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PloS One 2014Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their α2β1 integrin as well as via...
Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their α2β1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3-6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed some distinct differences, with increased deposition of cartilage intermediate layer protein 1 and fibronectin in the chondroadherin deficient mice, more pronounced in the female. Other proteins show decreased levels in the deficient mice, particularly pronounced for matrilin-1, thrombospondin-1 and notably the members of the α1-antitrypsin family of proteinase inhibitors as well as for a member of the bone morphogenetic protein growth factor family. Thus, cartilage homeostasis is distinctly altered. The bone phenotype was expressed in several ways. The number of bone sialoprotein mRNA expressing cells in the proximal tibial metaphysic was decreased and the osteoid surface was increased possibly indicating a change in mineral metabolism. Micro-CT revealed lower cortical thickness and increased structure model index, i.e. the amount of plates and rods composing the bone trabeculas. The structural changes were paralleled by loss of function, where the null mice showed lower femoral neck failure load and tibial strength during mechanical testing at 4 months of age. The skeletal phenotype points at a role for chondroadherin in both bone and cartilage homeostasis, however, without leading to altered longitudinal growth.
Topics: Animals; Biomechanical Phenomena; Bone and Bones; Cartilage; Epiphyses; Extracellular Matrix Proteins; Femur; Gene Silencing; Growth Plate; Integrin-Binding Sialoprotein; Mice; Osteopontin; Phenotype; Proteome; RNA, Messenger; X-Ray Microtomography
PubMed: 23755099
DOI: 10.1371/journal.pone.0063080 -
Annali Di Stomatologia 2017Craniometaphyseal dysplasia is a rare hereditary bone disease presenting metaphyseal widening of the tubular bones, sclerosis of craniofacial bones and bony overgrowth...
INTRODUCTION
Craniometaphyseal dysplasia is a rare hereditary bone disease presenting metaphyseal widening of the tubular bones, sclerosis of craniofacial bones and bony overgrowth of the facial and skull bones. Craniometaphyseal dysplasia occurs in an autosomal dominant (AD) and an autosomal recessive (AR) form.
CASE REPORT
We present a 32-year-old patient arrived at our unit in May 2009. His main discomfort was a major limitation of the mouth opening, in the context of a craniofacial deformity. Relying on patient's medical history and the performed diagnostic tests, the diagnosis of craniometaphyseal dysplasia was made.
CONCLUSION
After careful evaluation of the clinical case, in accordance with the requirements of the patient, we opted for a surgical treatment aimed at correction of functional limitation of temporomandibular joint and aesthetic improvement of the facial bones. The stability of the clinical results led us to suggest and to undertake the surgical path, also due to the lack of safe and consolidated non-surgical treatments for the specific case.
PubMed: 29299192
DOI: 10.11138/ads/2017.8.2.045 -
Chang Gung Medical Journal 2011Reports of the efficacy of Salter's osteotomy have often been based on groups of patients with complex disease conditions and treatment. The purposes of this study were...
BACKGROUND
Reports of the efficacy of Salter's osteotomy have often been based on groups of patients with complex disease conditions and treatment. The purposes of this study were to document the results of patients with well-defined conditions, focusing on the onset and sequelae of osteonecrosis.
METHODS
The study participants consisted of 63 patients with unilateral hip dislocation who had undergone one-stage open reduction and Salter's innominate osteotomy between the ages of 1 and 3 years. The results were evaluated clinically by McKay's classification and radiologically by the modified Severin's classification. Early signs of osteonecrosis were identified by neck widening, epiphysis fragmentation, and presence of a metaphyseal growth disturbance line in the first year after the operation.
RESULTS
After a follow-up of 10 years on average, good clinical and radiographic results were noted in 89% and 92% of the patients, respectively. Osteonecrosis occurred in 30 hips, of which 14 subsequently developed femoral head deformity. Residual dysplasia was noted in 5 hips, mostly resulting from late-onset coxa valga. Eighty-five percent of the hips without osteonecrosis and 53% of the hips with osteonecrosis (p < 0.05) were classified as Severin class 1. No pre-operative factors were found to be associated with the occurrence of osteonecrosis.
