DOCSLIB.ORG

Fetal Skeletal Lethal Dysplasia: Case Report Displasia Esquelética Letal Fetal: Relato De Caso

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Fetal Skeletal Lethal Dysplasia: Case Report Displasia Esquelética Letal Fetal: Relato De Caso THIEME 576 Case Report Fetal Skeletal Lethal Dysplasia: Case Report Displasia Esquelética Letal Fetal: Relato de Caso Alexandre Mello Savoldi1,2,3 Maria Auxiliadora Monteiro Villar1,2,3 Heloisa Novaes Machado2,4 Juan C. Llerena Júnior1,2,3,5,6 1 Center for Medical Genetics and Center for Rare Diseases, Instituto Address for correspondence Juan Clinton Llerena Jr., MD, PhD, Nacional Fernandes Figueira (IFF), Fundação Oswaldo Cruz (Fiocruz), Instituto Nacional Fernandes Figueira, IFF/Fiocruz, Av. Rui Barbosa, Rio de Janeiro, RJ, Brazil 716, 22.250-020 - Rio de Janeiro, RJ, Brasil 2 LatinAmericanCollaborativeStudy of Congenital Malformations (e-mail: llerena@iff.fiocruz.br). (ECLAMC), Hospital A05, Instituto Nacional Fernandes Figueira (IFF), Fiocruz, Rio de Janeiro, RJ, Brazil 3 Reference Center for Osteogenesis Imperfecta (CROI), Instituto Nacional Fernandes Figueira (IFF), Fiocruz, Rio de Janeiro, RJ, Brazil 4 Pathological Anatomy Service, Instituto Nacional Fernandes Figueira (IFF), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brasil 5 Instituto Nacional de Genética Médica Populacional (Inagemp), Rio de Janeiro, RJ, Brazil 6 Fundação Arthur Sá Erp, Faculdade de Medicina de Petrópolis, Rio de Janeiro, RJ, Brazil Rev Bras Ginecol Obstet 2017;39:576–582. Abstract The clinical management and decision-making in pregnancies in which there is Keywords suspicion of lethal fetal malformations during the prenatal period, such as lethal ► pregnancy skeletal dysplasia (SD), demand a multidisciplinary approach coordinated by an ► skeletal dysplasia experienced physician. Based on the presentation of a case of osteogenesis imperfecta ► osteogenesis type IIA, we offer and discuss recommendations with the intention of organizing imperfecta clinical and laboratory investigations aiming toward the clinical management, prog- ► prenatal period nosis, and etiological diagnosis of these malformations, as well as genetic counselling ► genetic syndromes topatientswhowishtobecomepregnant. Resumo O manejo clínico e a tomada de decisões médicas em gestantes com suspeita de Palavras-chave malformação letal em um feto no período pré-natal, tal qual uma displasia esquelética ► gravidez letal, demandam uma abordagem multidisciplinar coordenada por um médico experi- ► displasia esquelética ente. Baseado na apresentação de um caso de osteogênese imperfeita tipo IIA, ► osteogênese recomendações são apresentadas e discutidas com a intenção de organizar as imperfeita investigações clínicas e laboratoriais visando o manejo clínico, o prognóstico, e o ► período pré-natal diagnóstico etiológico dessas malformações, e o aconselhamento genético para as ► síndromes genéticas pacientes que desejam engravidar. Introduction heterogeneous characteristics. They affect the bone tissue and cartilage, resulting in changes in the growth, shape and Skeletal dysplasias (SDs), or osteochondrodysplasias (OCDs), development of the skeletal system. The OCDs can be very are a group of bone disorders with clinical and etiological rare; however, as a group, their prevalence is estimated at received DOI https://doi.org/ Copyright © 2017 by Thieme Revinter December 13, 2016 10.1055/s-0037-1603943. Publicações Ltda, Rio de Janeiro, Brazil accepted ISSN 0100-7203. April 4, 2017 published online August 7, 2017 FetalSkeletalLethalDysplasia:CaseReport Savoldi et al. 577 around 2.4 per 10,000 live births1,2, with the lethal SD forms physicians to define proper etiological diagnosis and clinical – corresponding to 0.95-1.5 per 10,000 births.1 3 It is known prognosis, as well as genetic counselling, once few of these that there are more than 456 entities classified into 40 genetic disorders may present with