as revealed by homozygosity mapping and next generation sequencing. SPAG17 is essential for the function and structure of motile cilia, while WDR35 belongs to the same intraflagellar transport (IFT) gene family whose protein products are part of functional IFT A and B complexes. Formerly, SPAG17 was related - through polymorphic variants - to an influence on individuals' height; more recently, Spag17-/- mice models were reported to present skeletal and bone defects, reduced mucociliary clearance, respiratory distress, and cerebral ventricular enlargement. Homozygous or compound heterozygous mutations in WDR35 have mainly been related to CED2 or short-rib thoracic dysplasia 7, with only three cases showing some brain anomalies. Given that our patient presents these clinical features and the close functional relationship between SPAG17 and WDR35, it is feasible that the combined effects from both mutations contribute to his phenotype. To our knowledge, this patient is the first to harbor a likely pathogenic homozygous mutation in both genes at the same time. Thus, the resulting complex phenotype of this patient illustrates the heterogeneity associated with ciliopathies and further expands the clinical and mutational spectrum of these diseases. Finally, we highlight the combined use of high-throughput tools to diagnose and support the proper handling of this and other patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Alterations in gene expression and DNA methylation during murine and human lung alveolar septation.

PubMed

Cuna, Alain; Halloran, Brian; Faye-Petersen, Ona; Kelly, David; Crossman, David K; Cui, Xiangqin; Pandit, Kusum; Kaminski, Naftali; Bhattacharya, Soumyaroop; Ahmad, Ausaf; Mariani, Thomas J; Ambalavanan, Namasivayam

2015-07-01

DNA methylation, a major epigenetic mechanism, may regulate coordinated expression of multiple genes at specific time points during alveolar septation in lung development. The objective of this study was to identify genes regulated by methylation during normal septation in mice and during disordered septation in bronchopulmonary dysplasia. In mice, newborn lungs (preseptation) and adult lungs (postseptation) were evaluated by microarray analysis of gene expression and immunoprecipitation of methylated DNA followed by sequencing (MeDIP-Seq). In humans, microarray gene expression data were integrated with genome-wide DNA methylation data from bronchopulmonary dysplasia versus preterm and term lung. Genes with reciprocal changes in expression and methylation, suggesting regulation by DNA methylation, were identified. In mice, 95 genes with inverse correlation between expression and methylation during normal septation were identified. In addition to genes known to be important in lung development (Wnt signaling, Angpt2, Sox9, etc.) and its extracellular matrix (Tnc, Eln, etc.), genes involved with immune and antioxidant defense (Stat4, Sod3, Prdx6, etc.) were also observed. In humans, 23 genes were differentially methylated with reciprocal changes in expression in bronchopulmonary dysplasia compared with preterm or term lung. Genes of interest included those involved with detoxifying enzymes (Gstm3) and transforming growth factor-β signaling (bone morphogenetic protein 7 [Bmp7]). In terms of overlap, 20 genes and three pathways methylated during mouse lung development also demonstrated changes in methylation between preterm and term human lung. Changes in methylation correspond to altered expression of a number of genes associated with lung development, suggesting that DNA methylation of these genes may regulate normal and abnormal alveolar septation.

Hypohidrotic and hidrotic ectodermal dysplasia: a report of two cases.

PubMed

Vasconcelos Carvalho, Marianne; Romero Souto de Sousa, José; Paiva Correa de Melo, Filipe; Fonseca Faro, Tatiane; Nunes Santos, Ana Clara; Carvalho, Silvia; Veras Sobral, Ana Paula

2013-07-14

Ectodermal dysplasias are a large group of syndromes characterized by anomalies in the structures of ectodermal origin. There are 2 major types of this disorder, based on clinical findings: hypohidrotic ectodermal dysplasia and hidrotic ectodermal dysplasia. This clinical classification is very important because clinical professionals involved with this disease need first a clear and practical method of diagnosis. The main oral manifestation of ectodermal dysplasia may be expressed as hypodontia. Thus, dental professionals may be the first to diagnose ectodermal dysplasia. The present article reports one case of each of the main types (hypohidrotic and hidrotic) of ectodermal dysplasia and the authors review the literature regarding the pathogenesis, clinical features, and therapeutic management of this condition.

Cranioplasty Using a Modified Split Calvarial Graft Technique in Cleidocranial Dysplasia

PubMed Central

Jung, Young Taek; Cho, Jae Ik

2015-01-01

Cleidocranial dysplasia is a well-documented rare autosomal dominant skeletal dysplasia characterized by hypoplastic/aplastic clavicles, brachycephalic skull, patent sutures and fontanelles, midface hypoplasia, and abnormalities of dentition. Patients with cleidocranial dysplasia often complain about undesirable esthetic appearance of their forehead and skull. Notwithstanding many studies of molecular, genetics and skeletal abnormalities of this congenial disorder, there have been very few written reports of cranioplasty involving cleidocranial dysplasia. Thus, we report a rare case of successful cranioplasty using a modified split calvarial graft technique in patient with cleidocranial dysplasia. PMID:26279819

Sessile serrated adenomas with dysplasia: morphological patterns and correlations with MLH1 immunohistochemistry.