CONCLUSION
One-stage open reduction and Salter's osteotomy was an effective treatment for developmental dysplasia of the hip after walking age. However, parents must be informed of the two major complications, osteonecrosis and residual dysplasia, that can lead to long-term morbidity.
Topics: Adolescent; Child; Child, Preschool; Female; Hip Dislocation, Congenital; Humans; Infant; Male; Osteonecrosis; Osteotomy
PubMed: 21392478
DOI: No ID Found -
Pediatric Radiology Nov 2000The aim of this study was to assess physeal fractures of the pediatric knee identified by MR imaging and to describe the MR findings of such fractures. The authors...
The aim of this study was to assess physeal fractures of the pediatric knee identified by MR imaging and to describe the MR findings of such fractures. The authors reviewed 315 consecutive pediatric knee MR examinations done to assess for traumatic injury. The MR images were reviewed for evidence of physeal fracture. Fractures were classified by the Salter-Harris system, and associated findings and injuries were noted. Plain radiographs and medical records were reviewed. Seven distal femoral physeal fractures (Salter II, n = 6; Salter III, n = 1) and two proximal tibia physeal fractures (Salter III, n = 1; complex Salter IV, n = 1) were identified. Magnetic resonance demonstrated widening of a portion of the physis with visualization of a metaphyseal/epiphyseal fracture line. Periosteal elevation was observed in six cases. Four patients had associated ligamentous or meniscal injuries. Plain radiographs were available for review in eight patients. Bone abnormalities suggesting fracture were evident in six of eight patients; however, the fracture was fully delineated in only one patient. The diagnosis or confirmation of fracture by MR changed clinical management in seven of eight patients in whom follow-up was available. Physeal fractures of the pediatric knee are occasionally diagnosed by MR. Magnetic resonance provides improved delineation of non-displaced physeal fractures of the knee, while simultaneously allowing for evaluation of soft tissue structures.
Topics: Adolescent; Child; Epiphyses; Female; Femoral Fractures; Humans; Knee Injuries; Magnetic Resonance Imaging; Male; Tibial Fractures
PubMed: 11100491
DOI: 10.1007/s002470000319 -
Child's Nervous System : ChNS :... Jul 2016Metaphyseal dysplasia (Pyle disease) is a rare autosomal recessive disease with impressive and characteristic radiological findings but relatively mild clinical...
INTRODUCTION
Metaphyseal dysplasia (Pyle disease) is a rare autosomal recessive disease with impressive and characteristic radiological findings but relatively mild clinical features. It is usually incidentally diagnosed, despite the impressive radiological findings of gross metaphyseal widening and thinning of cortical bone.
CASE REPORT
Herein, we report an exceptionally unusual case of metaphyseal dysplasia in association with chronic facial nerve palsy.
DISCUSSION
Chronic facial nerve palsy due to compression of the facial nerve in a patient with Pyle disease represents an unusual novelty. Furthermore, this case delineates the clinical spectrum and phenotype of such a rare clinical entity. To the best of our knowledge, this is the first time that such an association is being described.
Topics: Bone Diseases, Developmental; Child; Chronic Disease; Facial Nerve; Facial Paralysis; Female; Humans; Osteochondrodysplasias
PubMed: 26847543
DOI: 10.1007/s00381-016-3021-6 -
Annals of Pediatric Endocrinology &... Sep 2016Vitamin D hydroxylation-deficient rickets type 1A (VDDR1A) is an autosomal recessively-inherited disorder caused by mutations in encoding the 1α-hydroxylase enzyme. We...
Vitamin D hydroxylation-deficient rickets type 1A (VDDR1A) is an autosomal recessively-inherited disorder caused by mutations in encoding the 1α-hydroxylase enzyme. We report on a female patient with VDDR1A who presented with hypocalcemic seizure at the age of 13 months. The typical clinical and biochemical features of VDDR1A were found, such as hypocalcemia, increased alkaline phosphatase, secondary hyperparathyroidism and normal 25-hydroxyvitamin D3 (25(OH)D). Radiographic images of the wrist showed metaphyseal widening with cupping and fraying of the ulna and distal radius, suggesting rickets. A mutation analysis of the gene identified a homozygous mutation of c.589+1G>A in the splice donor site in intron 3, which was known to be pathogenic. Since that time, the patient has been under calcitriol and calcium treatment, with normal growth and development. During the follow-up period, she did not develop genu valgum, scoliosis, or nephrocalcinosis.
