DOCSLIB.ORG

Current Concepts Review

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Current Concepts Review CURRENT CONCEPTS REVIEW GENES AND ORTHOPEDICS : FROM GENE TO CLINIC AND VICE VERSA Ph. DEBEER1,2,3, L. DE SMET1, W. J. M. VAN DE VEN3, G. FABRY1, J.-P. FRYNS2 Recent advances in molecular biology have greatly identify novel genes. Recent technical advances in helped in understanding the mechanisms involved in molecular biology and the completion of the normal skeletal morphogenesis. Multiple genes Human Genome Project (38, 61), which involved involved in normal skeletal development have been sequencing the three million base pairs of the identified, but several others still await discovery. human genome, have significantly facilitated the Mutations in these genes are often responsible for the possibility to locate and identify genes responsible congenital skeletal malformations that we see in the orthopedic clinics. In this overview we would like to for normal skeletal development. Further characte- emphasize the importance of the interaction between rization of these genes and elucidation of the func- orthopaedic surgeons, molecular biologists and tion of the corresponding proteins will undoubted- geneticists. ly provide us with more information regarding their role in normal limb- and skeletal development. Keywords : skeletal development ; congenital orthope- In this review, we present a brief overview of the dic malformations. current knowledge of the molecular aspects of Mots-clés : développement du squelette ; malformations orthopédiques. skeletal disease and illustrate how the recent advances in genetics may have practical implica- tions for patients with orthopaedic problems. INTRODUCTION Etiology of congenital malformations The embryonic development of the skeleton and Over 6000 human disorders exhibit simple gene limbs is an intriguing and complex process, which unifactorial or Mendelian inheritance. A disorder involves a cascade of molecular interactions. More determined by a gene on an autosome is said to specifically, differentiation, proliferation and pro- show autosomal inheritance, whereas a disorder grammed cell death play an important role. Much determined by a gene on one of the sex chromo- of what we know about the general mechanism underlying skeletal morphogenesis is the result of animal studies. The consequences of spontaneous ———————— 1 or induced mutations in the fruitfly (Drosophila Department of Orthopedics, University Hospital Pellenberg, Weligerveld 1, B-3212 Lubbeek (Pellenberg), melanogaster), worm (Caenorhabditis elegans), Belgium. zebra fish (Danio rerio), frog (Xenopus laevis), 2 Centre for Human Genetics, Herestraat 49, chicken and mouse have lead to the identification B-3000 Leuven, Belgium. of a multitude of genes involved in normal skeletal 3 Laboratory for Molecular Oncology, Herestraat 49, development (39, 41, 44, 45). Congenital deforma- B-3000 Leuven, Belgium. tions in humans, isolated or as part of a syndrome, Correspondence and reprints : Ph. Debeer, Department of Orthopaedic Surgery, U.Z. Pellenberg, Weligerveld 1, also provide us with the unique opportunity to B-3212 Lubbeek (Pellenberg), Belgium. Acta Orthopædica Belgica, Vol. 68 - 3 - 2002 204 PH. DEBEER, L. DE SMET, W. J. M. VA N D E V E N , G. FABRY, J.-P. FRYNS somes is said to show sex-linked inheritance. A tal malformation occasionally reveal a chromo- dominant trait manifests itself in a heterozygote, a somal aberration. These include abnormalities in person possessing both the abnormal or mutant chromosome number (aneuploidies, e.g. trisomy allele and the normal allele. The clinical features in 13 and trisomy 21, which give rise to polydacty- dominant traits can vary from person to person. ly and brachydactyly respectively) or abnormali- This is known as variable expressivity. In some ties in chromosome structure (for example the individuals of families with autosomal dominant ring chromosome 13 syndrome which is accom- traits, the presence of the mutation can go unde- panied by absence of the thumb). tected (‘skip a generation’), which is known as 4. The great majority of congenital malformations reduced penetrance. In autosomal dominant disor- however, are caused by a combination of genetic ders an affected person usually has an affected and environmental factors. In these cases parent. Sometimes a disorder can appear in an indi- patients have a genetic liability to develop a vidual whose parents (and all the previous genera- disease, but an environmental factor is also tions) are unaffected. This sudden appearance of a necessary. condition due to a mistake occurring in the trans- We will further focus our attention on congenital mission of a gene is called a new mutation (de novo disorders with an underlying genetic defect. mutation). Recessive disorders are only manifest when the mutant allele is present in a double dose How can we find novel