PubMed

Liu, Cheng; Walker, Neal I; Leggett, Barbara A; Whitehall, Vicki Lj; Bettington, Mark L; Rosty, Christophe

2017-12-01

Sessile serrated adenomas are the precursor polyp of approximately 20% of colorectal carcinomas. Sessile serrated adenomas with dysplasia are rarely encountered and represent an intermediate step to malignant progression, frequently associated with loss of MLH1 expression. Accurate diagnosis of these lesions is important to facilitate appropriate surveillance, particularly because progression from dysplasia to carcinoma can be rapid. The current World Health Organization classification describes two main patterns of dysplasia occurring in sessile serrated adenomas, namely, serrated and conventional. However, this may not adequately reflect the spectrum of changes seen by pathologists in routine practice. Furthermore, subtle patterns of dysplasia that are nevertheless associated with loss of MLH1 expression are not encompassed in this classification. We performed a morphological analysis of 266 sessile serrated adenomas with dysplasia with concurrent MLH1 immunohistochemistry with the aims of better defining the spectrum of dysplasia occurring in these lesions and correlating dysplasia patterns with MLH1 expression. We found that dysplasia can be divided morphologically into four major patterns, comprising minimal deviation (19%), serrated (12%), adenomatous (8%) and not otherwise specified (79%) groups. Minimal deviation dysplasia is defined by minor architectural and cytological changes that typically requires loss of MLH1 immunohistochemical expression to support the diagnosis. Serrated dysplasia and adenomatous dysplasia have distinctive histological features and are less frequently associated with loss of MLH1 expression (13 and 5%, respectively). Finally, dysplasia not otherwise specified encompasses most cases and shows a diverse range of morphological changes that do not fall into the other subgroups and are frequently associated with loss of MLH1 expression (83%). This morphological classification of sessile serrated adenomas with dysplasia may represent an improvement on the current description as it correlates with the underlying mismatch repair protein status of the polyps and better highlights the range of morphologies seen by pathologists.

Autoimmune hepatitis/sclerosing cholangitis overlap syndrome in childhood: a 16-year prospective study.

PubMed

Gregorio, G V; Portmann, B; Karani, J; Harrison, P; Donaldson, P T; Vergani, D; Mieli-Vergani, G

2001-03-01

To investigate whether sclerosing cholangitis with an autoimmune serology characteristic of autoimmune hepatitis (AIH) and AIH are distinct entities, we studied 55 consecutive children with clinical and/or biochemical evidence of liver disease and circulating antinuclear (ANA), anti-smooth muscle (SMA), and/or liver-kidney-microsomal type 1 (LKM1) autoantibodies. They underwent liver biopsy, direct cholangiography, sigmoidoscopy, and rectal biopsy at presentation. Twenty-eight were diagnosed as AIH in the absence and 27 autoimmune sclerosing cholangitis (ASC) in the presence of radiological features of cholangiopathy. Twenty-six ASC and 20 AIH had ANA and/or SMA; 1 ASC and 8 AIH LKM1 autoantibody. Similarities between the 2 conditions included most clinical and biochemical parameters and a lower frequency of HLA DR4. Inflammatory bowel disease and histological biliary changes were more common in ASC; coagulopathy, hypoalbuminemia, lymphocytic periportal hepatitis, and HLA DR3 were more common in AIH. Histological biliary changes were observed in 65% of ASC and 31% of AIH patients. Eighty-nine percent responded to immunosuppression. Follow-up liver biopsies from 17 ASC and 18 AIH patients had similarly reduced inflammatory activity and no progression to cirrhosis. Sixteen follow-up cholangiograms from AIH patients and 9 from ASC patients were unchanged, while 8 ASC patients showed a progressive cholangiopathy. One child with AIH and ulcerative colitis developed sclerosing cholangitis 8 years after presentation. At 2 to 16 years (median, 7 years) from presentation, all patients are alive, including 4 ASC patients who underwent liver transplantation. In conclusion, ASC and AIH are similarly prevalent in childhood; cholangiography is often needed to distinguish between these 2 entities, which are likely to lie within the same disease process.

Autoimmune liver serology: current diagnostic and clinical challenges.

PubMed

Bogdanos, Dimitrios-P; Invernizzi, Pietro; Mackay, Ian-R; Vergani, Diego

2008-06-07

Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases (AiLD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis variants in adults and children. AIH-1 is specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1). SMA, ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation. PBC is specified by antimitochondrial antibodies (AMA) reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants, first the classical primary sclerosing cholangitis (PSC) mostly affecting adult men wherein the only (and non-specific) reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA), also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with serological features resembling those of type 1 AIH. Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens, and automated technologies such as ELISAs and bead assays, become available to complement (or even compete with) traditional immunofluorescence procedures. We survey for the first time global trends in quality assurance impacting as it does on (1) manufacturers/purveyors of kits and reagents, (2) diagnostic service laboratories that fulfill clinicians' requirements, and (3) the end-user, the physician providing patient care, who must properly interpret test results in the overall clinical context.

Autoimmune liver serology: Current diagnostic and clinical challenges

PubMed Central

Bogdanos, Dimitrios P; Invernizzi, Pietro; Mackay, Ian R; Vergani, Diego

2008-01-01

Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases (AiLD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis variants in adults and children. AIH-1 is specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1). SMA, ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation. PBC is specified by antimitochondrial antibodies (AMA) reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants, first the classical primary sclerosing cholangitis (PSC) mostly affecting adult men wherein the only (and non-specific) reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA), also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with serological features resembling those of type 1 AIH. Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens, and automated technologies such as ELISAs and bead assays, become available to complement (or even compete with) traditional immunofluorescence procedures. We survey for the first time global trends in quality assurance impacting as it does on (1) manufacturers/purveyors of kits and reagents, (2) diagnostic service laboratories that fulfill clinicians’ requirements, and (3) the end-user, the physician providing patient care, who must properly interpret test results in the overall clinical context. PMID:18528935

Prophylaxis of post-ERC infectious complications in patients with biliary obstruction by adding antimicrobial agents into ERC contrast media- a single center retrospective study.