PubMed: 27777911
DOI: 10.6065/apem.2016.21.3.169 -
Ultrasound in Obstetrics & Gynecology :... Jul 2014It has recently been reported that fetuses with achondroplasia have a wider than expected femoral proximal diaphysis-metaphysis angle (femoral angle). The aim of this...
OBJECTIVES
It has recently been reported that fetuses with achondroplasia have a wider than expected femoral proximal diaphysis-metaphysis angle (femoral angle). The aim of this case-control study was to investigate this finding.
METHODS
Cases with confirmed achondroplasia (n = 6), small-for-gestational-age fetuses (n = 70) and a group of normal fetuses (n = 377) were included in this study. The ultrasound image of the femur was examined by two independent experienced observers blinded to the diagnosis, who measured the femoral angle. These values were converted into multiples of the expected median (MoM), after adjustment for gestational age and femur length. Prevalence of various prenatal ultrasound signs of achondroplasia was determined in affected fetuses. Intra- and interobserver agreement of measurement of femoral angle was assessed using 95% limits of agreement and kappa statistics.
RESULTS
The femoral angle can be measured accurately by ultrasound, and increases with both increasing gestational age and increasing femur length. The femoral angle-MoM was significantly higher in fetuses with achondroplasia than in the control group (1.36 vs 1.00 MoM, P < 0.001) and in the SGA group (1.36 vs 1.04 MoM, P < 0.001). It measured more than 130° in five of the six cases with achondroplasia (83.3%), which was the most consistent finding other than shortening of the long bones.
CONCLUSIONS
The femoral angle is wider in fetuses with achondroplasia. This new ultrasound sign appears promising as an additional discriminatory marker when clinicians are faced with a case of short long bones in the third trimester.
Topics: Achondroplasia; Adult; Case-Control Studies; Diaphyses; Female; Femur; Humans; Infant, Small for Gestational Age; Observer Variation; Pregnancy; Pregnancy Trimester, Third; ROC Curve; Regression Analysis; Single-Blind Method; Ultrasonography, Prenatal
PubMed: 24623391
DOI: 10.1002/uog.13339 -
American Journal of Medical Genetics.... Oct 2014Mutations in the type XI collagen alpha-1 chain gene (COL11A1) cause a change in protein structure that alters its interactions with collagens II and V, resulting in...
Mutations in the type XI collagen alpha-1 chain gene (COL11A1) cause a change in protein structure that alters its interactions with collagens II and V, resulting in abnormalities in cartilage and ocular vitreous. The most common type XI collagenopathies are dominantly inherited Stickler or Marshall syndromes, while severe recessive skeletal dysplasias, such as fibrochondrogenesis, occur less frequently. We describe a family with a severe skeletal dysplasia caused by a novel dominantly inherited COL11A1 mutation. The siblings each presented with severe myopia, hearing loss, micromelia, metaphyseal widening of the long bones, micrognathia, and airway compromise requiring tracheostomy. The first child lived for over 2 years, while the second succumbed at 5 months of age. Their mother has mild rhizomelic shortening of the limbs, brachydactyly, and severe myopia. Sequencing of COL11A1 revealed a novel deleterious heterozygous mutation in COL11A1 involving the triple helical domain in both siblings, and a mosaic mutation in their mother, indicating germline mosaicism with subsequent dominant inheritance. These are the first reported individuals with a dominantly inherited mutation in COL11A1 associated with a severe skeletal dysplasia. The skeletal involvement is similar to, yet milder than fibrochondrogenesis and allowed for survival beyond the perinatal period. These cases highlight both a novel dominant COL11A1 mutation causing a significant skeletal dysplasia and the phenotypic heterogeneity of collagenopathies.