genes involved in skeletal (homozygosity). Both parents of the affected person malformations ? are obligate heterozygous for the mutation. They are perfectly healthy carriers. Many disorders Several approaches can be used in order to detect demonstrate a type of inheritance that is not similar genes involved in human disease (11, 12). Some- to any recognised Mendelian pattern (for instance times information about the underlying biochemi- congenital dislocation of the hip). This pattern of cal defect is used. Using a functional cloning inheritance is referred to as multifactorial. Both approach, the identification of a gene is based on genes and environmental factors play a role in these pre-existing information about the underlying bio- disorders. chemical defect. No reference is made to any chro- When searching for the possible causes of con- mosomal map position or sequence information. genital malformations, four categories must be Positional cloning assumes no functional informa- considered. tion and must locate the responsible genes on the 1. Sometimes, a clear exogenous insult can be basis of map position. In a first step, linkage analy- identified as the main causative factor. Examples sis of multiple affected families can assist in map- include the limb anomalies caused by thalido- ping the disease gene on a specific chromosome. mide, congenital malformations caused by The identification of patients with chromosomal maternal illness (infections, hypertension, dia- aberrations (chromosomal deletions, inversions, betes, toxemia) and transverse limb deficiencies translocations, duplications,...) is often of great caused by early chorion villus sampling with help. After mapping the cytogenetic aberration to fetal vascular shock. Poland syndrome (unilater- its correct location on the chromosome, the candi- al symbrachydactyly with ipsilateral aplasia of date interval is narrowed down until the gene is the pectoralis major) is probably due to a prima- identified. The genetic tools used mainly consist of ry defect in the development of the subclavian previously constructed chromosomal maps and artery. sequence information. All these data can be found 2. In some Mendelian inherited conditions, a single at various sites on the World Wide Web. The com- major gene can be identified, for example the pletion of the Human Genome Project greatly faci- HOXD13 mutations in synpolydactyly (1, 47). litates the search for genes involved in human 3. Chromosome studies in patients with a congeni- disease. The candidate gene approach makes use of Acta Orthopædica Belgica, Vol. 68 - 3 - 2002 GENES AND ORTHOPEDICS 205 information of already known genes. Features of Foot-Genital-Syndrome (42, 43)). Figure 1 illus- the disease are compared with those of the gene trates how currently all the available data and tech- and, depending on the results of this comparison, a niques can be combined in searching for human specific gene is considered a good candidate or not. disease genes. There is a clear interplay between Mutation analysis of this gene in affected patients clinical work, computer analysis (“cyber cloning”) may prove that this gene is indeed responsible for and laboratory benchwork. It is obvious that the the observed phenotype. The positional candidate advances in the Human Genome Project greatly gene approach combines the two latter methods. speed up this approach. First the disease locus is mapped to the correct chromosomal region, followed by a search of this Molecular genetics of skeletal disease : an interval to see whether any functionally interesting overview candidate genes have been positioned there. In our search for genes involved in skeletal malforma- A detailed description of all the disorders given tions, information derived from other species is below can be found in the OMIM database (Online often of great help. Several mouse models with dis- Mendelian Inheritance in Man ; http://www.ncbi. tinct phenotypes have been described (39, 41). nlm.nih.gov/Omim/). Table 1 gives an overview of Sometimes a human limb deformity shows great some congenital malformations with orthopedic resemblance with that of a previously described implications. The underlying genetic defect, if mouse. If the genetic defect in the mouse is known, known, is indicated together with the mode of identification of its human counterpart is possible inheritance (AD = autosomal dominant ; AR= auto- (for example the identification of hoxa13 mutations somal recessive) and the OMIM number. Neuro- in the hypodactyly mouse and the subsequent iden- muscular and metabolic disorders were not in- tification of human HOXA13 mutations in Hand- cluded. Fig. 1. — This flowchart illustrates the important interplay between
Load more

Recommended publications
  • Genes in Eyecare Geneseyedoc 3 W.M
