S2 Table. Genetic Syndromes Displaying Various Craniofacial Abnormalities, Used to Locate Candidate Genes for the Study

Total Page:16

File Type:pdf, Size:1020Kb

S2 Table. Genetic Syndromes Displaying Various Craniofacial Abnormalities, Used to Locate Candidate Genes for the Study S2 Table. Genetic syndromes displaying various craniofacial abnormalities, used to locate candidate genes for the study. Syndrome Symptoms Prevalence Genetic origin Aarskog syndrome Distinct facial features, such as: rounded face, Rare Mutations in FGDY1 (OMIM:100050) underdeveloped mid-portion of the face (maxilla), gene on X chromosome small nose with nostrils tipped forward [1] (anteverted), wide-set eyes, crease below the lower lip (hypertelorism) Alagille syndrome Distinct facial features, such as broad forehead, 1 in 70,000 Mutations in JAG1 gene (OMIM: 118450) pointed mandible and bulbous tip of the nose and [2] in the fingers Alfi's Syndrome Mental retardation, trigonocephaly, mongoloid 1 in 5 million Monosomy 9p or (OMIM: 158170) eyes, wide flat nasal bridge, anteverted nostrils, 9p22.2-3 deletion [3] long upper lip, cleft lip/palate, short neck, long digits mostly secondary to long middle phalanges Apert Syndrome Various manifestations of craniosynostosis with Between 1 in Mutations in FGFR2 (OMIM: 101200) cleft lip/palate. 65,000 to gene [4] 200,000 Beckwith- Characteristic facial appearance and indentations Rare Mutation or deletion of Wiedemann of the ears, a large tongue which may cause genes H19, KCNQ1OT1 Syndrome breathing, feeding or speech difficulties, one side or CDKN1C in 11p15.5 (OMIM: 130650) of the body grows more than the other chromosomal region [5- 7] Cohen Syndrome Abnormalities of the head, characteristic facial Rare Mutations in COH1 (OMIM: 216550) features including high-arched or wave-shaped gene [8] eyelids, a short philtrum, thick hair, and low hairline Cri-du-chat Abnormal larynx and epiglottis which causes a 1 in 50,000 Mutations in two Syndrome (OMIM: distinct sounding cry. The name literally means live births candidate genes: 123450). Other “cry of the cat.” Other symptoms include mental Semaphorine F name: 5p deletion retardation, small head (microcephaly). (SEMA5A) and delta syndrome Characteristic facial features at birth include a catenin (CTNND2), large nasal bridge, round face, wide-spaced eyes, potentially involved in low-set ears, and a down-turned mouth. As the cerebral development child gets older the facial features change and a [9] long, narrow face is more commonly observed Crouzon Syndrome Craniosynostosis disorder causing secondary 1 in 60,000 Mutations in FGFR2 (OMIM: 123500) alterations of the facial bones and facial structure. gene [10,11] Common features include hypertelorism, parrot- beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism Down Syndrome People with Down Syndrome have similar facial 1 in 600-1000 Extra copy of (OMIM: 190685). features including a flattened facial profile, live births. chromosome 21 in each Other name: upward slanting eyes, small over-folded ears, flat Trisomy 21 is cell. Each person with Trisomy 21 nose and small mouth with a protruding tongue. the most Down syndrome may They can also have low muscle tone, a shorter common have slightly different than typical neck, a single crease across the palm trisomy seen symptoms due to of the hand, heart defects, and varying levels of in live born variations in intellectual disability individuals chromosomal abnormalities (e.g. Partial or full copy of chromosome 21). Several candidate genes have been identified in Down syndrome critical region, such as DSCR1, DSCR2, DSCR3 and DSCR4 [12] and SHH [13] Edward Syndrome. Small head (microcephaly), small jaw/mouth 1 in 3000- Extra chromosome 18 in Other name: (micrognathia), low-set malformed ears, cleft 8000 live each cell. Trisomy 18 is Trisomy 18 lip/cleft palate, upturned nose, narrow eyelid births. 