DOCSLIB.ORG

Blueprint Genetics Osteopetrosis and Dense Bone Dysplasia Panel

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Osteopetrosis and Dense Bone Dysplasia Panel Test code: MA2001 Is a 25 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of osteopetrosis. The genes on this panel are included in the Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders Panel. About Osteopetrosis and Dense Bone Dysplasia Autosomal dominant osteopetrosis (ADO, also known as Albers-Schönberg disease) is typically an adult-onset, more benign form whereas autosomal recessive osteopetrosis (ARO), also termed malignant infantile osteopetrosis, presents soon after birth, is often severe and leads to death if left untreated. Autosomal recessive osteopetrosis (ARO) is a genetically and phenotypically heterogeneous disease; most forms result from late endosomal trafficking defects that prevent osteoclast ruffled‐border formation. Hematopoietic stem cell transplantation (HSCT) can cure ARO if given in early life to patients with osteoclast‐intrinsic disease without neurodegenerative complications. New treatments that target RANKL/RANK signaling offer promise in ARO subtypes that currently cannot be cured by HSCT and to prevent hypercalcemia after HSCT. Paget’s disease is a common metabolic bone disease characterized by focal abnormalities of increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Bone lesions in this disorder show evidence of increased osteoclastic bone resorption and disorganized bone structure. Genetic factors play an important role in the disease. In some cases, Paget’s disease is inherited in an autosomal dominant manner and the most common cause for this is a mutation in the SQSTM1 gene. Mutations in TNFRSF11A, TNFRSF11B and VCP have been identified in rare syndromes with Paget’s disease- like features. Availability 4 weeks Gene Set Description Genes in the Osteopetrosis and Dense Bone Dysplasia Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD AMER1 Osteopathia striata with cranial sclerosis XL 14 40 ANKH Calcium pyrophosphate deposition disease (familial chondrocalcinosis AD 13 20 type 2), Craniometaphyseal dysplasia autosomal dominant type CA2 Osteopetrosis, with renal tubular acidosis AR 9 31 CLCN7 Osteopetrosis AD/AR 15 98 COL1A1 Ehlers-Danlos syndrome, Caffey disease, Osteogenesis imperfecta AD 352 962 type 1, Osteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4 CTSK Pycnodysostosis AR 35 58 DLX3 Amelogenesis imperfecta, Trichodontoosseous syndrome AD 5 11 FAM20C Hypophosphatemia, hyperphosphaturia, dental anomalies, AR 13 25 intracerebral calcifications and osteosclerosis (Raine syndrome) https://blueprintgenetics.com/ GJA1* Oculodentodigital dysplasia mild type, Oculodentodigital dysplasia AD/AR 31 107 severe type, Syndactyly type 3 LEMD3 Buschke-Ollendorff syndrome, Osteopoikilosis AD 13 32 LRP4 Cenani-Lenz syndactyly syndrome, Sclerosteosis, Myasthenic AD/AR 14 28 syndrome, congenital LRP5* Van Buchem disease, Osteoporosis-pseudoglioma syndrome, AD/AR/Digenic 57 196 Hyperostosis, endosteal, Osteosclerosis, Exudative vitreoretinopathy, Osteopetrosis late-onset form type 1, LRP5 primary osteoporosis OSTM1 Osteopetrosis, autosomal recessive 5 AR 5 9 PTDSS1 Lenz-Majewski hyperostotic dwarfism AD 5 7 PTH1R Metaphyseal chondrodysplasia Jansen type, Failure of tooth eruption, AD/AR 13 43 Eiken dysplasia, Blomstrand dysplasia SLC29A3 Histiocytosis-lymphadenopathy plus syndrome, Dysosteosclerosis AR 17 25 SLCO2A1 Hypertrophic osteoarthropathy AD/AR 13 72 SNX10 Osteopetrosis, autosomal recessive 8 AR 3 13 SOST Craniodiaphyseal dysplasia, autosomal dominant, Sclerosteosis 1, van AD/AR 6 14 Buchem disease TCIRG1 Osteopetrosis, severe neonatal or infantile forms (OPTB1) AD/AR 48 130 TGFB1 Diaphyseal dysplasia Camurati-Engelmann AD 15 23 TNFRSF11A Familial expansile osteolysis, Paget disease of bone, Osteopetrosis, AD/AR 8 24 severe neonatal or infantile forms (OPTB1) TNFRSF11B Paget disease of bone, juvenile AR 8 18 TNFSF11 Osteopetrosis, autosomal recessive 2 AR 3 5 TYROBP Nasu-Hakola disease, Polycystic lipomembranous osteodysplasia with AR 8 14 sclerosing leukoencephalopathy *Some regions of the gene are duplicated in the genome. Read more. # The gene has suboptimal coverage (means <90% of the gene’s target nucleotides are covered at >20x with mapping quality score (MQ>20) reads), and/or the gene has exons listed under Test limitations section that are not included in the panel as they are not sufficiently covered with high quality sequence reads. The sensitivity to detect variants may be limited in genes marked with an asterisk (*) or number sign (#). Due to possible limitations these genes may not be available as single gene tests. Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR), mitochondrial (mi), X-linked (XL), X-linked dominant (XLD) and X-linked recessive (XLR); ClinVar refers to the number of variants in the gene classified as pathogenic or likely pathogenic in this database (ClinVar); HGMD refers to the number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD). The list of associated, gene specific phenotypes are generated from CGD or Mitomap databases. https://blueprintgenetics.com/ Non-coding disease causing variants covered by the panel Gene Genomic location HG19 HGVS RefSeq RS-number ANKH Chr5:14871567 c.-11C>T NM_054027.4 CLCN7 Chr16:1506057 c.916+57A>T NM_001287.5 CLCN7 Chr16:1507356 c.739-18G>A NM_001287.5 rs371893553 COL1A1 Chr17:48266910 c.2668-11T>G NM_000088.3 rs786205505 COL1A1 Chr17:48267594 c.2451+94G>T NM_000088.3 COL1A1 Chr17:48267611 c.2451+77C>T NM_000088.3 rs72651665 COL1A1 Chr17:48268147 c.2343+31T>A NM_000088.3 COL1A1 Chr17:48272201 c.1354-12G>A NM_000088.3 rs72648337 COL1A1 Chr17:48273368 c.1003-43_1003-32delTGCCATCTCTTC NM_000088.3 rs72645359 COL1A1 Chr17:48273574 c.958-18_958-15delTTCC NM_000088.3 rs72645351 COL1A1 Chr17:48273742 c.904-14G>A NM_000088.3 COL1A1 Chr17:48273743 c.904-15T>A NM_000088.3 CTSK Chr1:150778521 c.244-29A>G NM_000396.3 PTH1R Chr3:46939842 c.544-25_544-23delCTG NM_000316.2 PTH1R Chr3:46942604 c.1049+29C>T NM_000316.2 SLC29A3 Chr10:73122778 c.*413G>A NM_018344.5 TCIRG1 Chr11:67806587 c.-5+1G>C/T NM_006019.3 TCIRG1 Chr11:67806587 c.-5+1G>C NM_006019.3 TCIRG1 Chr11:67806587 c.-5+1G>T NM_006019.3 TCIRG1 Chr11:67816893 c.1887+132T>C NM_006019.3 TCIRG1 Chr11:67816903 c.1887+142T>A NM_006019.3 TCIRG1 Chr11:67816907 c.1887+146G>A NM_006019.3 TCIRG1 Chr11:67816910 c.1887+149C>T NM_006019.3 Test Strengths The strengths of this test include: CAP accredited laboratory CLIA-certified personnel performing clinical testing in a CLIA-certified laboratory Powerful sequencing technologies, advanced target enrichment methods and precision bioinformatics pipelines ensure superior analytical performance Careful construction of clinically effective and scientifically justified gene panels https://blueprintgenetics.com/ Some of the panels include the whole mitochondrial genome (please see the Panel Content section) Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level Our publicly available analytic validation demonstrating complete details of test performance ~2,000 non-coding disease causing variants in our clinical grade NGS assay for panels (please see ‘Non-coding disease causing variants covered by this panel’ in the Panel Content section) Our rigorous variant classification scheme Our systematic clinical interpretation workflow using proprietary software enabling accurate and traceable processing of NGS data Our comprehensive clinical statements Test Limitations Genes with partial, or whole gene, segmental duplications in the human genome are marked with an asterisk (*) if they overlap with the UCSC pseudogene regions. The technology may have limited sensitivity to detect variants in genes marked with these symbols (please see the Panel content table above). This test does not d etect the following: Complex inversions Gene conversions Balanced translocations Some of the panels include the whole mitochondrial genome (please see the Panel Content section) Repeat expansion disorders unless specifically mentioned Non-coding variants deeper than ±20 base pairs from exon-intron boundary unless otherwise indicated (please see above Panel Content / non-coding variants covered by the panel). This test may not reliably detect the following: Low level mosaicism in nuclear genes (variant with a minor allele fraction of 14.6% is detected with 90% probability) Stretches of mononucleotide repeats Low level heteroplasmy in mtDNA (>90% are detected at 5% level) Indels larger than 50bp Single exon deletions or duplications Variants within pseudogene regions/duplicated segments Some disease causing variants present in mtDNA are not detectable from blood, thus post-mitotic tissue such as skeletal muscle may be required for establishing molecular diagnosis. The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics. For additional information, please refer to the Test performance section and see our Analytic Validation. Test Performance The genes on the panel have been carefully selected based on scientific literature, mutation databases and our experience. Our panels are sectioned from our high-quality, clinical grade NGS assay. Please see our sequencing and detection
Recommended publications
  • Differential Diagnosis: Brittle Bone Conditions Other Than OI