    Genes in Eyecare geneseyedoc 3 W.M. Lyle and T.D. Williams 15 Mar 04 This information has been gathered from several sources; however, the principal source is V. A. McKusick’s Mendelian Inheritance in Man on CD-ROM. Baltimore, Johns Hopkins University Press, 1998. Other sources include McKusick’s, Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore. Johns Hopkins University Press 1998 (12th edition). http://www.ncbi.nlm.nih.gov/Omim See also S.P.Daiger, L.S. Sullivan, and B.J.F. Rossiter Ret Net http://www.sph.uth.tmc.edu/Retnet disease.htm/. Also E.I. Traboulsi’s, Genetic Diseases of the Eye, New York, Oxford University Press, 1998. And Genetics in Primary Eyecare and Clinical Medicine by M.R. Seashore and R.S.Wappner, Appleton and Lange 1996. M. Ridley’s book Genome published in 2000 by Perennial provides additional information. Ridley estimates that we have 60,000 to 80,000 genes. See also R.M. Henig’s book The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, published by Houghton Mifflin in 2001 which tells about the Father of Genetics. The 3rd edition of F. H. Roy’s book Ocular Syndromes and Systemic Diseases published by Lippincott Williams & Wilkins in 2002 facilitates differential diagnosis. Additional information is provided in D. Pavan-Langston’s Manual of Ocular Diagnosis and Therapy (5th edition) published by Lippincott Williams & Wilkins in 2002. M.A. Foote wrote Basic Human Genetics for Medical Writers in the AMWA Journal 2002;17:7-17. A compilation such as this might suggest that one gene = one disease.
    [Show full text]
  • RD-Action Matchmaker – Summary of Disease Expertise Recorded Under
    Summary of disease expertise recorded via RD-ACTION Matchmaker under each Thematic Grouping and EURORDIS Members’ Thematic Grouping Thematic Reported expertise of those completing the EURORDIS Member perspectives on Grouping matchmaker under each heading Grouping RD Thematically Rare Bone Achondroplasia/Hypochondroplasia Achondroplasia Amelia skeletal dysplasia’s including Achondroplasia/Growth hormone cleidocranial dysostosis, arthrogryposis deficiency/MPS/Turner Brachydactyly chondrodysplasia punctate Fibrous dysplasia of bone Collagenopathy and oncologic disease such as Fibrodysplasia ossificans progressive Li-Fraumeni syndrome Osteogenesis imperfecta Congenital hand and fore-foot conditions Sterno Costo Clavicular Hyperostosis Disorders of Sex Development Duchenne Muscular Dystrophy Ehlers –Danlos syndrome Fibrodysplasia Ossificans Progressiva Growth disorders Hypoparathyroidism Hypophosphatemic rickets & Nutritional Rickets Hypophosphatasia Jeune’s syndrome Limb reduction defects Madelung disease Metabolic Osteoporosis Multiple Hereditary Exostoses Osteogenesis imperfecta Osteoporosis Paediatric Osteoporosis Paget’s disease Phocomelia Pseudohypoparathyroidism Radial dysplasia Skeletal dysplasia Thanatophoric dwarfism Ulna dysplasia Rare Cancer and Adrenocortical tumours Acute monoblastic leukaemia Tumours Carcinoid tumours Brain tumour Craniopharyngioma Colon cancer, familial nonpolyposis Embryonal tumours of CNS Craniopharyngioma Ependymoma Desmoid disease Epithelial thymic tumours in
    [Show full text]
  • Appendix A: Organisation of a Craniofacial Unit
    Appendix A: Organisation of a Craniofacial Unit The requirements of patients with craniofacial abnormalities are very complex and demand a multidisciplinary approach. Many body systems are affected, and every detail of patient management has to be given due attention. Care begins at birth and continues until the patient and his family have been relieved of the burden of the anomaly. A team is needed, capable of delivering expert patient care, and representative of all the relevant disciplines. Data, in the form of histories, physical examinations, and special investigations, are needed in planning treatment, and such data should be used to the maximum scientific effect, to improve present methods of management, still far from satisfactory, and to expand knowledge of the biology of cranial growth and its disorders. Craniofacial Units Sporadic craniofacial procedures performed by a surgeon on an irregular basis invite disaster. Tessier (1971a) estimated that each craniofacial centre should serve a population of 10 to 20 million people, provided that the team performed only craniofacial surgery and treated at least 50 new cases annually. As a consequence of Tessier's example and teaching there are now centres of acknowledged excellence in Paris and Nancy, attracting patients not only from France but also from North Africa and elsewhere. In North America there are now important craniofacial centres in Philadelphia, New York, Boston, Toronto, and Mexico City. Munro (1975) proposed that North America should be divided into seven regions, six for the United States and one for Canada, each serving populations of 20 to 40 million people. He believed that such centres would allow a concentration of multidisciplinary skills and accumulation of experience in the treatment of craniofacial anomalies.