80% of the second most folds, widely spaced eyes, clenched fists with people with common trisomy seen in overlapping fingers, mental retardation, growth this condition live born individuals deficiency and other skeletal and organ anomalies are female Floating-Harbor Short stature, a triangular shaped face with broad Rare Mutations in SRCAP Syndrome (OMIM: bulbous nose, long eyelashes, deep-set eyes and a located in 16p11.2 136140) wide mouth with thin lips chromosomal region [14]. Rubinstein-Taybi syndrome (OMIM: 180849) shows phenotypic overlap with Floating-Harbor syndrome and is caused by mutation in the CREBBP gene, for which SRCAP is a coactivator Fragile X Range of learning disorders, distinctive facial A mutation in the FMR1 Syndrome appearance with large ears and a long face, gene located on the X (OMIM:300624) prominent jaws, speech and language problems chromosome [15,16]. Within this gene, there is a region containing the sequence “CGG”, which is repeated multiple times. Normally the sequence is repeated no more than 55 times in the gene. However, Fragile X Syndrome occurs when a person has more than 200 “CGG” repeats in the FMR1 gene. A person who has more than 55 repeats, but less than 200, is considered a “pre-mutation carrier.” These individuals do not have Fragile X Syndrome themselves but are at risk of having children affected with the disorder since the number of repeats could expand in the next generation Langer-Giedion Short stature, small head, distinctive facial Rare Deletion of 8q23.2 to Syndrome features including deep-set eyes, a bulbous nose, q24.1 chromosomal (OMIM:190350 ) long narrow upper lip and missing teeth region. Candidate gene in this region: EXT1[17] Noonan Syndrome Variable phenotype, which may change with age, 1 in 1,000 to Mutation in the PTPN11 (OMIM:163950) many characteristics of which overlap those of the 2,500 live gene on chromosome Turner syndrome. Short stature and mild mental births 12q24.1[18,19] retardation are the main features of this syndrome. Characteristic facial features including short webbed neck and low-set posteriorly rotated ears Pallister Killian Coarse face with a high forehead, sparse hair on Rare Mosaicism for Syndrome (OMIM: the scalp, an abnormally wide space between the tetrasomy of 601803) eyes, a fold of the skin over the inner corner of the chromosome 12p [20] eyes and a flat nasal bridge with a highly arched palate Patau Syndrome Common features include: heart defects, small 1 in 10,000 Trisomy of chromosome Other name: heads (microcephaly), cleft lip and/or palate, 13 [21] Trisomy 13 small eyes that are close together, extra fingers (polydactyly) and various skeletal abnormalities Pfeiffer Syndrome Craniosynostosis, midface deficiency, cloverleaf 1 in 100,000 Mutations in FGFR1, (OMIM: 101600). skull, broad thumbs, broad great toes FGFR2 and FGFR3 Other name: [22,23] Craniofacial- Skeletal- Dermatologic Dysplasia type 1, 2 and 3. Saethre-Chotzen Acrocephaly, asymmetry of the skull, low set 1 in 25,000 to Mutations in FGFR2 Syndrome hairline, wide and tall forehead, thin, long pointed 50,000 and TWIST1 [24-27] (OMIM:101400). nose, small low-set ears, cleft palate Other name: Acrocephalosyndac tyly type III Smith-Magenis Abnormalities of the craniofacial area such as Rare Mutations in RAI1 gene Syndrome (OMIM: brachycephaly, midface hypoplasia, small ears, [28,29] 182290) broad nose and cleft palate. Overlapping features with Potocki-Lupski syndrome Treacher Collins Various craniofacial abnormalities such as 1 in 25,000 to Mutations in TCOF1 Syndrome antimongoloid slant of the eyes, coloboma of the 50,000 gene [30-33] (OMIM:154500) lid, micrognathia, microtia and other deformity of the ears, hypoplastic zygomatic arches and macrostomia Turner Syndrome People with Turner Syndrome are females and 1 out of 2,500 Females with only one (Monosomy X) typically have short stature, a webbed neck, heart girls X chromosome [34]. defects, swelling of the hands and feet, and Potential involvement of characteristic facial features SHOX gene [35] Velo-Cardio-Facial Highly variable phenotype with cleft palate, heart 1 out of 4000 Point mutations in Syndrome (OMIM: abnormalities, typical faces and over 180 other live births TBX1 [36-38] 192430) clinical findings Waardenburg Characterized by pigmentary abnormalities of the Rare Mutations in PAX3 gene Syndrome (OMIM: hair, skin, eyes and facial structures, including [39]. 