    Differential Diagnosis: Brittle Bone Conditions Other Than OI

    Facts about Osteogenesis Imperfecta Differential Diagnosis: Brittle Bone Conditions Other than OI Fragile bones are the hallmark feature of osteogenesis imperfecta (OI). The mutations that cause OI lead to abnormalities within bone that result in increased bone turnover; reduced bone mineral content and decreased bone mineral density. The consequence of these changes is brittle bones that fracture easily. But not all cases of brittle bones are OI. Other causes of brittle bones include osteomalacia, disuse osteoporosis, disorders of increased bone density, defects of bone, and tumors. The following is a list of conditions that share fragile or brittle bones as a distinguishing feature. Brief descriptions and sources for further information are included. Bruck Syndrome This autosomal recessive disorder is also referred to as OI with contractures. Some people now consider this to be a type of OI. National Library of Medicine Genetics Home Reference: http://ghr.nlm.nih.gov Ehlers-Danlos Syndrome (EDS) Joint hyperextensibility with fractures; this is a variable disorder caused by several gene mutations. Ehlers-Danlos National Foundation http://www.ednf.org Fibrous Dysplasia Fibrous tissue develops in place of normal bone. This weakens the affected bone and causes it to deform or fracture. Fibrous Dysplasia Foundation: https://www.fibrousdysplasia.org ‎ Hypophosphatasia This autosomal recessive disorder affects the development of bones and teeth through defects in skeletal mineralization. Soft Bones: www.softbones.org; National Library of Medicine Genetics Home Reference: http://ghr.nlm.nih.gov/condition Idiopathic Juvenile Osteoporosis A non-hereditary transient form of childhood osteoporosis that is similar to mild OI (Type I) National Osteoporosis Foundation: www.nof.org McCune-Albright Syndrome This disorder affects the bones, skin, and several hormone-producing tissues.
  • Marble Bone Disease: a Rare Bone Disorder

