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Clinica Chimica Acta; International... May 2016Craniometaphyseal dysplasia (CMD) is a rare genetic disorder that is characterized by progressive sclerosis of the craniofacial bones and metaphyseal widening of long...
BACKGROUND
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.
CASE REPORT
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.
CONCLUSIONS
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.
Topics: Alkaline Phosphatase; Bone Diseases, Developmental; Craniofacial Abnormalities; Exons; Female; Heterozygote; Humans; Hyperostosis; Hypertelorism; Hypocalcemia; Hypophosphatemia; Infant; Male; Mutation; Parathyroid Hormone; Pedigree; Phosphate Transport Proteins; Rickets
PubMed: 26820766
DOI: 10.1016/j.cca.2016.01.021 -
Radiographics : a Review Publication of... 2015A growing number of magnetic resonance (MR) imaging studies of the shoulder are being performed as a result of greater and earlier participation of children and...
A growing number of magnetic resonance (MR) imaging studies of the shoulder are being performed as a result of greater and earlier participation of children and adolescents in competitive sports such as softball and baseball. However, scant information is available regarding the MR imaging features of the normal sequential development of the shoulder. The authors discuss the radiographic and MR imaging appearances of the normal musculoskeletal maturation patterns of the shoulder, with emphasis on (a) development of secondary ossification centers of the glenoid (including the subcoracoid and peripheral glenoid ossification centers); (b) development of preossification and secondary ossification centers of the humeral head and the variable appearance and number of the secondary ossification centers of the distal acromion, with emphasis on the formation of the os acromiale; (c) development of the growth plates, glenoid bone plates, glenoid bare area, and proximal humeral metaphyseal stripe; and (d) marrow signal alterations in the distal humerus, acromion, and clavicle. In addition, the authors discuss various imaging interpretation pitfalls inherent to the normal skeletal maturation of the shoulder, examining clues that may help distinguish normal development from true disease (eg, osteochondral lesions, labral tears, abscesses, fractures, infection, tendon disease, acromioclavicular widening, and os acromiale). Familiarity with the timing, location, and appearance of maturation patterns in the pediatric shoulder is crucial for correct image interpretation.
Topics: Acromioclavicular Joint; Adolescent; Child; Child, Preschool; Diagnostic Errors; Female; Humans; Humerus; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Pediatrics; Reproducibility of Results; Scapula; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 26172355
DOI: 10.1148/rg.2015140254 -
Indian Journal of Orthopaedics 2015The anterior cruciate ligament (ACL) is one of the major stabilizing factor of the knee that resist anterior translation, valgus and varus forces. ACL is the most...
BACKGROUND
The anterior cruciate ligament (ACL) is one of the major stabilizing factor of the knee that resist anterior translation, valgus and varus forces. ACL is the most commonly ruptured ligament of the knee. The graft fixation to bone is considered to be the weakest link of the reconstruction. According to the parallel forces to the tibial drill hole and the quality of tibial metaphyseal bone is inferior to femoral bone stock, graft fixation to the tibia is more difficult to secure. AperFix system (Cayenne Medical, Inc., Scottsdale, Arizona, USA) which consists femoral and tibial component that includes bioinert polymer polyetheretherketone (PEEK) is one of the new choice for ACL reconstruction surgery. aim of this study was to assess the clinical outcomes and fixation durability of the AperFix (Cayenne Madical, Inc., Scottsdale, Arizona, USA) system and to determine the effect of patient's age in arthroscopic reconstruction of the anterior cruciate ligament.
MATERIALS AND METHODS
Patients with symptomatic anterior cruciate ligament rupture underwent arthroscopic reconstruction. Patients were evaluated in terms of range of motion (ROM) values; Lysholm, Cincinati and Tegner activity scales; laxity testing and complications. Femoral tunnel widening was assessed by computer tomography scans. Early postoperative and last followup radiographs were compared.