193500) broad nasal bridge References 1. Orrico A, Galli L, Cavaliere ML, Garavelli L, Fryns J-P, et al. (2003) Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients. Eur J Hum Genet 12: 16-23. 2. Kamath BM, Stolle C, Bason L, Colliton RP, Piccoli DA, et al. (2002) Craniosynostosis in Alagille syndrome. Am J Med Genet 112: 176-180. 3. Kawara H, Yamamoto T, Harada N, Yoshiura K, Niikawa N, et al. (2006) Narrowing candidate region for monosomy 9p syndrome to a 4.7-Mb segment at 9p22.2-p23. Am J Med Genet A 140: 373-377. 4. Andreou A, Lamy A, Layet V, Cailliez D, Gobet F, et al. (2006) Early-onset low-grade papillary carcinoma of the bladder associated with Apert syndrome and a germline FGFR2 mutation (Pro253Arg). Am J Med Genet A 140: 2245-2247. 5. Hatada I, Ohashi H, Fukushima Y, Kaneko Y, Inoue M, et al. (1996) An imprinted gene p57KIP2 is mutated in Beckwith–Wiedemann syndrome. Nat Gen 14: 171-173. 6. Catchpoole D, Smallwood AV, Joyce JA, Murrell A, Lam W, et al. (2000) Mutation analysis of H19 and NAP1L4 (hNAP2) candidate genes and IGF2 DMR2 in Beckwith-Wiedemann syndrome. J Med Genet 37: 212-215. 7. Weksberg R, Shuman C, Caluseriu O, Smith AC, Fei YL, et al. (2002) Discordant KCNQ1OT1 imprinting in sets of monozygotic twins discordant for Beckwith-Wiedemann syndrome. Hum Mol Genet 11: 1317-1325. 8. Kolehmainen J, Wilkinson R, Lehesjoki AE, Chandler K, Kivitie-Kallio S, et al. (2004) Delineation of Cohen syndrome following a large-scale genotype-phenotype screen. Am J Hum Genet 75: 122-127. 9. Wu Q, Niebuhr E, Yang H, Hansen L (2005) Determination of the 'critical region' for cat-like cry of Cri-du-chat syndrome and analysis of candidate genes by quantitative PCR.
Recommended publications
  • Basic Concepts in Basic Concepts in Dysmorphology
    Basic Concepts in Dysmorphology Samia Temtamy* & Mona Aglan** *Professor of Human Genetics **Professor of Clinical Genetics Human Genetics & Genome Research Division National Research Centre, Cairo, Egypt OtliOutline y Definition of dysmorphology y Definition of terms routinely used in the description of birth defects y Impact of malformations y The difference between major & minor anomalies y Approach to a dysmorphic individual: y Suspicion & analysis y Systematic physical examination y CfitifdiConfirmation of diagnos is y Intervention y Summary 2 DfiitiDefinition of fd dysmorph hlology y The term “dysmorphology” was first coined by Dr. DidSithUSAiDavid Smith, USA in 1960s. y It implies study of human congenital defects and abnormalities of body structure that originate before birth. y The term “dysmorphic” is used to describe individuals whose physical fffeatures are not usually found in other individuals with the same age or ethnic background. y “Dys” (Greek)=disordered or abnormal and “Morph”=shape 3 Definition of terms routinely used in the d escri pti on of bi rth d ef ect s y A malformation / anomaly: is a primary defect where there i s a bas ic a ltera tion o f s truc ture, usuall y occurring before 10 weeks of gestation. y Examples: cleft palate, anencephaly, agenesis of limb or part of a limb. 4 Cleft lip & palate Absence of digits (ectrodactyly) y Malformation Sequence: A pattern of multiple defects resulting from a single primary malformation. y For example: talipes and hydrocephalus can result from a lumbar neural tube defect. Lumbar myelomeningeocele 5 y Malformation Syndrome: A pattern of features, often with an underlying cause, that arises from several different errors in morphogenesis.