    [Show full text]
  • 349 D.R. Laub Jr. (Ed.), Congenital Anomalies of the Upper
    Index A dermatological anomalies , 182 Abductor digiti minimi (ADM) transfer , 102–103 skeletal abnormalities , 182 Abductor pollicis brevis (APB) , 186–187 upper extremity anomalies , 182, 183 ABS. See Amniotic band syndrome (ABS) visceral anomalies , 182 Achondroplasia defi nition of , 179 classifi cation/characterization , 338 description , 32, 33 defi nition of , 337–338 epidemiology of , 181 genetics , 338 genetics and embryology management , 338 molecular etiology , 180 Acrocephalosyndactyly syndrome , 32, 33, 179 prenatal diagnosis , 180–181 Acrosyndactyly repair, ABS , 300–302 molecular basis of , 180 Adactylic group IV symbrachydactyly , 129, 131 postoperative care and complications , 187 Al-Awadi syndrome , 154 treatment Amniotic band syndrome (ABS) APB release , 186–187 acrosyndactyly repair , 300–302 border digits syndactylies , 184 anesthesia concerns of fi rst web space release , 186 induction and maintenance of anesthesia , 43 patient age , 183 postoperative concerns , 43 secondary revisions , 187 preoperative preparation , 42–43 symphalangism , 184 classifi cation , 298 syndactyly ( see Syndactyly) clinical presentation thumb radial clinodactyly , 186–187 acrosyndactyly , 297–298 type II apert hand , 187–188 digital malformation , 297 Apical ectodermal ridge (AER) , 3–5 distal skeletal bones tapering , 297–298 Arthrogryposis , 210 hand deformity , 297 classic arthrogryposis , 305–306, 308 complications , 302 classifi cation , 305, 306 constriction band release defi nition of , 229, 230, 305 Upton’s technique , 299, 301 de-rotation osteotomy, shoulder , 308, 309 z-plasty , 299–300 distal , 230–231 ( see Distal arthrogryposis) diagnosis of , 296 elbow treatment digital hypoplasia reconstruction , 302 muscle transfers , 310–311 etiology of , 295–296 nonoperative management , 308 preoperative considerations , 299 posterior elbow capsular release , 309 treatment , 299 radial head dislocations , 311 Amniotic constriction band syndrome.