considerable recurrence categories by their cardinal features (radiological findings, risks. molecular etiology, inheritance), among which 40% can be This article aims, through the presentation of a clinical already detected in the perinatal period, representing 9 case of a lethal SD with radiological features (OI type IIA), to deaths per 1,000 births.1,4 review the most common lethal SDs in the perinatal period, Osteogenesis imperfecta type II (OI type II) comprises 14% highlight their clinical and radiologic features, and compare of lethal SDs, and is the second most common cause, among the reported case with the literature. Furthermore, recom- thanatophoric dysplasia (26%) and the achondrogenesis (9%) mendations for the clinical management of similar cases are – group, which represents 40–60% of all lethal SDs.1,5 7 Oste- discussed. ogenesis imperfecta type II is a genetic disorder of the connective tissue characterized by severe bone fragility, Clinical Case Description susceptibility to severe deformities, and the occurrence of several pathological fractures, with predominance of de novo A 33-year-old pregnant woman in her 6th pregnancy, with 5 autosomal dominant inheritance caused by mutations in previous vaginal deliveries, was referred to our outpatient genes COL1A1 and COL1A2.8 Multiple fractures are frequent prenatal clinic due to a malformation in her fetus detected by in utero, and perinatal death occurs in the majority of cases,9 an ultrasound in the Family Care Clinic. Her family history where most prenatal diagnosis are suspected primarily by was unremarkable. A prenatal ultrasound fetal biometry at early fetal ultrasound, and confirmed by skeletal radiogra- 23 weeks of pregnancy revealed an estimated fetal weight of phy, autopsy and, less frequently, by molecular tests. 505 g and shortening of the long bones, so the hypothesis of Due to the suspicion of a presumptive diagnosis of SD based an SD was considered. At 39 weeks of pregnancy, an ultra- on early gestational ultrasound findings, a range of clinical sound revealed an estimated fetal weight of 815 g and fetal diagnosis with different outcomes may be considered. Based malformations characterized by hypotelorism, short and on the severity of the condition, such considerations and saddled nose, micrognathia with redundancy of soft tissue observations can impose difficulties to an appropriate clinical in the face and neck, very short ribs, and narrow thoracic cage management of these fetuses, the pregnant women, and their (►Fig. 1a). Furthermore, it was possible to observe skeletal families regarding genetic counselling. abnormalities with shortening of the limbs more pro- In face of a medical emergency for the fetus with a nounced in the femora and humeri. Fetal hypocalcification presumed lethal SD, and the presence of a rather uniform of the skull was evident, and complete and normal visuali- gestational ultrasound phenotype among lethal SDs, clinical zation of the encephalon, cerebral hemispheres, ventricles management guidelines become crucial. They may assist and the posterior fossa was apparently present. A fetal Fig. 1 Obstetric ultrasound and fetal development quantile curves of OI type IIA – 38 weeks. Rev Bras Ginecol Obstet Vol. 39 No. 10/2017 578 FetalSkeletalLethalDysplasia:CaseReport Savoldi et al. echocardiography showed normal cardiac activity, with a humeri and femora, abnormally shaped ribs containing thoracic diameter well below the third percentile, in addition numerous fractures (“pearl appearance”), and a vertebral to the presence of a mild to moderate tricuspid regurgitation. column with flattened vertebrae (platyspondylia) (►Fig. 2). The small thoracic diameter suggested a high probability of Based on the clinical and radiological evidences, the severe pulmonary hypoplasia. patient was diagnosed as having OI type IIA (lethal form) A history of Zika virus infection was suspected when the (►Figs. 1, 2, 