    [Show full text]
  • 59. Lateral Facial Clefts
    59 LATERAL FACIAL CLEFTS LI OR TRANSVERSE CLEFTS ARE CONSIDERED THE RESULT OF FAILURE OF MESODERM MIGRATION OR MERGING TO OBLITERATE MANDIBULAR THE EMBRYONIC GROOVES BETWEEN THE MAXILLARY AND PROMINENCES TRANSVERSE CLEFTS AS THESE CLEFTS ARE RARE AND ALMOST EVERYBODY HAVING ONE HAS AND REPORTED IT IT IS POSSIBLE TO REVIEW MOST OF THE REPORTED CASES 769 DESCRIBED THE AFTER WHEN NOTE TREATMENT SPECIFIC CASE RECORDINGS IN WHAT MAY SEEM HELTERSKELTER ARRANGEMENT GENERALIZATIONS MAY BE OF VALUE IN 1891 ROSE NOTED FOR LONG THE VERY EXISTENCE OF THIS MACROSROMATOUS DEFORMITY WAS DOUBTED BUT CASES HAVE BEEN RECOGNIZED MORE OR LESS SINCE 1715 WHEN MURALT PICTURED IT FOR THE FIRST TIME ONE OF THE FIRST CASES REPORTED WAS BY VROLIK WHOIN HIS 1849 CLEFTS WORK GAVE SEVERAL ILLUSTRATIONS OF COMMISSURAL AS WELL AS OTHER DEFORMITIES OF THE FACE OTHER CASES WERE REPORTED BY REISSMANN IN 1869 AND MORGAN IN 1882 MACROSTOMIA OR COMMISSURAL HARELIP ACCORDING TO ROSE IS DIAMETER OF WHICH EVIDENCED BY AN INCREASED THE MOUTH MAY VARY IN FROM SLIGHT INCREASE TO CONSIDERABLE DISTANCE CASE RE PORTED BY RYND IN 1862 THE MOUTH OPENING EXTENDED AS FAR AS THE THE LEFT FIRST MOLAR ON THE RIGHT SIDE AND TO THE LAST MOLAR ON IN 1887 SUTTON PUBLISHED THE DRAWING OF CHILD WITH VERY LARGE RED CICATRIX THIS CLEFT THE ANGLES OF WHICH GRADUALLY PASSED INTO SCAR ENDED IN GAPING WOUND OVER THE TEMPORAL REGION EXTEND ING TO THE DURA MATER ROSE ALSO POINTED OUT MACROSROMA IS NOR ONLY ATTENDED BY GREAT DISFIGUREMENT HUT IS ALSO TROU BLESOME FROM THE IMPOSSIBILITY OF THE CHILD RETAINING
    [Show full text]
  • OCSHCN-10G, Medical Eligibility List for Clinical and Case Management Services.Pdf
    OCSHCN-10g (01 2019) (Rev 7-15-2017) Office for Children with Special Health Care Needs Medical Eligibility List for Clinical and Case Management Services BODY SYSTEM ELIGIBLE DISEASES/CONDITIONS ICD-10-CM CODES AFFECTED AUTISM SPECTRUM Autistic disorder, current or active state F84.0 Autistic disorder DISORDER (ASD) F84.3 Other childhood disintegrative disorder Autistic disorder, residual state F84.5 Asperger’s Syndrome F84.8 Other pervasive developmental disorder Other specified pervasive developmental disorders, current or active state Other specified pervasive developmental disorders, residual state Unspecified pervasive development disorder, current or active Unspecified pervasive development disorder, residual state CARDIOVASCULAR Cardiac Dysrhythmias I47.0 Ventricular/Arrhythmia SYSTEM I47.1 Supraventricular/Tachycardia I47.2 Ventricular/Tachycardia I47.9 Paroxysmal/Tachycardia I48.0 Paroxysmal atrial fibrillation I48.1 Persistent atrial fibrillationar I48.2 Chronic atrial fibrillation I48.3 Typical atrial flutter I48.4 Atypical atrial flutter I49.0 Ventricular fibrillation and flutter I49.1 Atrial premature depolarization I49.2 Junctional premature depolarization I49.3 Ventricular premature depolarization I49.49 Ectopic beats Extrasystoles Extrasystolic arrhythmias Premature contractions Page 1 of 28 OCSHCN-10g (01 2019) (Rev 7-15-2017) Office for Children with Special Health Care Needs Medical Eligibility List for Clinical and Case Management Services I49.5 Tachycardia-Bradycardia Syndrome CARDIOVASCULAR Chronic pericarditis
    [Show full text]
  • Dysmorphology Dysmorphism