    Marble Bone Disease: a Rare Bone Disorder

    Open Access Case Report DOI: 10.7759/cureus.339 Marble Bone Disease: A Rare Bone Disorder Eswaran Arumugam 1 , Maheswari Harinathbabu 2 , Ranjani Thillaigovindan 1 , Geetha Prabhu 1 1. Prosthodontics, Thai Moogambigai Dental College and Hospital 2. Oral Medicine and Radiology, Siva Multi Speciality Dental Clinic Corresponding author: Eswaran Arumugam, [email protected] Abstract Osteopetrosis, or marble bone disease, is a rare skeletal disorder due to a defective function of the osteoclasts. This defect renders bones more susceptible to osteomyelitis due to decreased vascularity. This disorder is inherited as autosomal dominant and autosomal recessive. Healthcare professionals should urge these patients to maintain their oral health as well as general health, as this condition makes these patients more susceptible to frequent infections and fractures. This case report emphasizes the signs and symptoms of marble bone disease and presents clinical and radiographic findings. Categories: Physical Medicine & Rehabilitation, Miscellaneous Keywords: osteopetrosis, marble bone disease, autosomal recessive, dense sclerotic bone Introduction Osteopetrosis (literally "stone bone," also known as marble bone disease or Albers-Schonberg disease) is an extremely rare inherited disorder where the bones harden and become denser. The disorder can cause osteosclerosis. The estimated prevalence of osteopetrosis is 1 in 100,000 to 500,000. It presents in two major clinical forms-a benign autosomal dominant form and a malignant autosomal recessive form. The autosomal dominant adult (benign) form is associated with few, if any, symptoms, and the autosomal recessive infantile (malignant) form is typically fatal during infancy or early childhood if untreated [1]. A rarer autosomal recessive (intermediate) form presents during childhood with some signs and symptoms of malignant osteopetrosis.
  • A Molecular and Genetic Analysis of Otosclerosis

    A Molecular and Genetic Analysis of Otosclerosis

    A molecular and genetic analysis of otosclerosis Joanna Lauren Ziff Submitted for the degree of PhD University College London January 2014 1 Declaration I, Joanna Ziff, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Where work has been conducted by other members of our laboratory, this has been indicated by an appropriate reference. 2 Abstract Otosclerosis is a common form of conductive hearing loss. It is characterised by abnormal bone remodelling within the otic capsule, leading to formation of sclerotic lesions of the temporal bone. Encroachment of these lesions on to the footplate of the stapes in the middle ear leads to stapes fixation and subsequent conductive hearing loss. The hereditary nature of otosclerosis has long been recognised due to its recurrence within families, but its genetic aetiology is yet to be characterised. Although many familial linkage studies and candidate gene association studies to investigate the genetic nature of otosclerosis have been performed in recent years, progress in identifying disease causing genes has been slow. This is largely due to the highly heterogeneous nature of this condition. The research presented in this thesis examines the molecular and genetic basis of otosclerosis using two next generation sequencing technologies; RNA-sequencing and Whole Exome Sequencing. RNA–sequencing has provided human stapes transcriptomes for healthy and diseased stapes, and in combination with pathway analysis has helped identify genes and molecular processes dysregulated in otosclerotic tissue. Whole Exome Sequencing has been employed to investigate rare variants that segregate with otosclerosis in affected families, and has been followed by a variant filtering strategy, which has prioritised genes found to be dysregulated during RNA-sequencing.
  • Diagnosis and Treatment of Intramedullary Osteosclerosis