RESULTS
Fifty one patients were evaluated with mean followup of 29 months (range 25-34 months). Mean age at the surgery was 26.5 ± 7.2 years. Lysholm, Cincinati and Tegner activity scales were significantly higher from preoperative scores (Lysholm scores: Preoperative: 51.4 ± 17.2, postoperative: 88.6 ± 7.7 [P < 0.001]; Tegner activity scores: Preoperative 3.3 ± 1.38, postoperative: 5.3 ± 1.6 [P < 0.001]; Cincinati scores: Preoperative: 44.3 ± 17, postoperative: 81.3 ± 13.9 [P < 0.001]). The mean femoral tunnel diameter increased significantly from 9.94 ± 0.79 mm postoperatively to 10.79 ± 0.95 mm (P < 0.05). The mean ROM deficit (involved vs. contra knee) was -7.2 ± 16 (P < 0.001). There was no significant difference for knee score, ROM deficits (<30 years: -7.3 ± 15 and >30 years -7.06 ± 19) and femoral tunnel enlargement (<30 years: 0.83 ± 0.52 and >30 years 0.87 ± 0.43) of the patients with below and above 30 year. There was no significant difference for knee scores and femoral tunnel enlargement between patients with meniscal injuries and don't have meniscus lesions.
CONCLUSION
The AperFix system gives satisfactory clinical and radiological results with low complication rate. However, long term clinical and radiological results are needed to decide the ideal anterior cruciate ligament reconstruction method.
PubMed: 26015602
DOI: 10.4103/0019-5413.152436 -
Journal of Pediatric Hematology/oncology May 2015Ghosal hematodiaphyseal dysplasia (GHDD) is a recently recognized cause of steroid-responsive anemia. We would like to report 3 cases of GHDD who presented in early...
Ghosal hematodiaphyseal dysplasia (GHDD) is a recently recognized cause of steroid-responsive anemia. We would like to report 3 cases of GHDD who presented in early childhood with moderate to severe anemia, splenomegaly, and a hypocellular marrow with increased reticulin. They were easily diagnosed with long-bone x-rays showing diaphyseal and metaphyseal widening and loss of diaphyseal constriction. All cases dramatically responded to oral steroid and no longer needed blood transfusion. They required steroid at low doses for long term (up to 5 y). GHDD is easy to diagnose with long-bone radiography and consistently responds to steroid. It should therefore be considered as a differential diagnosis of unusual anemia in early childhood, especially in children from the Middle East or the Indian subcontinent.
Topics: Adrenal Cortex Hormones; Anemia; Anemia, Refractory; Child, Preschool; Diagnosis, Differential; Female; Humans; Male; Osteochondrodysplasias
PubMed: 25374284
DOI: 10.1097/MPH.0000000000000279 -
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 -
Social Science & Medicine (1982) Mar 2015'One World One Health' (OWOH), 'One Medicine' and 'One Health' are all injunctions to work across the domains of veterinary, human and environmental health. In large...
'One World One Health' (OWOH), 'One Medicine' and 'One Health' are all injunctions to work across the domains of veterinary, human and environmental health. In large part they are institutional responses to growing concerns regarding shared health risks at the human, animal and environmental interfaces. Although these efforts to work across disciplinary boundaries are welcome, there are also risks in seeking unity, not least the tendency of one health visions to reduce diversity and to under-value the local, contingent and practical engagements that make health possible. This paper uses insights from Geography and Science and Technology Studies along with multi-sited and multi-species qualitative fieldwork on animal livestock and zoonotic influenzas in the UK, to highlight the importance of those practical engagements. After an introduction to one health, I argue that there is a tendency in OWOH visions to focus on contamination and transmission of pathogens rather than the socio-economic configuration of disease and health, and this tendency conforms to or performs what sociologist John Law calls a one world metaphysics. Following this, three related field cases are used to demonstrate that health is dependent upon a patchwork of practices, and is configured in practice by skilled people, animals, micro-organisms and their social relations. From surveillance for influenza viruses to tending animals, good health it turns out is dependent on an ability to construct common sense from a complex of signs, responses and actions. It takes, in other words, more than one world to make healthy outcomes. In light of this, the paper aims to, first, loosen any association between OWOH and a one world-ist metaphysics, and, second, to radicalize the inter-disciplinary foundations of OWOH by both widening the scope of disciplinarity as well as attending to how different knowledges are brought together.