    Dysmorphology Carolyn Jones, M.D., PhD Dysmorphism Morphologic developmental abnormalities. This may been seen in many syndromes of genetic or environmental origin. 1 Malformation A recognized dysmorphic feature. A structure not formed correctly. This can either be the cause of genetic factors or environment. 2 Deformation An external force resulting in the inability of a structure to form correctly. Example: club feet in a woman with oligohydramnios, fibroid tumors or multiple gestation. Disruption Birth defect resulting from the destruction of a normally forming structure. This can be caused by vascular occlusion, teratogen, or rupture of amniotic sac (amniotic band syndrome). 3 Common Dysmorphic features Wide spacing between eyes, hypertelorism Narrow spacing between eyes, hypotelorism Palpebral fissure length Epicanthal folds Common Dysmorphic Features Philtrum length Upper lip Shape of nose 4 Syndrome A number of malformations seen together Cause of Syndromes Chromosomal aneuploidy Single Gene abnormalities Teratogen exposure Environmental 5 Chromosomal Aneuploidy Nondisjuction resulting in the addition or loss of an entire chromosome Deletion of a part of a chromosome Microdeletion syndromes (small piece missing which is usually only detected using special techniques) 6 Common Chromosomal Syndromes caused by Nondisjuction Down syndrome (trisomy 21) Patau syndrome (trisomy 13) Edwards syndrome (trisomy 18) Turner syndrome (monosomy X) Klinefelter syndrome (47,XXY) Clinical Features at birth of Down syndrome Low set small ears Hypotonia Simian crease Wide space between first and second toe Flat face 7 Clinical Features of Down Syndrome Small stature Congenital heart defects (50-70%) Acquired and congenital hearing impairment. Duodenal atresia Hirshprungs disease Trisomy 13 Occurs in 1/5000 live births.
    [Show full text]
  • 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.
    [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]
  • Abstracts from the 50Th European Society of Human Genetics Conference: Electronic Posters
    European Journal of Human Genetics (2019) 26:820–1023 https://doi.org/10.1038/s41431-018-0248-6 ABSTRACT Abstracts from the 50th European Society of Human Genetics Conference: Electronic Posters Copenhagen, Denmark, May 27–30, 2017 Published online: 1 October 2018 © European Society of Human Genetics 2018 The ESHG 2017 marks the 50th Anniversary of the first ESHG Conference which took place in Copenhagen in 1967. Additional information about the event may be found on the conference website: https://2017.eshg.org/ Sponsorship: Publication of this supplement is sponsored by the European Society of Human Genetics. All authors were asked to address any potential bias in their abstract and to declare any competing financial interests. These disclosures are listed at the end of each abstract. Contributions of up to EUR 10 000 (ten thousand euros, or equivalent value in kind) per year per company are considered "modest". Contributions above EUR 10 000 per year are considered "significant". 1234567890();,: 1234567890();,: E-P01 Reproductive Genetics/Prenatal and fetal echocardiography. The molecular karyotyping Genetics revealed a gain in 8p11.22-p23.1 region with a size of 27.2 Mb containing 122 OMIM gene and a loss in 8p23.1- E-P01.02 p23.3 region with a size of 6.8 Mb containing 15 OMIM Prenatal diagnosis in a case of 8p inverted gene. The findings were correlated with 8p inverted dupli- duplication deletion syndrome cation deletion syndrome. Conclusion: Our study empha- sizes the importance of using additional molecular O¨. Kırbıyık, K. M. Erdog˘an, O¨.O¨zer Kaya, B. O¨zyılmaz, cytogenetic methods in clinical follow-up of complex Y.