PubMed

Wobser, Hella; Gunesch, Agnetha; Klebl, Frank

2017-01-13

Patients with biliary obstruction are at high risk to develop septic complications after endoscopic retrograde cholangiography (ERC). We evaluated the benefits of local application of antimicrobial agents into ERC contrast media in preventing post-ERC infectious complications in a high-risk study population. Patients undergoing ERC at our tertiary referral center were retrospectively included. Addition of vancomycin, gentamicin and fluconazol into ERC contrast media was evaluated in a case-control design. Outcomes comprised infectious complications within 3 days after ERC. In total, 84 ERC cases were analyzed. Primarily indications for ERC were sclerosing cholangitis (75%) and malignant stenosis (9.5%). Microbial testing of collected bile fluid in the treatment group was positive in 91.4%. Detected organisms were sensitive to the administered antimicrobials in 93%. The use of antimicrobials in contrast media was associated with a significant decrease in post-ERC infectious complications compared to non-use (14.3% vs. 33.3%; odds ratio [OR]: 0.33, 95% confidence interval [CI]: 0.114-0.978). After adjusting for the variables acute cholangitis prior to ERC and incomplete biliary drainage, the beneficial effect of intraductal antibiotic prophylaxis was even more evident (OR = 0.153; 95% CI: 0.039-0.598, p = 0.007). Patients profiting most obviously from intraductal antimicrobials were those with secondary sclerosing cholangitis. Local application of a combination of antibiotic and antimycotic agents to ERC contrast media efficiently reduced post-ERC infectious events in patients with biliary obstruction. This is the first study that evaluates ERC-related infectious complications in patients with secondary sclerosing cholangitis. Our first clinical results should now be prospectively evaluated in a larger patient cohort to improve the safety of ERC, especially in patients with secondary sclerosing cholangitis.

Long-term clinical and radiographic outcome of the PPF system in ceramic-on-polyethylene hip bearings.

PubMed

Legenstein, R; Huber, W; Ungersboeck, A; Boesch, P

2006-01-01

From 1990 to 1991 we implanted 176 non-cemented proximal press-fit (PPF) total hip arthroplasties (THA) with ceramic-on-polyethylene articulation in 170 patients. Of these, 119 patients (122 THA) were followed from 104 to 129 months. Four cups have been revised for aseptic loosening, but revealed no radiolucencies of the stem. Two infections and two dislocations occurred. The median postoperative Harris hip score was 91. Ninety-eight per cent of the patients were satisfied with the outcome, 83% were free of pain and 67% walked without a limp. Serial radiographs showed stable fixation with bone ongrowth in nearly all arthroplasties except for four cups. Stem radiolucencies were first seen within 12 months, but were of no clinical relevance. Proximal periprosthetic bone resorption of the stem was seen in 18%. Radiolucencies occurred because of polyethylene debris-induced granulomas. The PPF system yields satisfactory long-term results in patients with primary and secondary hip osteoarthritis and dysplasia.

Bone marrow VEGFC expression is associated with multilineage dysplasia and several prognostic markers in adult acute myeloid leukemia, but not with survival.

PubMed

Guillem, Vicent; Calabuig, Marisa; Brunet, Salut; Esteve, Jordi; Escoda, Lourdes; Gallardo, David; Ribera, Josep-Maria; Queipo de Llano, María Paz; Arnan, Montserrat; Pedro, Carme; Amigo, María Luz; Martí-Tutusaus, Josep M; García-Guiñón, Antoni; Bargay, Joan; Sampol, Antonia; Salamero, Olga; Font, Llorenç; Talarn, Carme; Hoyos, Montserrat; Díaz-Beyá, Marina; Garrido, Ana; Navarro, Blanca; Nomdédeu, Josep; Sierra, Jordi; Tormo, Mar

2018-01-18

Vascular endothelial growth factor C (VEGFC) stimulates leukemia cell proliferation and survival, and promotes angiogenesis. We studied VEGFC expression in bone marrow samples from 353 adult acute myeloid leukemia (AML) patients and its relationship with several clinical, cytogenetic, and molecular variables. We also studied the expression of 84 genes involved in VEGF signaling in 24 patients. We found that VEGFC expression was higher in AML patients with myelodysplasia-related changes (AML-MRC) than in patients with non-AML-MRC. We also found an association between VEGFC expression and the patient cytogenetic risk group, with those with a worse prognosis having higher VEGFC expression levels. No correlation was observed between VEGFC expression and survival or complete remission. VEGFC expression strongly correlated with expression of the VEGF receptors FLT1, KDR, and NRP1. Thus, in this series, VEGFC expression was increased in AML-MRC and in subgroups with a poorer prognosis, but has no impact on survival.

Small is challenging; distal femur fracture management in an elderly lady with achondroplastic dwarfism.

PubMed

Murphy, Colin G; Chrea, Bopha; Molloy, Alan P; Nicholson, Paul

2013-03-20

Achondroplasia is an autosomal dominant dwarfing condition that represents the most common form of skeletal dysplasia. The disease is caused by a mutation in the gene encoding fibroblast growth factor receptor 3 (FGFR3) found at the p16.3 locus on chromosome 4 which results in severe inhibition of subchondral bone growth. Anatomic variations, including articular and periarticular deformities classically seen with this condition, amplify the complexity of fracture fixation. Blood volume loss, age-related bone fragility, component selection and positioning pose serious orthopaedic challenges. Concomitant cardiovascular, respiratory and neurological comorbidities pose additional high-risk perioperative considerations. Despite an estimated prevalence of 1:25 000 in the general population, there is little literature concerning the operative and postoperative treatment challenges faced by orthopaedic surgeons dealing with fracture management on a patient with this condition. We present a case of an intercondylar femoral fracture in an elderly achondroplastic lady successfully treated with percutaneous screw fixation.

Craniofacial Manifestations of Systemic Disorders: CT and MR Imaging Findings and Imaging Approach.