Topics: Animals; Birds; Environmental Health; Global Health; Health Policy; Humans; Influenza in Birds; Risk Factors; Social Conditions; Socioeconomic Factors; Zoonoses
PubMed: 25022470
DOI: 10.1016/j.socscimed.2014.07.007 -
Bone Jul 2014RANKL is a key regulator of bone resorption and osteoclastogenesis. Denosumab is a fully human IgG2 monoclonal antibody that inhibits bone resorption by binding and...
RANKL is a key regulator of bone resorption and osteoclastogenesis. Denosumab is a fully human IgG2 monoclonal antibody that inhibits bone resorption by binding and inhibiting the activity of RANKL. To determine the effects of denosumab on pre- and postnatal skeletal growth and development, subcutaneous injections of 0 (control) or 50 mg/kg/month denosumab were given to pregnant cynomolgus monkeys from approximately gestation day (GD) 20 until parturition (up to 6 doses). For up to 6 months postpartum (birth day [BD] 180/181), evaluation of the infants included skeletal radiographs, bone biomarkers, and oral examinations for assessment of tooth eruption. Infant bones were collected at necropsy for densitometry, biomechanical testing, and histopathologic evaluation from control and denosumab-exposed infants on BD1 (or within 2 weeks of birth) and BD181, and from infants that died or were euthanized moribund from BD5 to BD69. In all denosumab-exposed infants, biomarkers of bone resorption and formation were markedly decreased at BD1 and BD14 and slightly greater at BD91 vs. control, then similar to control values by BD181. Spontaneous long bone fractures were detected clinically or radiographically in 4 denosumab-exposed infants at BD28 and BD60, with evidence of radiographic healing at ≥BD60. In BD1 infants exposed to denosumab in utero, radiographic evaluations of the skeleton revealed decreased long bone length; a generalized increased radio-opacity of the axial and appendicular skeleton and bones at the base of the skull with decreased or absent marrow cavities, widened growth plates, flared/club-shaped metaphysis, altered jaw/skull shape, and reduced jaw length; and delayed development of secondary ossification centers. Densitometric evaluations in these infants demonstrated a marked increase in bone mineral density at trabecular sites, but cortical bone mineral density was decreased. Histologically, long bone cortices were attenuated and there was an absence of osteoclasts. Bones with active endochondral ossification consisted largely of a dense network of retained primary spongiosa with reduced marrow space consistent with an osteopetrotic phenotype. A minimal increase in growth plate thickness largely due to the expansion of the hypertrophic zone was present. Retained woven bone was observed in bones formed by intramembranous ossification, consistent with absence of bone remodeling. These changes in bone tissue composition and geometry were reflected in reduced biomechanical strength and material properties of bones from denosumab-exposed infants. Material property changes were characterized by increased tissue brittleness reflected in reductions in calculated material toughness at the femur diaphysis and lack of correlation between energy and bone mass at the vertebra; these changes were likely the basis for the increased skeletal fragility (fractures). Although tooth eruption was not impaired in denosumab-exposed infants, the reduced growth and increased bone density of the mandible resulted in dental abnormalities consisting of tooth malalignment and dental dysplasia. Radiographic changes at BD1 persisted at BD28, with evidence of resumption of bone resorption and remodeling observed in most infants at BD60 and/or BD90. In 2 infants euthanized on BD60 and BD69, there was histologic and radiographic evidence of subphyseal/metaphyseal bone resorption accompanied by multiple foci of ossification in growth plates that were markedly increased in thickness. In infants necropsied at BD181, where systemic exposure to denosumab had been below limits of quantitation for approximately 3months, there was largely full recovery from all bone-related changes observed earlier postpartum, including tissue brittleness. Persistent changes included dental dysplasia, decreased bone length, reduced cortical thickness, and decreased peak load and ultimate strength at the femur diaphysis. In conclusion, the skeletal and secondary dental effects observed in infant monkeys exposed in utero to denosumab are consistent with the anticipated pharmacological activity of denosumab as a monoclonal antibody against RANKL and inhibitor of osteoclastogenesis. The resulting inhibition of resorption impaired both bone modeling and remodeling during skeletal development and growth. The skeletal phenotype of these infant monkeys resembles human infants with osteoclast-poor osteopetrosis due to inactivating mutations of RANK or RANKL.