3). mother was 20 weeks and 4 days pregnant due to clinical manifestations described as arthralgia during 10 days, mod- Discussion erate fever, and erythematous exanthema spots on the body. Real-time polymerase chain reaction (PCR) for Zika virus The lethal forms of SD represent a group of genetic disorders could not be performed. that are clinically and genetically heterogeneous, and whose At 39 weeks and 3 days of gestational age, the patient cardinal manifestations are observed in the perinatal period delivered a singleton male live newborn with facial malforma- with severe and prominent phenotypic features. The major- tion and very short limbs. The Apgar score was 1 for the 1st ity of deaths result from respiratory insufficiency due to minute of life, and 0 for the 5th minute. The newborn died due to pulmonary hypoplasia, with 23% of stillbirths and 32% of cardiorespiratory arrest 15 minutes after birth. A post-mortem babies not surviving the first week of life.1,4 In a clinical examination of the baby was performed after we obtained the routine basis, the diagnosis of lethal SD occurs more fre- parents’ authorization, and it included skeletal X-ray scans. quently in the second trimester of gestation, through ultra- Genetic molecular tests were not performed (►Fig. 2). sound findings (85%) and changes related to bone mineral The anatomopathological study revealed a deformed ne- density, including pathological fractures, growth deficiency, onate boy measuring 38 cm (below the 3rd percentile) and rib abnormalities, bowing or shortening of the long bones, weighing 1,800 g (below the 3rd percentile), with extreme and abnormal skull ossification, can be observed.10 However, shortening of all members. The skull was very soft, with no the ultrasonography findings do not always point to a cranium ossification, and visualization of the meninges was specific SD, which may lead to an imprecise diagnosis, evident.
Load more

Recommended publications
  • 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.
    [Show full text]
  • Prestin, a Cochlear Motor Protein, Is Defective in Non-Syndromic Hearing Loss
    Human Molecular Genetics, 2003, Vol. 12, No. 10 1155–1162 DOI: 10.1093/hmg/ddg127 Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss Xue Zhong Liu1,*, Xiao Mei Ouyang1, Xia Juan Xia2, Jing Zheng3, Arti Pandya2, Fang Li1, Li Lin Du1, Katherine O. Welch4, Christine Petit5, Richard J.H. Smith6, Bradley T. Webb2, Denise Yan1, Kathleen S. Arnos4, David Corey7, Peter Dallos3, Walter E. Nance2 and Zheng Yi Chen8 1Department of Otolaryngology, University of Miami, Miami, FL 33101, USA, 2Department of Human Genetics, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0033, USA, 3Department of Communication Sciences and Disorders, Auditory Physiology Laboratory (The Hugh Knowles Center), Northwestern University, Evanston, IL, USA, 4Department of Biology, Gallaudet University, Washington, DC 20002, USA, 5Unite´ de Ge´ne´tique des De´ficits Sensoriels, CNRS URA 1968, Institut Pasteur, Paris, France, 6Department of Otolaryngology University of Iowa, Iowa City, IA 52242, USA, 7Neurobiology Department, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA, USA and 8Department of Neurology, Massachusetts General Hospital and Neurology Department, Harvard Medical School Boston, MA 02114, USA Received January 14, 2003; Revised and Accepted March 14, 2003 Prestin, a membrane protein that is highly and almost exclusively expressed in the outer hair cells (OHCs) of the cochlea, is a motor protein which senses membrane potential and drives rapid length changes in OHCs. Surprisingly, prestin is a member of a gene family, solute carrier (SLC) family 26, that encodes anion transporters and related proteins. Of nine known human genes in this family, three (SLC26A2, SLC26A3 and SLC26A4 ) are associated with different human hereditary diseases.
    [Show full text]
  • 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.