    [Show full text]
  • Molecular Mechanisms in Calvarial Bone and Suture Development
    Molecular Mechanisms in Calvarial Bone and Suture Development David Rice Department of Orthodontics and Pedodontics, Institute of Dentistry, and, Developmental Biology Programme, Institute of Biotechnology, University of Helsinki, Finland. Academic Dissertation To be discussed publicly with the permission of the Faculty of Medicine of the University of Helsinki, in auditorium 1041, Viikki Biocenter 2 on 5th November 1999, at 12 noon. Helsinki 1999 Supervised by: Professor Irma Thesleff, University of Helsinki, Finland. Reviewed by: Professor Seppo Vainio, University of Oulu, Finland. and Professor Kalervo Väänänen, University of Turku, Finland. Opponent: Assistant Professor Lynne Opperman, Baylor School of Dentistry, Texas A & M University, U.S.A. ISBN 951-45-8960-2 (PDF version) Helsinki 1999 Helsingin yliopiston verkkojulkaisut http://ethesis.helsinki.fi/ 2 CONTENTS 3DJH /LVW RI 2ULJLQDO 3XEOLFDWLRQV 5 $EEUHYLDWLRQV 6 6XPPDU\ 7 5HYLHZ RI WKH /LWHUDWXUH 9 %RQH 'HYHORSPHQW DQG *URZWK 9 Origin and patterning of the craniofacial skeleton 9 Mesenchymal condensations 9 Intramembraneous ossification 10 Endochondral ossification 11 &HOOXODU %LRORJ\ RI %RQH 11 Osteoblasts, stromal cells and osteocytes 13 Osteoclasts 18 Proliferation of bone cells 22 Proliferation during calvarial bone and suture development 22 Apoptosis during embryogenesis 23 Apoptosis during bone and suture development 24 'HYHORSPHQW RI WKH &DOYDULD 24 Developmental anatomy 24 Sutures and fontanelles 25 Suture morphology 26 Suture closure 27 Suture position 27 Sutural growth
    [Show full text]
  • Review Article Cleidocranial Dysplasia: Clinical and Molecular Genetics
    J Med Genet 1999;36:177–182 177 Review article Cleidocranial dysplasia: clinical and molecular genetics Stefan Mundlos Abstract Chinese named Arnold, was probably de- Cleidocranial dysplasia (CCD) (MIM scribed by Jackson.6 He was able to trace 356 119600) is an autosomal dominant skeletal members of this family of whom 70 were dysplasia characterised by abnormal aVected with the “Arnold Head”. CCD was clavicles, patent sutures and fontanelles, originally thought to involve only bones of supernumerary teeth, short stature, and a membranous origin. More recent and detailed variety of other skeletal changes. The dis- clinical investigations have shown that CCD is ease gene has been mapped to chromo- a generalised skeletal dysplasia aVecting not some 6p21 within a region containing only the clavicles and the skull but the entire CBFA1, a member of the runt family of skeleton. CCD was therefore considered to be transcription factors. Mutations in the a dysplasia rather than a dysostosis.7 Skeletal CBFA1 gene that presumably lead to syn- abnormalities commonly found include cla- thesis of an inactive gene product were vicular aplasia/hypoplasia, bell shaped thorax, identified in patients with CCD. The func- enlarged calvaria with frontal bossing and open tion of CBFA1 during skeletal develop- fontanelles, Wormian bones, brachydactyly ment was further elucidated by the with hypoplastic distal phalanges, hypoplasia of generation of mutated mice in which the the pelvis with widened symphysis pubis, Cbfa1 gene locus was targeted. Loss of one severe dental anomalies, and short stature. The Cbfa1 allele (+/-) leads to a phenotype very changes suggest that the gene responsible is not similar to human CCD, featuring hypo- only active during early development, as plasia of the clavicles and patent fonta- implied by changes in the shape or number of nelles.