    [Show full text]
  • Medical Genetics and Genomic Medicine in the United States of America
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by George Washington University: Health Sciences Research Commons (HSRC) Himmelfarb Health Sciences Library, The George Washington University Health Sciences Research Commons Pediatrics Faculty Publications Pediatrics 7-1-2017 Medical genetics and genomic medicine in the United States of America. Part 1: history, demographics, legislation, and burden of disease. Carlos R Ferreira George Washington University Debra S Regier George Washington University Donald W Hadley P Suzanne Hart Maximilian Muenke Follow this and additional works at: https://hsrc.himmelfarb.gwu.edu/smhs_peds_facpubs Part of the Genetics and Genomics Commons APA Citation Ferreira, C., Regier, D., Hadley, D., Hart, P., & Muenke, M. (2017). Medical genetics and genomic medicine in the United States of America. Part 1: history, demographics, legislation, and burden of disease.. Molecular Genetics and Genomic Medicine, 5 (4). http://dx.doi.org/10.1002/mgg3.318 This Journal Article is brought to you for free and open access by the Pediatrics at Health Sciences Research Commons. It has been accepted for inclusion in Pediatrics Faculty Publications by an authorized administrator of Health Sciences Research Commons. For more information, please contact [email protected]. GENETICS AND GENOMIC MEDICINE AROUND THE WORLD Medical genetics and genomic medicine in the United States of America. Part 1: history, demographics, legislation, and burden of disease Carlos R. Ferreira1,2 , Debra S. Regier2, Donald W. Hadley1, P. Suzanne Hart1 & Maximilian Muenke1 1National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 2Rare Disease Institute, Children’s National Health System, Washington, District of Columbia Correspondence Carlos R.
    [Show full text]
  • Goldenhar Syndrome
    ndrom Sy es tic & e G n e e n G e f Saxena and David, J Genet Syndr Gene Ther 2012, 3:2 T o Journal of Genetic Syndromes h l e a r n a DOI: 10.4172/2157-7412.1000113 r p u y o J & Gene Therapy ISSN: 2157-7412 Case Report Open Access Goldenhar Syndrome - A Rare Case Report Runjhun Saxena1* and Maria Priscilla David2 1Department of Oral Medicine and Radiology, Karnavati School of Dentistry, Uvarsad, Gandhinagar, Gujarat 382422, India 2Department of Oral Medicine and Radiology, M R Ambedkar Dental College,1/36 Cline Road, Cooke Town, Bangalore-05, India Abstract Goldenhar syndrome or oculo-auriculovertebral (OAV) is a rare abnormality affecting the craniofacial region having extracranial manifestations as well. First described by Maurice Goldenhar, its etiology still remains uncertain. We describes a case of Goldenhar syndrome with craniofacial manifestations which makes it amenable to diagnosis by an oral physician. Keywords: Goldenhar syndrome; Mandibular hypoplasia; • Hands / Fingers: clubbing, polydactyly, clinodactyly, single Periauricular tags; Corneal opacities palmar crease Introduction • Vertebral column anomalies (atlas occipitalization, synosto- sis, hemivertebrae, fused vertebrae, scoliosis, and bifid spine) Franceschetti-Goldenhar syndrome or Goldenhar syndrome, also [4]. known as facioauriculovertebral spectrum (FAV), first and second branchial arch syndrome, or oculo-auriculovertebral (OAV) spectrum Principal deformities of the Goldenhar syndrome are often is a rare congenital malformation which encompasses various combined with various malformations, such as: morphological and functional abnormalities. The syndrome was first • Cleft lip and/or palate, tongue cleft, unilateral tongue recorded by German physician Carl Ferdinand Von Arlt in 1845, hypoplasia, and parotid gland aplasia.
    [Show full text]
  • Patients with Noonan Syndrome Phenotype: Spectrum of Clinical Features and Congenital Heart Defect S
    Article PATIENTS WITH NOONAN SYNDROME PHENOTYPE: SPECTRUM OF CLINICAL FEATURES AND CONGENITAL HEART DEFECT S. Nshuti1,*, C. Hategekimana1,*, A. Uwineza2,, J. Hitayezu2, J. Mucumbitsi4, E. K. Rusingiza5, L. Mutesa2,# *These authors contributed equally to this work 1 Faculty of Medicine, National University of Rwanda, Butare, Rwanda; 2 Center for Medical Genetics, Faculty of Medicine, National University of Rwanda, Butare, Rwanda; Center for Human Genetics, CHU Sart Tilman, University of Liège, Belgium; 4 Department of Pediatrics, King Faysal Hospital, Kigali, Rwanda; 5 Department of Pediatrics, Kigali University Teaching Hospital, National University of Rwanda, Kigali, Rwanda; ABSTRACT Mutations in components of the RAS-MAPK signaling pathway have been reported to result in an expression of Noonan phenotype. This is actually a wide-spectrum-phenotype shared by Noonan syndrome and its clinically related disorders namely, the Cranio-facio-cutaneous (CFC) syndrome, Costillo syndrome as well as LEOPARD syndrome. Patients with Noonan Syndrome (NS) have mutations in PTPN11 gene in majority of cases. Recently, mutations in SOS1, RAF1, MEK1 and KRAS genes have been reported to cause NS as well. Objective: To report patients with a Noonan phenotype followed in Rwandan University Teaching Hospitals, and to show the importance of the clinical diagnosis and challenges of making the diagnosis in resource limited settings where karyotype is almost the only genetic investigation accessible. Patients and Methods: Here we are reporting 5 patients, all with relevant NS symptoms, whose morbidity is directly related to the severity of their congenital heart disease. Van der burgt et al diagnostic criteria have been used for the clinical diagnosis, karyotype studies have been performed to exclude chromosomal aberration disorders and patients DNA extraction for mutation studies have been obtained in some cases.