PubMed

Andreu-Arasa, V Carlota; Chapman, Margaret N; Kuno, Hirofumi; Fujita, Akifumi; Sakai, Osamu

2018-01-01

Many systemic diseases or conditions can affect the maxillofacial bones; however, they are often overlooked or incidentally found at routine brain or head and neck imaging performed for other reasons. Early identification of some conditions may significantly affect patient care and alter outcomes. Early recognition of nonneoplastic hematologic disorders, such as thalassemia and sickle cell disease, may help initiate earlier treatment and prevent serious complications. The management of neoplastic diseases such as lymphoma, leukemia, or Langerhans cell histiocytosis may be different if diagnosed early, and metastases to the maxillofacial bones may be the first manifestation of an otherwise occult neoplasm. Endocrinologic and metabolic disorders also may manifest with maxillofacial conditions. Earlier recognition of osteoporosis may alter treatment and prevent complications such as insufficiency fractures, and identification of acromegaly may lead to surgical treatment if there is an underlying growth hormone-producing adenoma. Bone dysplasias sometimes are associated with skull base foraminal narrowing and subsequent involvement of the cranial nerves. Inflammatory processes such as rheumatoid arthritis and sarcoidosis may affect the maxillofacial bones, skull base, and temporomandibular joints. Radiologists should be familiar with the maxillofacial computed tomographic and magnetic resonance imaging findings of common systemic disorders because these may be the first manifestations of an otherwise unrevealed systemic process with potential for serious complications. Online supplemental material is available for this article. © RSNA, 2018.

Severe X-linked chondrodysplasia punctata in nine new female fetuses.

PubMed

Lefebvre, Mathilde; Dufernez, Fabienne; Bruel, Ange-Line; Gonzales, Marie; Aral, Bernard; Saint-Onge, Judith; Gigot, Nadège; Desir, Julie; Daelemans, Caroline; Jossic, Frédérique; Schmitt, Sébastien; Mangione, Raphaele; Pelluard, Fanny; Vincent-Delorme, Catherine; Labaune, Jean-Marc; Bigi, Nicole; D'Olne, Dominique; Delezoide, Anne-Lise; Toutain, Annick; Blesson, Sophie; Cormier-Daire, Valérie; Thevenon, Julien; El Chehadeh, Salima; Masurel-Paulet, Alice; Joyé, Nicole; Vibert-Guigue, Claude; Rigonnot, Luc; Rousseau, Thierry; Vabres, Pierre; Hervé, Philippe; Lamazière, Antonin; Rivière, Jean-Baptiste; Faivre, Laurence; Laurent, Nicole; Thauvin-Robinet, Christel

2015-07-01

Conradi-Hünermann-Happle [X-linked dominant chondrodysplasia punctata 2 (CDPX2)] syndrome is a rare X-linked dominant skeletal dysplasia usually lethal in men while affected women show wide clinical heterogeneity. Different EBP mutations have been reported. Severe female cases have rarely been reported, with only six antenatal presentations. To better characterize the phenotype in female fetuses, we included nine antenatally diagnosed cases of women with EBP mutations. All cases were de novo except for two fetuses with an affected mother and one case of germinal mosaicism. The mean age at diagnosis was 22 weeks of gestation. The ultrasound features mainly included bone abnormalities: shortening (8/9 cases) and bowing of the long bones (5/9), punctuate epiphysis (7/9) and an irregular aspect of the spine (5/9). Postnatal X-rays and examination showed ichthyosis (8/9) and epiphyseal stippling (9/9), with frequent asymmetric short and bowed long bones. The X-inactivation pattern of the familial case revealed skewed X-inactivation in the mildly symptomatic mother and random X-inactivation in the severe fetal case. Differently affected skin samples of the same fetus revealed different patterns of X-inactivation. Prenatal detection of asymmetric shortening and bowing of the long bones and cartilage stippling should raise the possibility of CPDX2 in female fetuses, especially because the majority of such cases involve de novo mutations. © 2015 John Wiley & Sons, Ltd.

Surgical treatment of osteoid osteomas in children and adolescents

NASA Astrophysics Data System (ADS)

Gubina, E. V.; Ryzhikov, D. V.; Podorozhnaya, V. T.; Kirilova, I. A.; Senchenko, E. V.; Sadovoy, M. A.; Fomichev, N. G.; Bondarenko, A. V.; Afanasev, L. M.; Andreev, A. V.; Anastasieva, E. A.

2017-09-01

The article is about on the problems of diagnosis and surgical treatment of osteoid osteomas having various localization in children and adolescents. The results of the treatment of 5 patients (2 boys and 3 girls) aged 4-13 years with osteoid osteomas have been analyzed. In 2 cases, lesions were located in the tibia, in 1 case—femoral neck, in 1 case—ischium (fragment of the acetabulum), in 1 case—vertebra (half-arch). At the clinic, all patients underwent preoperative examination by osteoncologist; there was no disagreement as for the preoperative diagnosis and treatment strategy. In all cases, there was a monostotic lesion and all patients underwent scheduled operations. Scheduled surgery included resection of the "nest" and adjacent sclerotic areas, plastic repair of the post-resection defect was not required. In the case of the periarticular location, we replaced defect the bone defects with allogeneic "straw". This material is widely used in the treatment of bone diseases in children and adolescents: it is free of organic substances, has low immunogenicity, and can be used in the patients with positive allergic history; it is versatile, sterile, has high reparative regeneration activity, and does not require prolongation of postoperative antibiotic therapy or administration of antihistamines. In one patient, an autologous bone from the iliac wing was used. Steel structures have not been used. Microscopic description of preparations: among the reactively sclerosed trabeculae, having compact and coarsely glomerular structure, there is a "nest" consisting of poorly calcified small primitive and osteoid trabeculae, having different stages of cell differentiation with no signs of a typia. Pain relief occurred immediately after surgery, resection accuracy was confirmed by the control MSCT examination. Dynamic follow up time was 2 months to 7 years, recovery was achieved in 100% of cases.

Methylene blue-aided cholangioscopy in patients with biliary strictures: feasibility and outcome analysis.