    [Show full text]
  • Statistical Analysis Plan
    Cover Page for Statistical Analysis Plan Sponsor name: Novo Nordisk A/S NCT number NCT03061214 Sponsor trial ID: NN9535-4114 Official title of study: SUSTAINTM CHINA - Efficacy and safety of semaglutide once-weekly versus sitagliptin once-daily as add-on to metformin in subjects with type 2 diabetes Document date: 22 August 2019 Semaglutide s.c (Ozempic®) Date: 22 August 2019 Novo Nordisk Trial ID: NN9535-4114 Version: 1.0 CONFIDENTIAL Clinical Trial Report Status: Final Appendix 16.1.9 16.1.9 Documentation of statistical methods List of contents Statistical analysis plan...................................................................................................................... /LQN Statistical documentation................................................................................................................... /LQN Redacted VWDWLVWLFDODQDO\VLVSODQ Includes redaction of personal identifiable information only. Statistical Analysis Plan Date: 28 May 2019 Novo Nordisk Trial ID: NN9535-4114 Version: 1.0 CONFIDENTIAL UTN:U1111-1149-0432 Status: Final EudraCT No.:NA Page: 1 of 30 Statistical Analysis Plan Trial ID: NN9535-4114 Efficacy and safety of semaglutide once-weekly versus sitagliptin once-daily as add-on to metformin in subjects with type 2 diabetes Author Biostatistics Semaglutide s.c. This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant parties.This
    [Show full text]
  • Jordan Cleidocranial Dysostosis Case Study
    Case Study: Jordan Conditions Treated Cleidocranial Dysostosis Age Range During Treatment 13 Years – 14 Years David S. Feldman, MD Chief of Pediatric Orthopedic Surgery Professor of Orthopedic Surgery & Pediatrics NYU Langone Medical Center & NYU Hospital for Joint Diseases BACKGROUND Jordan was delivered via c-section in a twin birth and spent two days in NICU. He was born with a few muscular and skeletal issues which included low muscle tone, absent clavicles, and congenital kyphosis (spinal curve that bows or rounds the back). Jordan was later diagnosed with cleidocranial dysostosis, a rare hereditary congenital disorder that runs in his family which causes teeth and bones (especially in the upper torso) to develop abnormally. Jordan’s development was followed by an orthopedic doctor and at the age of 11 his parent’s took the additional proactive step of having a chiropractor fit him for a SpineCor Brace which he wore at all times except for when bathing. During a follow-up visit at age 13, his orthopedic doctor noticed that his spinal curve was progressing and discussed surgical options with Jordan’s family. EVALUATION Jordan visited my office for a second opinion on his spine. During his initial physical examination I found that while his clavicles were present they were not connected. His spine deviated from the midline of his body but there were no skin markings, masses, or tenderness. X-rays revealed T2-T6 49 degree and T7-L1 31 degree curves. In addition, there was a T2-T6 65 degree kyphosis curve along with a collapsing T4 vertebra, C7 hemivertebra, and T5-T6 hemivertebrae.
    [Show full text]
  • Cleidocranial Dysplasia
    Cleidocranial dysplasia Description Cleidocranial dysplasia is a condition that primarily affects development of the bones and teeth. Signs and symptoms of cleidocranial dysplasia can vary widely in severity, even within the same family. Individuals with cleidocranial dysplasia usually have underdeveloped or absent collarbones, also called clavicles ("cleido-" in the condition name refers to these bones). As a result, their shoulders are narrow and sloping, can be brought unusually close together in front of the body, and in some cases can be made to meet in the middle of the body. Delayed maturation of the skull (cranium) is also characteristic of this condition, including delayed closing of the growth lines where the bones of the skull meet (sutures) and larger than normal spaces (fontanelles) between the skull bones that are noticeable as "soft spots" on the heads of infants. The fontanelles normally close in early childhood, but they may remain open throughout life in people with this disorder. Some individuals with cleidocranial dysplasia have extra pieces of bone called Wormian bones within the sutures. Affected individuals are often shorter than other members of their family at the same age. Many also have short, tapered fingers and broad thumbs; flat feet; knock knees; short shoulder blades (scapulae); and an abnormal curvature of the spine (scoliosis). Typical facial features include a wide, short skull (brachycephaly); a prominent forehead; wide-set eyes (hypertelorism); a flat nose; and a small upper jaw. Individuals with cleidocranial dysplasia often have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture, at a relatively early age.
    [Show full text]
  • Ontology-Based Diagnostic Decision Support in Radiology
    78 e-Health – For Continuity of Care C. Lovis et al. (Eds.) © 2014 European Federation for Medical Informatics and IOS Press. This article is published online with Open Access by IOS Press and distributed under the terms of the Creative Commons Attribution Non-Commercial License. doi:10.3233/978-1-61499-432-9-78 Ontology-based Diagnostic Decision Support in Radiology Charles E. KAHN, Jr. a,1 a Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA Abstract. The Radiology Gamuts Ontology (RGO) is a knowledge model of diseases, interventions, and imaging manifestations. RGO incorporates 16,822 terms with their synonyms and abbreviations and 55,393 relationships between terms. Subsumption defines the relationship between more general and more specific terms; causality relates disorders and their imaging manifestations. We explored the application of the RGO to build an interactive decision support system for radiological diagnosis. The Gamuts DDx system was created to apply the RGO's knowledge: it identifies a list of potential diagnoses in response to one or more user-specified imaging observations. The system also identifies a set of observations that allow one to narrow the diagnosis, and dynamically narrows or expands the list of diagnoses as imaging findings are selected or deselected. The functionality has been implemented as a web-based user interface and as a web service. The current work demonstrates the feasibility of exploiting the RGO's causal knowledge to provide interactive decision support for diagnosis of imaging findings. Ongoing efforts include the further development of the system's knowledge base and evaluation of the system in clinical use.