    Diagnosis and Treatment of Intramedullary Osteosclerosis

    Abe et al. BMC Musculoskeletal Disorders (2020) 21:762 https://doi.org/10.1186/s12891-020-03758-5 CASE REPORT Open Access Diagnosis and treatment of intramedullary osteosclerosis: a report of three cases and literature review Kensaku Abe, Norio Yamamoto, Katsuhiro Hayashi, Akihiko Takeuchi* , Shinji Miwa, Kentaro Igarashi, Takashi Higuchi, Yuta Taniguchi, Hirotaka Yonezawa, Yoshihiro Araki, Sei Morinaga, Yohei Asano and Hiroyuki Tsuchiya Abstract Background: Intramedullary osteosclerosis (IMOS) is a rare condition without specific radiological findings except for the osteosclerotic lesion and is not associated with family history and infection, trauma, or systemic illness. Although the diagnosis of IMOS is confirmed after excluding other osteosclerotic lesions, IMOS is not well known because of its rarity and no specific feature. Therefore, these situations might result in delayed diagnosis. Hence, this case report aimed to investigate three cases of IMOS and discuss imaging findings and clinical outcomes. Case presentation: All three cases were examined between 2015 and 2019. The location of osteosclerotic lesions were femoral diaphyses in the 60-year-old man (Case 1) and 41-year-old woman (Case 2) and tibial diaphysis in the 44-year-old woman (Case 3). All cases complained of severe pain and showed massive diaphyseal osteosclerotic lesions in plain radiograms and computed tomography (CT) scans. Cases 2 and 3 were examined using the triphasic bone scan, and a fusiform-shaped intense area of the tracer uptake on delayed bone image was detected in both cases without (Case 2) or slightly increased vascularity (Case 3) on the blood pool image, which was reported as a specific finding of IMOS.
  • Genetic Causes and Underlying Disease Mechanisms in Early-Onset Osteoporosis

    Genetic Causes and Underlying Disease Mechanisms in Early-Onset Osteoporosis

    From DEPARTMENT OF MOLECULAR MEDICINE AND SURGERY Karolinska Institutet, Stockholm, Sweden GENETIC CAUSES AND UNDERLYING DISEASE MECHANISMS IN EARLY-ONSET OSTEOPOROSIS ANDERS KÄMPE Stockholm 2020 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by Eprint AB 2020 © Anders Kämpe, 2020 ISBN 978-91-7831-759-2 Genetic causes and underlying disease mechanisms in early-onset osteoporosis THESIS FOR DOCTORAL DEGREE (Ph.D.) By Anders Kämpe Principal Supervisor: Opponent: Professor Outi Mäkitie Professor André Uitterlinden Karolinska Institutet Erasmus Medical Centre, Rotterdam Department of Molecular Medicine and Surgery Department of Internal Medicine Laboratories Genetic Laboratory / Human Genomics Facility (HuGe-F) Co-supervisor(s): Examination Board: Associate Professor Anna Lindstrand Professor Marie-Louise Bondeson Karolinska Institutet Uppsala University Department of Molecular Medicine and Surgery Department of Immunology, Genetics and Pathology Associate Professor Giedre Grigelioniene Professor Göran Andersson Karolinska Institutet Karolinska Institutet Department of Molecular Medicine and Surgery Department of Laboratory Medicine Professor Ann Nordgren Minna Pöyhönen Karolinska Institutet University of Helsinki Department of Molecular Medicine and Surgery Department of Medical Genetics Associate Professor Hong Jiao Karolinska Institutet Department of Biosciences and Nutrition ABSTRACT Adult-onset osteoporosis is a disorder that affects a significant proportion of the elderly population worldwide and entails a substantial disease burden for the affected individuals. Childhood-onset osteoporosis is a rare condition often associating with a severe bone disease and recurrent fractures already in early childhood. Both childhood-onset and adult-onset osteoporosis have a large genetic component, but in children the disorder is usually genetically less complex and often caused by a single gene variant.
  • Osteomalacia and Osteoporosis D

    Osteomalacia and Osteoporosis D

    Postgrad. med.J. (August 1968) 44, 621-625. Postgrad Med J: first published as 10.1136/pgmj.44.514.621 on 1 August 1968. Downloaded from Osteomalacia and osteoporosis D. B. MORGAN Department of Clinical Investigation, University ofLeeds OSTEOMALACIA and osteoporosis are still some- in osteomalacia is an increase in the alkaline times confused because both diseases lead to a phosphatase activity in the blood (SAP); there deficiency of calcium which can be detected on may also be a low serum phosphorus or a low radiographs of the skeleton. serum calcium. This lack of calcium is the only feature Our experience with the biopsy of bone is that common to the two diseases which are in all a large excess of uncalcified bone tissue (osteoid), other ways easily distinguishable. which is the classic histological feature of osteo- malacia, is only found in patients with the other Osteomalacia typical features of the disease, in particular the Osteomalacia will be discussed first, because it clinical ones (Morgan et al., 1967a). Whether or is a clearly defined disease which can be cured. not more subtle histological techniques will detect Osteomalacia is the result of an imbalance be- earlier stages of the disease remains to be seen. tween the supply of and the demand for vitamin Bone pains, muscle weakness, Looser's zones, D. The the following description of disease is raised SAP and low serum phosphate are the Protected by copyright. based on our experience of twenty-two patients most reliable aids to the diagnosis of osteomalacia, with osteomalacia after gastrectomy; there is no and approximately in that order.
  • Skeletal Dysplasias