PubMed

Hoffman, A; Kiesslich, R; Bittinger, F; Galle, P R; Neurath, M F

2008-07-01

Chromoendoscopy using methylene blue is employed in the gastrointestinal tract to delineate neoplastic lesions. We tested the value of chromoendoscopy during choledochoscopy for characterization of local inflammation, neoplasias, and other alterations in patients with biliary strictures. Patients with suspected biliary lesions were scheduled for endoscopic retrograde cholangiography with subsequent cholangioscopy. After initial inspection of the bile duct, 15 ml methylene blue (0.1 %) was administered via the working channel of the cholangioscope. Newly appearing circumscribed or unstained lesions were judged according to their macroscopic type and staining features. Methylene-blue-aided diagnosis was compared with either clinical follow-up of the patients or, in some cases, with the results of targeted biopsies. A total of 55 patients [biliary stenosis/cholestasis of unknown origin (n = 24), stenosis after orthotopic liver transplantation (n = 11), primary sclerosing cholangitis (n = 20)] were included. Methylene blue unmasked subtle mucosal changes and permitted macroscopic characterization of circumscribed lesions. Characteristic surface staining patterns were seen in chronic inflammation, dysplasia, and ischemic-type biliary lesions. Nondysplastic mucosa appeared homogeneously stained, whereas scarred strictures showed a weak uptake of methylene blue. In this prospective feasibility study, methylene-blue-aided cholangioscopy was used for the first time to define different staining patterns of the bile duct. The differences in staining patterns identified normal, dysplastic, and inflamed mucosa of the bile duct, as was proved by follow-up or, in some cases, histology. Whereas homogeneous staining predicted the presence of normal mucosa, absence of staining of circumscribed lesions, or diffused staining of such lesions, represented neoplastic changes or inflammation.

Emerging pharmacologic therapies for primary sclerosing cholangitis.

PubMed

Cheung, Angela C; Lazaridis, Konstantinos N; LaRusso, Nicholas F; Gores, Gregory J

2017-05-01

The only currently approved treatment for primary sclerosing cholangitis (PSC) is liver transplantation, with a median time to transplant of 12-18 years after diagnosis. There are a number of emerging drugs that have the potential to meet this critically unmet need that will be summarized and discussed herein. Although the cause of PSC is unknown, there are a number of novel therapeutics under development. These drugs target presumed pathogenic mechanisms largely extrapolated from ex-vivo and in-vivo preclinical models, as well as translational observations. Future therapeutic strategies for PSC may include a multitude of complex pathogenic mechanisms encompassing pathways of immunomodulation, the microbiome and inflammation-related fibrosis.

Atypical clinical course subacute sclerosing panencephalitis presenting as acute Encephalitis

PubMed Central

Komur, Mustafa; Arslankoylu, Ali E; Okuyaz, Cetin; Kuyucu, Necdet

2012-01-01

We report a 14-year-old boy who presented with loss of consciousness and gait instability. The electroencephalogram (EEG) showed generalized slowing with irregular activity and cerebral magnetic imaging revealed asymmetrical nonspecific signals on basal ganglia. His second electroencephalogram revealed periodical generalized high-voltage slow wave complexes which did not disappear with diazepam induction. Subacute sclerosing panencephalitis (SSPE) was considered and the diagnosis was confirmed with the identification of measles antibodies in cerebrospinal fluid. Our findings show that SSPE should be in mind in the differential diagnosis of meningoencephalitis and acute disseminated encephalomyelitis and highlight the significance of EEG in the diagnosis of unidentified cases. PMID:23248691

Indication of peripheral nerve hyperexcitability in adult-onset subacute sclerosing panencephalitis (SSPE).

PubMed

Schreurs, Annabel; Stålberg, Erik V; Punga, Anna Rostedt

2008-04-01

Subacute sclerosing panencephalitis (SSPE) is a rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection of immune-resistant measles virus. Diagnostic hallmarks include widespread cortical dysfunction on EEG, myoclonus, white matter abnormalities on neuroradiological examination and the presence of IgG anti-measles antibodies in the cerebrospinal fluid. We present the first case of SSPE with signs of peripheral nerve hyperexcitability, observed as extra discharges following the compound motor action potential at motor nerve stimulation. In addition we demonstrate the importance of SSPE in the differential diagnosis of adult patients with psychiatric and neurological symptoms.

A case of feline gastrointestinal eosinophilic sclerosing fibroplasia limited to the mesentery.

PubMed

Kambe, N; Okabe, R; Osada, H; Ogawa, M; Kishimoto, M; Fukushima, R; Kondo, H; Ohmori, K

2018-04-30

An entire, female, mixed-breed cat of unknown age was presented with a 6-week history of lethargy, anorexia and vomiting. There was an increase in the number of white blood cells in the blood, including neutrophils and eosinophils; moderate anaemia; ascites; and possible mesenteric peritonitis. Exploratory laparotomy revealed firm, multifocal small nodules in the mesentery. As the nodules were surgically unresectable, they were biopsied. Histologically, the nodules were composed of thin trabeculae of dense collagen fibres mixed with plump fibroblasts and numerous eosinophils, consistent with feline gastrointestinal eosinophilic sclerosing fibroplasia. Bacteria were not detected on histological examination of the nodules and cytology of the ascites. Remission of disease occurred following treatment with prednisolone and ciclosporin A for 22 days and antibiotics for 40 days. After remission, ciclosporin A was administered for 236 days and then discontinued. Eosinophilia also resolved after treatment with ciclosporin A. The cat is still alive and in good condition on day 689. This report describes what may be an atypical case of feline gastrointestinal eosinophilic sclerosing fibroplasia, lacking involvement of the gastrointestinal tract, and was apparently cured by treatment that involved ciclosporin A. © 2018 British Small Animal Veterinary Association.

Chitosan-doxycycline hydrogel: An MMP inhibitor/sclerosing embolizing agent as a new approach to endoleak prevention and treatment after endovascular aneurysm repair.