    [Show full text]
  • 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
    [Show full text]
  • 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]
  • Current Overview of Osteogenesis Imperfecta
    medicina Review Current Overview of Osteogenesis Imperfecta Mari Deguchi *, Shunichiro Tsuji , Daisuke Katsura , Kyoko Kasahara, Fuminori Kimura and Takashi Murakami Department of Obstetrics & Gynecology, Shiga University of Medical Science, Otsu 520-2192, Shiga, Japan; [email protected] (S.T.); [email protected] (D.K.); [email protected] (K.K.); [email protected] (F.K.); [email protected] (T.M.) * Correspondence: [email protected] Abstract: Osteogenesis imperfecta (OI), or brittle bone disease, is a heterogeneous disorder charac- terised by bone fragility, multiple fractures, bone deformity, and short stature. OI is a heterogeneous disorder primarily caused by mutations in the genes involved in the production of type 1 collagen. Severe OI is perinatally lethal, while mild OI can sometimes not be recognised until adulthood. Severe or lethal OI can usually be diagnosed using antenatal ultrasound and confirmed by various imaging modalities and genetic testing. The combination of imaging parameters obtained by ultrasound, computed tomography (CT), and magnetic resource imaging (MRI) can not only detect OI accurately but also predict lethality before birth. Moreover, genetic testing, either noninvasive or invasive, can further confirm the diagnosis prenatally. Early and precise diagnoses provide parents with more time to decide on reproductive options. The currently available postnatal treatments for OI are not curative, and individuals with severe OI suffer multiple fractures and bone deformities throughout their lives. In utero mesenchymal stem cell transplantation has been drawing attention as a promising therapy for severe OI, and a clinical trial to assess the safety and efficacy of cell therapy is currently ongoing.
    [Show full text]
  • Hypochondroplasia and Acanthosis Nigricans
    European Journal of Endocrinology (2008) 159 243–249 ISSN 0804-4643 CLINICAL STUDY Hypochondroplasia and acanthosis nigricans: a new syndrome due to the p.Lys650Thr mutation in the fibroblast growth factor receptor 3 gene? Lidia Castro-Feijo´o*, Lourdes Loidi1,*, Anxo Vidal2, Silvia Parajes1, Elena Roso´n3,AnaA´ lvarez4, Paloma Cabanas, Jesu´s Barreiro, Adela Alonso4, Fernando Domı´nguez1,2 and Manuel Pombo Unidad de Endocrinologı´a Pedia´trica, Crecimiento y Adolescencia, Departamento de Pediatrı´a, Hospital Clı´nico Universitario y Universidad de Santiago de Compostela, 15706 Santiago de Compostela, Spain, 1Unidad de Medicina Molecular, Fundacio´nPu´blica Galega de Medicina Xeno´mica, 15706 Santiago de Compostela, Spain, 2Departamento de Fisiologı´a, Universidad de Santiago de Compostela, 15702 Santiago de Compostella, Spain, 3Servicio de Dermatologı´a, Complejo Hospitalario de Pontevedra, 36001 Pontevedra, Spain and 4Servicio de Radiologı´a, Hospital Clı´nico Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain (Correspondence should be addressed to M Pombo; Email: [email protected]) *L Castro-Feijo´o and L Loidi contributed equally to this work Abstract Background: Hypochondroplasia (HCH) is a skeletal dysplasia inherited in an autosomal dominant manner due, in most cases, to mutations in the fibroblast growth factor receptor 3 (FGFR3). Acanthosis nigricans (AN) is a velvety and papillomatous pigmented hyperkeratosis of the skin, which has been recognized in some genetic disorders more severe than HCH involving the FGFR3 gene. Objective and design: After initial study of the proband, who had been consulted for short stature and who also presented AN, the study was extended to the patient’s mother and to 12 additional family members.