Topics: Bone Diseases, Developmental; Collagen Type XI; Female; Hearing Loss; Humans; Musculoskeletal Abnormalities; Mutation; Myopia; Pedigree
PubMed: 25091507
DOI: 10.1002/ajmg.a.36688 -
Medicine Aug 2018X-linked dominant hypophosphatemia rickets (XLH, OMIM 307800) is the most common hereditary hypophosphatemic rickets and characterized by growth retardation, skeletal...
RATIONALE
X-linked dominant hypophosphatemia rickets (XLH, OMIM 307800) is the most common hereditary hypophosphatemic rickets and characterized by growth retardation, skeletal malformations, dental dysplasia, spontaneous fractures and osteomalacia. PHEX gene was identified for XLH and novel mutations were consistent with loss of function.
PATIENT CONCERNS
Case1: the proband 1 III3 in family 1 was a fourteen-year-old boy with bowing of bilateral legs, obviously enlarged joints, tooth absence and difficulty in walking; X-rays showed bilateral femoral multiple fractures with sclerosis at the fracture edge. Case 2: the proband 2 III2, a five-year-old boy in family 2, showed growth retardation, dental dysplasia, gingiva abscess and bilateral legs malformations; X-rays showed low bone density, delayed bone age, bowing of legs, frayed and widened metaphyses of the distal femurs and proximal tibias. Both of their mothers suffered from skeletal malformations, tooth absence and were performed with osteotomy due to fractures of lower limb. Their biochemical parameters showed hypophosphatemia, elevated alkaline phosphatase.
DIAGNOSES
X-linked dominant hypophosphatemia rickets (XLH).
INTERVENTIONS AND OUTCOMES
Treatment with high doses of phosphate and 1,25-dihydroxyvitamin D3, the height of proband 2 increased 10 cm and femoral Multiple fracture of proband1 almost healed after treatment for 6 months and the patients's PHEX gene was investigated.
LESSONS
Two novel pathogenic PHEX mutations were found: c.497delG in family 1 and c.388G> T in family 2, both of which caused early termination of translation and produced truncated protein. Serum FGF23 concentration in our XLH patients were obviously higher than the normal and may be related to age to some extent. Early initiation of treatment produces better effect.
Topics: Adolescent; Adult; Child, Preschool; Familial Hypophosphatemic Rickets; Female; Fibroblast Growth Factor-23; Humans; Male; Mutation; PHEX Phosphate Regulating Neutral Endopeptidase; Pedigree
PubMed: 30075510
DOI: 10.1097/MD.0000000000011453 -
Studies in History and Philosophy of... Dec 2010This article discusses the Tibetan notion of rlung, usually translated as: 'wind', but perhaps better understood as a close equivalent of pneuma in the Greek tradition,...
This article discusses the Tibetan notion of rlung, usually translated as: 'wind', but perhaps better understood as a close equivalent of pneuma in the Greek tradition, or qi in the Chinese tradition. The article focuses on the way rlung provides a useful prism through which concepts of health, illness and disease may be observed in a cross-cultural perspective. An analysis of syndromes linked with rlung in a Tibetan cultural context illuminates some of the ways in which culture determines particular syndromes. The article raises a number of questions which are relevant for a more general multicultural approach to concepts of health, illness and disease. The article argues that notions of rlung/pneuma/wind/ qi constitute a particularly interesting area for an exploration of culture-bound syndromes, as they reside in the meeting point between material and non-material, physical and mental, as well as the psychological, spiritual and religious. They are hence fundamental for a more cross-cultural approach to the mind-body problem. The article also deals with the significance of history of medicine, particularly histories of medicine, which attempt to widen the scope of the traditional Eurocentric narrative of the history of medicine, in dealing with questions such as concepts of health and illness. Allowing alternative narratives-whether narratives of patients, other cultures or historical ones-can enhance our understanding of what health, illness and disease are. Discussing perceptions of the body as culturally defined is not only important from a philosophical or historical point of view, but also has important practical ramifications, which are particularly crucial in our global age.
Topics: Cross-Cultural Comparison; Culture; Disease; History of Medicine; History, Ancient; Humans; Medicine, Traditional; Mind-Body Relations, Metaphysical; Qi; Syndrome; Tibet; Wind
PubMed: 21112005
DOI: 10.1016/j.shpsc.2010.10.005