PubMed

Zehtabi, Fatemeh; Ispas-Szabo, Pompilia; Djerir, Djahida; Sivakumaran, Lojan; Annabi, Borhane; Soulez, Gilles; Mateescu, Mircea Alexandru; Lerouge, Sophie

2017-12-01

The success of endovascular repair of abdominal aortic aneurysms remains limited due to the development of endoleaks. Sac embolization has been proposed to manage endoleaks, but current embolizing materials are associated with frequent recurrence. An injectable agent that combines vascular occlusion and sclerosing properties has demonstrated promise for the treatment of endoleaks. Moreover, the inhibition of aneurysmal wall degradation via matrix metalloproteinases (MMPs) may further prevent aneurysm progression. Thus, an embolization agent that promotes occlusion, MMP inhibition and endothelial ablation was hypothesized to provide a multi-faceted approach for endoleak treatment. In this study, an injectable, occlusive chitosan (CH) hydrogel containing doxycycline (DOX)-a sclerosant and MMP inhibitor-was developed. Several CH-DOX hydrogel formulations were characterized for their mechanical and sclerosing properties, injectability, DOX release rate, and MMP inhibition. An optimized formulation was assessed for its short-term ability to occlude blood vessels in vivo. All formulations were injectable and gelled rapidly at body temperature. Only hydrogels prepared with 0.075M sodium bicarbonate and 0.08M phosphate buffer as the gelling agent presented sufficient mechanical properties to immediately impede physiological flow. DOX release from this gel was in a two-stage pattern: a burst release followed by a slow continuous release. Released DOX was bioactive and able to inhibit MMP-2 activity in human glioblastoma cells. Preliminary in vivo testing in pig renal arteries showed immediate and delayed embolization success of 96% and 86%, respectively. Altogether, CH-DOX hydrogels appear to be promising new multifunctional embolic agents for the treatment of endoleaks. An injectable embolizing chitosan hydrogel releasing doxycycline (DOX) was developed as the first multi-faceted approach for the occlusion of blood vessels. It combines occlusive properties with DOX sclerosing and MMP inhibition properties, respectively known to prevent recanalization process and to counteract the underlying pathophysiology of vessel wall degradation and aneurysm progression. After drug release, the biocompatible scaffold can be invaded by cells and slowly degrade. Local DOX delivery requires lower drug amount and decreases risks of side effects compared to systemic administration. This new gel could be used for the prevention or treatment of endoleaks after endovascular aneurysm repair, but also for the embolization of other blood vessels such as venous or vascular malformations. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Acute erythroid neoplastic proliferations. A biological study based on 62 patients.

PubMed

Domingo-Claros, Alicia; Larriba, Itziar; Rozman, Maruja; Irriguible, Dolors; Vallespí, Teresa; Aventin, Anna; Ayats, Ramon; Millá, Fuensanta; Solé, Francesc; Florensa, Lourdes; Gallart, Miquel; Tuset, Esperanza; Lopez, Carmen; Woessner, Soledad

2002-02-01

The terms acute erythroleukemia and AML-M6 are defined in the FAB classification as proliferations of dysplastic erythroid elements mixed with blasts of myeloid origin, but pure erythroid leukemias are not included. The recent WHO classification has a category of acute myeloid leukemia not otherwise categorized, which includes acute erythroid leukemia (M6) of two subtypes: M6a-erythroleukemia (erythroid/myeloid) and M6b-pure erythroid leukemia. The aims of this co-operative study were to discover the incidences of these different subtypes, and pay special attention to the morphology of these entities. We reviewed a series of 62 patients with erythroid neoplastic proliferations. Previous medical history, age, sex, peripheral blood and bone marrow cell counts, cytochemical stains, immunophenotype, and cytogenetics were evaluated at presentation. We analyzed the incidence of erythrocyte, leukocyte and platelet abnormalities in the peripheral blood. In bone marrow we analyzed dysplastic features of erythroblasts, granulocytic elements and the megakaryocytic lineage. Fifty-three patients met the criteria of M6a subtype of the WHO classification, and 2 were classified as having pure erythremia (M6b); 7 cases could not be classified according to the WHO criteria. Fifty-five patients presented with de novo acute leukemia, and seven patients had secondary acute leukemia. The most frequent dysplastic features in blood smears were: schistocytes, tear-drop and pincered cells in erythrocytes; hypogranulation and hyposegmentation in leukocytes; gigantism and hypogranulation in platelets. In bone marrow, megaloblastic changes, multinuclearity, karyorrhexis and basophilic stippling in erythroblasts; hypogranulation and gigantism in granulocytic series, and micromegakaryocytes and unconnected nuclei in megakarocytes were the most dysplastic features. A positive PAS reaction and increase of bone marrow iron with ring sideroblasts were common features. Trilineage dysplasia was present in 54% of cases. Dysplastic features in granulocytic elements were absent in 26% of patients and minimal erythroblastic dysplasia was observed in seven patients. A complex karyotype was seen in 27% of patients; chromosomes 5 and 7 were the most frequently involved. De novo acute erythroid leukemia was more frequent than secondary cases in our series. The most frequent type of acute erythroid proliferation was the WHO M6a subtype and the least the pure erythroid leukemia. We found a group of seven patients (11%) who could not be classified according to the WHO criteria. Morphologic findings of erythrocytes in peripheral blood, such as schistocytes, tear-drop and pincered cells, were outstanding features. Morphologic aspects remain one of the most important tools for diagnosing these entities.

Long-term clinical outcome and carrier phenotype in autosomal recessive hypophosphatemia caused by a novel DMP1 mutation.