    [Show full text]
  • Infant with Thanatophoric Dysplasia: a Clue to the Locus of the Candidate Gene 295
    JMed Genet 1995;32:293-295 293 De novo 1;1O balanced translocation in an infant with thanatophoric dysplasia: a clue to the locus of the candidate gene J Med Genet: first published as 10.1136/jmg.32.4.293 on 1 April 1995. Downloaded from J H Hersh, FF Yen, S C Peiper, M J Barch, 0 A Yacoub, D H Voss, J L Roberts Abstract Histopathologically, the growth plate in TD is A female infant with thanatophoric dys- interrupted by tufts of ossifying tissue, ex- plasia was found to have a de novo trans- hibiting features of both endochondral and location involving chromosomes 1 and 10. membranous ossification.5 The chromosome abnormality may rep- TD is thought to be transmitted in an auto- resent an important clue in identifying the somal dominant fashion.5 Since most cases of locus for the candidate gene responsible TD are sporadic, its occurrence in an infant is for this lethal skeletal dysplasia. presumed to be the result of a new autosomal dominant mutation.6 We report the first case (JMed Genet 1995;32:293-295) of TD in which an apparent de novo balanced reciprocal translocation was present in the affected infant. Thanatophoric dysplasia (TD) is the most com- mon lethal skeletal dysplasia with a livebirth prevalence estimated to be between 0-28 and Case report 0 6/10000.2 Clinically affected infants have A white female, who was the second of twins, marked limb shortening and a small thorax, was born at 36 weeks' gestation to a 29 year and death usually occurs in the neonatal period old G2P1 woman and her 36 year old husband.
    [Show full text]
  • Ultrasonic Demonstration of Fetal Skeletal Dysplasia Case Reports
    222 SAMJ VOLUME 67 9 FEBRUARY 1985 Ultrasonic demonstration of fetal skeletal dysplasia Case reports L1NNIE M. MULLER, B. J. CREMIN Toshiba linear array scanners (with 3,5 mHz transducers) and a Philips SDU 7000 Sector/Static scanner. A routine obstetric Summary scan does not involve complete examination of all limbs, but Reports on prenatal diagnosis in cases of skeletal when a bony abnormality is noted a skeletal survey is dysplasia have mostly been in high-risk mothers attempted. Real-time ultrasound offers a flexible technique, with a suspect genetic background where the fetal and when the infant is in the prone vertex position the linear lesion could probably be predetermined. We deal array has the advantage of a wider range of skeletal visualiza­ with routine ultrasonographic appraisal of the fetal tion. skeleton when dysplasia is not initially suspected, A complete skeletal survey consists of an evaluation of the and relate our experience of the lethal forms of this bones of the skull, spine, thorax and limbs and of correlating these other fetal structures. We first measured the biparietal condition. During the 4-year period 1981 - 1984,6 cases of skeletal dysplasia, including thanatophoric diameter (BPD) and then noted the echogenic characteristics dysplasia, achondrogenesis, the Ellis-van Creveld of the skull and facial contours. A comprehensive evaluation of syndrome (chondro-ectodermal dysplasia) and the spine is possible from 17 weeks' gestation onwards. In a osteogenesis imperfecta, were detected; the ultra­ longitudinal plane the posterior elements form segmented sonographic findings are discussed. bands of echoes that conform to the fetal kyphosis, but it is not always possible to visualize the whole spine.
    [Show full text]
  • Prevalence and Incidence of Rare Diseases: Bibliographic Data
    Number 1 | January 2019 Prevalence and incidence of rare diseases: Bibliographic data Prevalence, incidence or number of published cases listed by diseases (in alphabetical order) www.orpha.net www.orphadata.org If a range of national data is available, the average is Methodology calculated to estimate the worldwide or European prevalence or incidence. When a range of data sources is available, the most Orphanet carries out a systematic survey of literature in recent data source that meets a certain number of quality order to estimate the prevalence and incidence of rare criteria is favoured (registries, meta-analyses, diseases. This study aims to collect new data regarding population-based studies, large cohorts studies). point prevalence, birth prevalence and incidence, and to update already published data according to new For congenital diseases, the prevalence is estimated, so scientific studies or other available data. that: Prevalence = birth prevalence x (patient life This data is presented in the following reports published expectancy/general population life expectancy). biannually: When only incidence data is documented, the prevalence is estimated when possible, so that : • Prevalence, incidence or number of published cases listed by diseases (in alphabetical order); Prevalence = incidence x disease mean duration. • Diseases listed by decreasing prevalence, incidence When neither prevalence nor incidence data is available, or number of published cases; which is the case for very rare diseases, the number of cases or families documented in the medical literature is Data collection provided. A number of different sources are used : Limitations of the study • Registries (RARECARE, EUROCAT, etc) ; The prevalence and incidence data presented in this report are only estimations and cannot be considered to • National/international health institutes and agencies be absolutely correct.