    Skeletal Dysplasias

    Skeletal Dysplasias North Carolina Ultrasound Society Keisha L.B. Reddick, MD Wilmington Maternal Fetal Medicine Development of the Skeleton • 6 weeks – vertebrae • 7 weeks – skull • 8 wk – clavicle and mandible – Hyaline cartilage • Ossification – 7-12 wk – diaphysis appears – 12-16 wk metacarpals and metatarsals – 20+ wk pubis, calus, calcaneus • Visualization of epiphyseal ossification centers Epidemiology • Overall 9.1 per 1000 • Lethal 1.1 per 10,000 – Thanatophoric 1/40,000 – Osteogenesis Imperfecta 0.18 /10,000 – Campomelic 0.1 /0,000 – Achondrogenesis 0.1 /10,000 • Non-lethal – Achondroplasia 15 in 10,000 Most Common Skeletal Dysplasia • Thantophoric dysplasia 29% • Achondroplasia 15% • Osteogenesis imperfecta 14% • Achondrogenesis 9% • Campomelic dysplasia 2% Definition/Terms • Rhizomelia – proximal segment • Mezomelia –intermediate segment • Acromelia – distal segment • Micromelia – all segments • Campomelia – bowing of long bones • Preaxial – radial/thumb or tibial side • Postaxial – ulnar/little finger or fibular Long Bone Segments Counseling • Serial ultrasound • Genetic counseling • Genetic testing – Amniocentesis • Postnatal – Delivery center – Radiographs Assessment • Which segment is affected • Assessment of distal extremities • Any curvatures, fracture or clubbing noted • Are metaphyseal changes present • Hypoplastic or absent bones • Assessment of the spinal canal • Assessment of thorax. Skeletal Dysplasia Lethal Non-lethal • Thanatophoric • Achondroplasia • OI type II • OI type I, III, IV • Achondrogenesis • Hypochondroplasia
  • Inherited Renal Tubulopathies—Challenges and Controversies

    Inherited Renal Tubulopathies—Challenges and Controversies

    G C A T T A C G G C A T genes Review Inherited Renal Tubulopathies—Challenges and Controversies Daniela Iancu 1,* and Emma Ashton 2 1 UCL-Centre for Nephrology, Royal Free Campus, University College London, Rowland Hill Street, London NW3 2PF, UK 2 Rare & Inherited Disease Laboratory, London North Genomic Laboratory Hub, Great Ormond Street Hospital for Children National Health Service Foundation Trust, Levels 4-6 Barclay House 37, Queen Square, London WC1N 3BH, UK; [email protected] * Correspondence: [email protected]; Tel.: +44-2381204172; Fax: +44-020-74726476 Received: 11 February 2020; Accepted: 29 February 2020; Published: 5 March 2020 Abstract: Electrolyte homeostasis is maintained by the kidney through a complex transport function mostly performed by specialized proteins distributed along the renal tubules. Pathogenic variants in the genes encoding these proteins impair this function and have consequences on the whole organism. Establishing a genetic diagnosis in patients with renal tubular dysfunction is a challenging task given the genetic and phenotypic heterogeneity, functional characteristics of the genes involved and the number of yet unknown causes. Part of these difficulties can be overcome by gathering large patient cohorts and applying high-throughput sequencing techniques combined with experimental work to prove functional impact. This approach has led to the identification of a number of genes but also generated controversies about proper interpretation of variants. In this article, we will highlight these challenges and controversies. Keywords: inherited tubulopathies; next generation sequencing; genetic heterogeneity; variant classification. 1. Introduction Mutations in genes that encode transporter proteins in the renal tubule alter kidney capacity to maintain homeostasis and cause diseases recognized under the generic name of inherited tubulopathies.
  • Metabolic Bone Disease 5