PubMed

Mäkitie, Outi; Pereira, Renata C; Kaitila, Ilkka; Turan, Serap; Bastepe, Murat; Laine, Tero; Kröger, Heikki; Cole, William G; Jüppner, Harald

2010-10-01

Homozygous inactivating mutations in DMP1 (dentin matrix protein 1), the gene encoding a noncollagenous bone matrix protein expressed in osteoblasts and osteocytes, cause autosomal recessive hypophosphatemia (ARHP). Herein we describe a family with ARHP owing to a novel homozygous DMP1 mutation and provide a detailed description of the associated skeletal dysplasia and carrier phenotype. The two adult patients with ARHP, a 78-year-old man and his 66-year-old sister, have suffered from bone pain and lower extremity varus deformities since early childhood. With increasing age, both patients developed severe joint pain, contractures, and complete immobilization of the spine. Radiographs showed short and deformed long bones, significant cranial hyperostosis, enthesopathies, and calcifications of the paraspinal ligaments. Biochemistries were consistent with hypophosphatemia owing to renal phosphate wasting; markers of bone turnover and serum fibroblast growth factor 23 (FGF-23) levels were increased significantly. Nucleotide sequence analysis of DMP1 revealed a novel homozygous mutation at the splice acceptor junction of exon 6 (IVS5-1G > A). Two heterozygous carriers of the mutation also showed mild hypophosphatemia, and bone biopsy in one of these individuals showed focal areas of osteomalacia. In bone, DMP1 expression was absent in the homozygote but normal in the heterozygote, whereas FGF-23 expression was increased in both subjects but higher in the ARHP patient. The clinical and laboratory observations in this family confirm that DMP1 has an important role in normal skeletal development and mineral homeostasis. The skeletal phenotype in ARHP may be significantly more severe than in other forms of hypophosphatemic rickets.

Dental Abnormalities Caused by Novel Compound Heterozygous CTSK Mutations.

PubMed

Xue, Y; Wang, L; Xia, D; Li, Q; Gao, S; Dong, M; Cai, T; Shi, S; He, L; Hu, K; Mao, T; Duan, X

2015-05-01

Cathepsin K (CTSK) is an important protease responsible for degrading type I collagen, osteopontin, and other bone matrix proteins. The mutations in the CTSK gene can cause pycnodysostosis (OMIM 265800), a rare autosomal recessive bone dysplasia. Patients with pycnodysostosis have been reported to present specific dental abnormalities; however, whether these dental abnormalities are related to dysfunctional CTSK has never been reported. Here we investigated the histologic changes of cementum and alveolar bone in a pycnodysostosis patient, caused by novel compound heterozygous mutations in the CTSK gene (c.87 G>A p.W29X and c.848 A>G p.Y283C). The most impressive manifestations in tooth were extensive periradicular high-density clumps with unclear periodontal space by orthopantomography examination and micro-computed tomography scanning analysis. Hematoxylin/eosin and toluidine blue staining and atomic force microscopy analysis showed that the cementum became significantly thickened, softened, and full of cementocytes. The disorganized bone structure was the main character of alveolar bone. The p.W29X mutation may represent the loss-of-function allele with an earlier termination codon in the precursor CTSK polypeptide. Residue Y283 is highly conserved among papain-like cysteine proteases. Three-dimensional structure modeling analysis found that the loss of the hydroxybenzene residue in the Y283C mutation would interrupt the hydrogen network and possibly affect the self-cleavage of the CTSK enzyme. Furthermore, p.Y283C mutation did not affect the mRNA and protein levels of overexpressed CTSK in COS-7 system but did reduce CTSK enzyme activity. In conclusion, the histologic and ultrastructural changes of cementum and alveolar bone might be affected by CTSK mutation via reduction of its enzyme activity (clinical trial registration: ChiCTR-TNC-10000876). © International & American Associations for Dental Research 2015.

Obif, a Transmembrane Protein, Is Required for Bone Mineralization and Spermatogenesis in Mice

PubMed Central

Mizuhashi, Koji; Chaya, Taro; Kanamoto, Takashi; Omori, Yoshihiro; Furukawa, Takahisa

2015-01-01

Background Various kinds of transmembrane and secreted proteins play pivotal roles in development through cell-cell communication. We previously reported that Obif (Osteoblast induction factor, Tmem119), encoding a single transmembrane protein, is expressed in differentiating osteoblasts, and that Obif−/− mice exhibit significantly reduced bone volume in the femur. In the current study, we characterized the Obif protein and further investigated the biological phenotypes of a variety of tissues in Obif−/− mice. Results First, we found that O-glycosylation of the Obif protein occurs at serine residue 36 in the Obif extracellular domain. Next, we observed that Obif−/− mice exhibit bone dysplasia in association with significantly increased osteoid volume per osteoid surface (OV/OS) and osteoid maturation time (Omt), and significantly decreased mineral apposition rate (MAR) and bone formation rate per bone surface (BFR/BS). In addition, we observed that Obif−/− mice show a significant decrease in testis weight as well as in sperm number. By histological analysis, we found that Obif is expressed in spermatocytes and spermatids in the developing testis and that spermatogenesis is halted at the round spermatid stage in the Obif−/− testis that lacks sperm. However, the number of litters fathered by male mice was slightly reduced in Obif−/− mice compared with wild-type mice, although this was not statistically significant. Conclusions Our results, taken together with previous observations, indicate that Obif is a type Ia transmembrane protein whose N-terminal region is O-glycosylated. In addition, we found that Obif is required for normal bone mineralization and late testicular differentiation in vivo. These findings suggest that Obif plays essential roles in the development of multiple tissues. PMID:26207632

Obif, a Transmembrane Protein, Is Required for Bone Mineralization and Spermatogenesis in Mice.