    [Show full text]
  • WES Gene Package Multiple Congenital Anomalie.Xlsx
    Whole Exome Sequencing Gene package Multiple congenital anomalie, version 5, 1‐2‐2018 Technical information DNA was enriched using Agilent SureSelect Clinical Research Exome V2 capture and paired‐end sequenced on the Illumina platform (outsourced). The aim is to obtain 8.1 Giga base pairs per exome with a mapped fraction of 0.99. The average coverage of the exome is ~50x. Duplicate reads are excluded. Data are demultiplexed with bcl2fastq Conversion Software from Illumina. Reads are mapped to the genome using the BWA‐MEM algorithm (reference: http://bio‐bwa.sourceforge.net/). Variant detection is performed by the Genome Analysis Toolkit HaplotypeCaller (reference: http://www.broadinstitute.org/gatk/). The detected variants are filtered and annotated with Cartagenia software and classified with Alamut Visual. It is not excluded that pathogenic mutations are being missed using this technology. At this moment, there is not enough information about the sensitivity of this technique with respect to the detection of deletions and duplications of more than 5 nucleotides and of somatic mosaic mutations (all types of sequence changes). HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered % covered gene symbol gene ID >10x >20x >30x A4GALT [Blood group, P1Pk system, P(2) phenotype], 111400 607922 101 100 100 99 [Blood group, P1Pk system, p phenotype], 111400 NOR polyagglutination syndrome, 111400 AAAS Achalasia‐addisonianism‐alacrimia syndrome, 231550 605378 73 100 100 100 AAGAB Keratoderma, palmoplantar,
    [Show full text]
  • Blueprint Genetics Craniosynostosis Panel
    Craniosynostosis Panel Test code: MA2901 Is a 38 gene panel that includes assessment of non-coding variants. Is ideal for patients with craniosynostosis. About Craniosynostosis Craniosynostosis is defined as the premature fusion of one or more cranial sutures leading to secondary distortion of skull shape. It may result from a primary defect of ossification (primary craniosynostosis) or, more commonly, from a failure of brain growth (secondary craniosynostosis). Premature closure of the sutures (fibrous joints) causes the pressure inside of the head to increase and the skull or facial bones to change from a normal, symmetrical appearance resulting in skull deformities with a variable presentation. Craniosynostosis may occur in an isolated setting or as part of a syndrome with a variety of inheritance patterns and reccurrence risks. Craniosynostosis occurs in 1/2,200 live births. Availability 4 weeks Gene Set Description Genes in the Craniosynostosis Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ALPL Odontohypophosphatasia, Hypophosphatasia perinatal lethal, AD/AR 78 291 infantile, juvenile and adult forms ALX3 Frontonasal dysplasia type 1 AR 8 8 ALX4 Frontonasal dysplasia type 2, Parietal foramina AD/AR 15 24 BMP4 Microphthalmia, syndromic, Orofacial cleft AD 8 39 CDC45 Meier-Gorlin syndrome 7 AR 10 19 EDNRB Hirschsprung disease, ABCD syndrome, Waardenburg syndrome AD/AR 12 66 EFNB1 Craniofrontonasal dysplasia XL 28 116 ERF Craniosynostosis 4 AD 17 16 ESCO2 SC phocomelia syndrome, Roberts syndrome
    [Show full text]