    Metabolic Bone Disease 5

    g Metabolic Bone Disease 5 Introduction, 272 History and examination, 275 Osteoporosis, 283 STRUCTURE AND FUNCTION, 272 Investigation, 276 Paget’s disease of bone, 288 Structure of bone, 272 Management, 279 Hyperparathyroidism, 290 Function of bone, 272 DISEASES AND THEIR MANAGEMENT, 280 Hypercalcaemia of malignancy, 293 APPROACH TO THE PATIENT, 275 Rickets and osteomalacia, 280 Hypocalcaemia, 295 Introduction Calcium- and phosphate-containing crystals: set in a structure• similar to hydroxyapatite and deposited in holes Metabolic bone diseases are a heterogeneous group of between adjacent collagen fibrils, which provide rigidity. disorders characterized by abnormalities in calcium At least 11 non-collagenous matrix proteins (e.g. osteo- metabolism and/or bone cell physiology. They lead to an calcin,• osteonectin): these form the ground substance altered serum calcium concentration and/or skeletal fail- and include glycoproteins and proteoglycans. Their exact ure. The most common type of metabolic bone disease in function is not yet defined, but they are thought to be developed countries is osteoporosis. Because osteoporosis involved in calcification. is essentially a disease of the elderly, the prevalence of this condition is increasing as the average age of people Cellular constituents in developed countries rises. Osteoporotic fractures may lead to loss of independence in the elderly and is imposing Mesenchymal-derived osteoblast lineage: consist of an ever-increasing social and economic burden on society. osteoblasts,• osteocytes and bone-lining cells. Osteoblasts Other pathological processes that affect the skeleton, some synthesize organic matrix in the production of new bone. of which are also relatively common, are summarized in Osteoclasts: derived from haemopoietic precursors, Table 3.20 (see Chapter 4).
  • MICHIGAN BIRTH DEFECTS REGISTRY Cytogenetics Laboratory Reporting Instructions 2002

    MICHIGAN BIRTH DEFECTS REGISTRY Cytogenetics Laboratory Reporting Instructions 2002

    MICHIGAN BIRTH DEFECTS REGISTRY Cytogenetics Laboratory Reporting Instructions 2002 Michigan Department of Community Health Community Public Health Agency and Center for Health Statistics 3423 N. Martin Luther King Jr. Blvd. P. O. Box 30691 Lansing, Michigan 48909 Michigan Department of Community Health James K. Haveman, Jr., Director B-274a (March, 2002) Authority: P.A. 236 of 1988 BIRTH DEFECTS REGISTRY MICHIGAN DEPARTMENT OF COMMUNITY HEALTH BIRTH DEFECTS REGISTRY STAFF The Michigan Birth Defects Registry staff prepared this manual to provide the information needed to submit reports. The manual contains copies of the legislation mandating the Registry, the Rules for reporting birth defects, information about reportable and non reportable birth defects, and methods of reporting. Changes in the manual will be sent to each hospital contact to assist in complete and accurate reporting. We are interested in your comments about the manual and any suggestions about information you would like to receive. The Michigan Birth Defects Registry is located in the Office of the State Registrar and Division of Health Statistics. Registry staff can be reached at the following address: Michigan Birth Defects Registry 3423 N. Martin Luther King Jr. Blvd. P.O. Box 30691 Lansing MI 48909 Telephone number (517) 335-8678 FAX (517) 335-9513 FOR ASSISTANCE WITH SPECIFIC QUESTIONS PLEASE CONTACT Glenn E. Copeland (517) 335-8677 Cytogenetics Laboratory Reporting Instructions I. INTRODUCTION This manual provides detailed instructions on the proper reporting of diagnosed birth defects by cytogenetics laboratories. A report is required from cytogenetics laboratories whenever a reportable condition is diagnosed for patients under the age of two years.
  • SKELETAL DYSPLASIA Dr Vasu Pai