PubMed

Mizuhashi, Koji; Chaya, Taro; Kanamoto, Takashi; Omori, Yoshihiro; Furukawa, Takahisa

2015-01-01

Various kinds of transmembrane and secreted proteins play pivotal roles in development through cell-cell communication. We previously reported that Obif (Osteoblast induction factor, Tmem119), encoding a single transmembrane protein, is expressed in differentiating osteoblasts, and that Obif-/- mice exhibit significantly reduced bone volume in the femur. In the current study, we characterized the Obif protein and further investigated the biological phenotypes of a variety of tissues in Obif-/- mice. First, we found that O-glycosylation of the Obif protein occurs at serine residue 36 in the Obif extracellular domain. Next, we observed that Obif-/- mice exhibit bone dysplasia in association with significantly increased osteoid volume per osteoid surface (OV/OS) and osteoid maturation time (Omt), and significantly decreased mineral apposition rate (MAR) and bone formation rate per bone surface (BFR/BS). In addition, we observed that Obif-/- mice show a significant decrease in testis weight as well as in sperm number. By histological analysis, we found that Obif is expressed in spermatocytes and spermatids in the developing testis and that spermatogenesis is halted at the round spermatid stage in the Obif-/- testis that lacks sperm. However, the number of litters fathered by male mice was slightly reduced in Obif-/- mice compared with wild-type mice, although this was not statistically significant. Our results, taken together with previous observations, indicate that Obif is a type Ia transmembrane protein whose N-terminal region is O-glycosylated. In addition, we found that Obif is required for normal bone mineralization and late testicular differentiation in vivo. These findings suggest that Obif plays essential roles in the development of multiple tissues.

Schimke immuno-osseous dysplasia: case report and review of 25 patients

PubMed Central

Saraiva, J.; Dinis, A.; Resende, C.; Faria, E.; Gomes, C.; Correia, A; Gil, J.; da Fonseca, N.

1999-01-01

Immuno-osseous dysplasia is characterised by spondyloepiphyseal dysplasia, lymphopenia with defective cellular immunity, and progressive renal disease. We describe a patient with a severe form of the disease, review the features of another 24 patients, and discuss the previous classification. The differences between the two groups are not striking, and although similarities are greater between affected sibs, the same diagnosis of Schimke immuno-osseous dysplasia should apply to them all. The aetiology and physiopathology of this rare osteochondrodysplasia of presumed autosomal recessive inheritance remain unknown.


Keywords: osteochondrodysplasia; immuno-osseous dysplasia; spondyloepiphyseal dysplasia; defective cellular immunity PMID:10528861

[CLINICAL CHARACTERISTICS OF CONGENITAL HEART DISEASES ASSOCIATED WITH CONNECTIVE TISSUE DISPLASIA AT CHILDREN LIVING IN EAST REGION OF KAZAKHSTAN].

PubMed

Madiyeva, M; Rymbayeva, T

2017-11-01

The frequency of the combination of congenital heart defects (CHD) and connective tissue dysplasia remains poorly understood. And connective tissue dysplasia enhance severity the clinical of CHD. The aim of the study was to conduct a clinical and laboratory analysis of combinations of congenital heart defects and connective tissue dysplasia in children of Semey and to determine the risk for the development of these pathologies. The object of the study is the children of Semey (East Kazakhstan) aged 1-14 with congenital heart defects (CHD), with connective tissue dysplasia, healthy children and their mothers. Definition complex clinical and laboratory studies in children with CHD and connective tissue dysplasia, and their mothers. In children with CHD, the frequency of external and visceral signs of dysplasia was high. In 88.1% of cases in children with CHD was diagnosed 2-3 degrees of dysplasia. Was found difference in the microelement composition of blood serum and of hemostasis in children with CHD were expressed by hypofibrinogenemia, hypocalcemia, hypomagnesemia. Excess of the frequency of signs of dysplasia in mothers over the control group to consider dysplasia as a factor that influences the clinical of CHD.

Runx2 is required for early stages of endochondral bone formation but delays final stages of bone repair in Axin2-deficient mice

PubMed Central

McGee-Lawrence, Meghan E.; Carpio, Lomeli R.; Bradley, Elizabeth W.; Dudakovic, Amel; Lian, Jane B.; van Wijnen, Andre J.; Kakar, Sanjeev; Hsu, Wei; Westendorf, Jennifer J.

2014-01-01

Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/− mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/− mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2−/−:Runx2+/− mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/− mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2−/−:Runx2+/− calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/− and double mutant Axin2−/−:Runx2+/− mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/− mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2−/− mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation. PMID:24973690

The association between cervical dysplasia, a short cervix, and preterm birth.

PubMed

Miller, Emily S; Sakowicz, Allie; Grobman, William A

2015-10-01

We sought to determine whether cervical dysplasia in the absence of an excisional procedure is associated with an increased risk of preterm birth (PTB) and whether that risk is independent of the presence of a short cervix. This is a cohort study including women with a singleton pregnancy who underwent routine cervical length assessment between 18-23 6/7 weeks of gestation, stratified by cervical dysplasia (ie, no prior dysplasia, prior dysplasia but no excisional procedure, or prior excisional procedure). The frequency of a short cervix (≤2.5 cm) and PTB were compared between groups and multivariable analyses were performed to identify whether: (1) dysplasia alone or a prior excisional procedure was associated with PTB; and (2) whether these factors remained independently associated with PTB after adjusting for the presence of a short cervix. Of the 18,528 women who met inclusion criteria, 3023 (16.3%) had prior dysplasia alone and 1356 (7.3%) had a prior excisional procedure. The frequency of a short cervix for women without dysplasia, with prior dysplasia alone, or with a prior excisional procedure was 0.8%, 1.0%, and 2.2%, respectively (P < .001). The frequency of PTB, respectively, was 6.4%, 6.5%, and 8.4% (P < .001). After adjusting for potential confounding factors, prior excisional procedure but not prior dysplasia alone was associated with PTB. Having a prior cervical excisional procedure but not dysplasia alone is associated with an increased risk of PTB. This association is independent of the presence of a short cervix. Copyright © 2015 Elsevier Inc. All rights reserved.