Topics: Animals; Antibodies, Monoclonal, Humanized; Bone Remodeling; Denosumab; Female; Macaca fascicularis; Osteoclasts; Osteopetrosis; Phenotype; Pregnancy; Prenatal Exposure Delayed Effects; Tomography, X-Ray Computed; Tooth Eruption
PubMed: 24727159
DOI: 10.1016/j.bone.2014.04.002 -
Journal of Dental Research Jun 2014Craniometaphyseal dysplasia (CMD) is a rare genetic disorder encompassing hyperostosis of craniofacial bones and metaphyseal widening of tubular bones. Dental...
Craniometaphyseal dysplasia (CMD) is a rare genetic disorder encompassing hyperostosis of craniofacial bones and metaphyseal widening of tubular bones. Dental abnormalities are features of CMD that have been little discussed in the literature. We performed dentofacial examination of patients with CMD and evaluated consequences of orthodontic movement in a mouse model carrying a CMD knock-in (KI) mutation (Phe377del) in the Ank gene. All patients have a history of delayed eruption of permanent teeth. Analysis of data obtained by cone-beam computed tomography showed significant bucco-lingual expansion of jawbones, more pronounced in mandibles than in maxillae. There was no measurable increase in bone density compared with that in unaffected individuals. Orthodontic cephalometric analysis showed that patients with CMD tend to have a short anterior cranial base, short upper facial height, and short maxillary length. Microcomputed tomography (micro-CT) analysis in homozygous Ank (KI/KI) mice, a model for CMD, showed that molars can be moved by orthodontic force without ankylosis, however, at a slower rate compared with those in wild-type Ank (+/+) mice (p < .05). Histological analysis of molars in Ank (KI/KI) mice revealed decreased numbers of TRAP(+) osteoclasts on the bone surface of pressure sides. Based on these findings, recommendations for the dental treatment of patients with CMD are provided.
Topics: Acid Phosphatase; Animals; Bone Density; Bone Diseases, Developmental; Cephalometry; Cone-Beam Computed Tomography; Craniofacial Abnormalities; Disease Models, Animal; Gene Knock-In Techniques; Humans; Hyperostosis; Hypertelorism; Isoenzymes; Mandible; Maxilla; Mice; Mutation; Osteoclasts; Phenylalanine; Phosphate Transport Proteins; Sequence Deletion; Skull Base; Tartrate-Resistant Acid Phosphatase; Tooth Abnormalities; Tooth Movement Techniques; Vertical Dimension; X-Ray Microtomography
PubMed: 24663682
DOI: 10.1177/0022034514529304 -
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.... Apr 2014We report on a consanguineous Lebanese family in which two sibs had pre- and post-natal growth retardation, developmental delay, large anterior fontanel, prominent...
We report on a consanguineous Lebanese family in which two sibs had pre- and post-natal growth retardation, developmental delay, large anterior fontanel, prominent forehead, low-set ears, depressed nasal bridge, short nose, anteverted nares, increased nasal width, prominent abdomen, and short limbs. Radiographs disclosed the presence of wormian bones, platyspondyly, decreased interpedicular distance at the lumbar vertebrae, square iliac bones, horizontal acetabula, trident acetabula, hypoplastic ischia, partial agenesis of the sacrum, ribs with cupped ends, short long bones with abnormal modeling, slight widening of the distal femoral metaphyses, and delayed epiphyseal ossification. Both sibs had a severe cardiomegaly and died at around 24 months from a heart failure. Differential diagnosis suggests that this is a second family presenting a newly described early lethal chondrodysplasia first reported by [Mégarbané et al. (2008); Am J Med Genet Part A 146A:2916-2919].
Topics: Bone Diseases, Developmental; Child, Preschool; Developmental Disabilities; Genes, Recessive; Humans; Male; Osteochondrodysplasias; Siblings
PubMed: 24458487
DOI: 10.1002/ajmg.a.36372