    [Show full text]
  • Genetic Diseases Related with Osteoporosis
    Chapter 2 Genetic Diseases Related with Osteoporosis Margarita Valdés-Flores, Leonora Casas-Avila and Valeria Ponce de León-Suárez Additional information is available at the end of the chapter http://dx.doi.org/10.5772/55546 1. Introduction Osteoporosis is a disease entity characterized by the progressive loss of bone mineral density (BMD) and the deterioration of bone microarchitecture, leading to the development of frac‐ tures. Its classification encompasses two large groups, primary and secondary osteoporosis [1]. Primary osteoporosis is the disease’s most common form and results from the progressive loss of bone mass related to aging and unassociated with other illness, a natural process in adult life; its etiology is considered multifactorial and polygenic. This form currently represents a growing worldwide health problem due in part, to the contemporary environmental condi‐ tions of modern civilization. Risk factors that are considered as “modifiable” also play an important role and include physical activity, dietary habits and eating disorders. Furthermore, there is another group of associated risk factors that are considered “non-modifiable”, including gender, age, race, a personal and/or family history of fractures that in turn, indirectly reflect the degree of genetic susceptibility to this disease [2-4]. Secondary osteoporosis encompasses a large heterogeneous group of primary conditions favoring osteoporosis development. Table 1 summarizes some of the disease entities associated to primary and secondary osteoporosis. 1.1. Genetic aspects of primary osteoporosis This form of osteoporosis results from the interaction of several environmental and genetic factors, leading to difficulties in its study. It is not easy to define the magnitude of the effect of genetic susceptibility since it is a trait determined by multiple genes whose products affect the bone phenotype; moreover, the environmental factors compromising bone mineral density are also difficult to analyze.
    [Show full text]
  • Ocular Manifestations of Inherited Diseases Maya Eibschitz-Tsimhoni
    10 Ocular Manifestations of Inherited Diseases Maya Eibschitz-Tsimhoni ecognizing an ocular abnormality may be the first step in Ridentifying an inherited condition or syndrome. Identifying an inherited condition may corroborate a presumptive diagno- sis, guide subsequent management, provide valuable prognostic information for the patient, and determine if genetic counseling is needed. Syndromes with prominent ocular findings are listed in Table 10-1, along with their alternative names. By no means is this a complete listing. Two-hundred and thirty-five of approxi- mately 1900 syndromes associated with ocular or periocular manifestations (both inherited and noninherited) identified in the medical literature were chosen for this chapter. These syn- dromes were selected on the basis of their frequency, the char- acteristic or unique systemic or ocular findings present, as well as their recognition within the medical literature. The boldfaced terms are discussed further in Table 10-2. Table 10-2 provides a brief overview of the common ocular and systemic findings for these syndromes. The table is organ- ized alphabetically; the boldface name of a syndrome is followed by a common alternative name when appropriate. Next, the Online Mendelian Inheritance in Man (OMIM™) index num- ber is listed. By accessing the OMIM™ website maintained by the National Center for Biotechnology Information at http://www.ncbi.nlm.nih.gov, the reader can supplement the material in the chapter with the latest research available on that syndrome. A MIM number without a prefix means that the mode of inheritance has not been proven. The prefix (*) in front of a MIM number means that the phenotype determined by the gene at a given locus is separate from those represented by other 526 chapter 10: ocular manifestations of inherited diseases 527 asterisked entries and that the mode of inheritance of the phe- notype has been proven.
    [Show full text]