    SKELETAL DYSPLASIA Dr Vasu Pai

    SKELETAL DYSPLASIA Dr Vasu Pai Skeletal dysplasia are the result of a defective growth and development of the skeleton. Dysplastic conditions are suspected on the basis of abnormal stature, disproportion, dysmorphism, or deformity. Diagnosis requires Simple measurement of height and calculation of proportionality [<60 inches: consideration of dysplasia is appropriate] Dysmorphic features of the face, hands, feet or deformity A complete physical examination Radiographs: Extremities and spine, skull, Pelvis, Hand Genetics: the risk of the recurrence of the condition in the family; Family evaluation. Dwarf: Proportional: constitutional or endocrine or malnutrition Disproportion [Trunk: Extremity] a. Height < 42” Diastrophic Dwarfism < 48” Achondroplasia 52” Hypochondroplasia b. Trunk-extremity ratio May have a normal trunk and short limbs (achondroplasia), Short trunk and limbs of normal length (e.g., spondylo-epiphyseal dysplasia tarda) Long trunk and long limbs (e.g., Marfan’s syndrome). c. Limb-segment ratio Normal: Radius-Humerus ratio 75% Tibia-Femur 82% Rhizomelia [short proximal segments as in Achondroplastics] Mesomelia: Dynschondrosteosis] Acromelia [short hands and feet] RUBIN CLASSIFICATION 1. Hypoplastic epiphysis ACHONDROPLASTIC Autosomal Dominant: 80%; 0.5-1.5/10000 births Most common disproportionate dwarfism. Prenatal diagnosis: 18 weeks by measuring femoral and humeral lengths. Abnormal endochondral bone formation: zone of hypertrophy. Gene defect FGFR fibroblast growth factor receptor 3 . chromosome 4 Rhizomelic pattern, with the humerus and femur affected more than the distal extremities; Facies: Frontal bossing; Macrocephaly; Saddle nose Maxillary hypoplasia, Mandibular prognathism Spine: Lumbar lordosis and Thoracolumbar kyphosis Progressive genu varum and coxa valga Wedge shaped gaps between 3rd and 4th fingers (trident hands) Trident hand 50%, joint laxity Pathology Lack of columnation Bony plate from lack of growth Disorganized metaphysis Orthopaedics 1.
  • Dwarfism Awareness

    Dwarfism Awareness

    LPA Mission Statement LPA is dedicated to improving the quality of life for people with dwarfism throughout their lives, while celebrating with great pride little people’s contribution to social diversity. LPA strives to bring solutions and global For More Information awareness to the prominent issues affecting individuals of Contact LPA short stature and their families. Toll Free…(888) LPA-2001 Direct....(714) 368-3689 Fax…..(707) 721-1896 Dwarfism Check out our website at Awareness www.lpaonline.org A Community Outreach Program 617 Broadway #518 Sponsored by Little People of America Sonoma, CA 95476 LPA is a non-profit tax exempt 501(c)3 organization funded by individual donations. Contact LPA to help. Dwarfism - Facts and Fiction Mythbusters Terminology Bodies come in all shapes and sizes. There are about 400 People with dwarfism are not magical; they do not fly, nor are Preferred terminology is a personal decision, but different types of dwarfism. Each type of dwarfism is they leprechauns, elves, fairies or any other mythological commonly accepted terms are - short stature, different than the other. Many types of dwarfism have creature. They are people - people whose bones happen to dwarfism, little person, dwarf. And we say some medical complications but most people have an grow differently than yours. That is all. "average-height" instead of "normal height". average lifespan, being productive members of society. People with dwarfism do not all know each People with dwarfism are different, yes, but not Eighty percent of people with dwarfism have average- other or look alike, nor are there towns "abnormal". height parents and siblings.