    [Show full text]
  • Detailed Characterization Of, and Clinical Correlations In, 10 Patients
    August 2008 ⅐ Vol. 10 ⅐ No. 8 article Detailed characterization of, and clinical correlations in, 10 patients with distal deletions of chromosome 9p Xueya Hauge, PhD1, Gordana Raca, PhD2, Sara Cooper, MS2, Kristin May, PhD3, Rhonda Spiro, MD4, Margaret Adam, MD2, and Christa Lese Martin, PhD2 Purpose: Deletions of distal 9p are associated with trigonocephaly, mental retardation, dysmorphic facial features, cardiac anomalies, and abnormal genitalia. Previous studies identified a proposed critical region for the consensus phenotype in band 9p23, between 11.8 Mb and 16 Mb from the 9p telomere. Here we report 10 new patients with 9p deletions; 9 patients have clinical features consistent with 9pϪ syndrome, but possess terminal deletions smaller than most reported cases, whereas one individual lacks the 9pϪ phenotype and shows a 140-kb interstitial telomeric deletion inherited from his mother. Methods: We combined fluorescence in situ hybridization and microarray analyses to delineate the size of each deletion. Results: The deletion sizes vary from 800 kb to 12.4 Mb in our patients with clinically relevant phenotypes. Clinical evaluation and comparison showed little difference in physical features with regard to the deletion sizes. Severe speech and language impairment were observed in all patients with clinically relevant phenotypes. Conclusion: The smallest deleted region common to our patients who demonstrate a phenotype consistent with 9pϪ is Ͻ2 Mb of 9pter, which contains six known genes. These genes may contribute to some of the cardinal features of 9p deletion syndrome. Genet Med 2008:10(8): 599–611. Key Words: 9p deletion, FISH, genotype-phenotype correlation, aCGH The 9p deletion syndrome is characterized by trigonoceph- points in 24 patients with visible 9p deletions and breakpoints aly, moderate to severe mental retardation, low-set, mal- at 9p22 or 9p23.
    [Show full text]
  • Sexual Dimorphism in Diverse Metazoans Is Regulated by a Novel Class of Intertwined Zinc Fingers
    Downloaded from genesdev.cshlp.org on October 4, 2021 - Published by Cold Spring Harbor Laboratory Press Sexual dimorphism in diverse metazoans is regulated by a novel class of intertwined zinc fingers Lingyang Zhu,1,4 Jill Wilken,2 Nelson B. Phillips,3 Umadevi Narendra,3 Ging Chan,1 Stephen M. Stratton,2 Stephen B. Kent,2 and Michael A. Weiss1,3–5 1Center for Molecular Oncology, Departments of Biochemistry & Molecular Biology and Chemistry, The University of Chicago, Chicago, Illinois 60637-5419 USA; 2Gryphon Sciences, South San Francisco, California 94080 USA; 3Department of Biochemistry, Case Western Reserve School of Medicine, Cleveland, Ohio 44106-4935 USA Sex determination is regulated by diverse pathways. Although upstream signals vary, a cysteine-rich DNA-binding domain (the DM motif) is conserved within downstream transcription factors of Drosophila melanogaster (Doublesex) and Caenorhabditis elegans (MAB-3). Vertebrate DM genes have likewise been identified and, remarkably, are associated with human sex reversal (46, XY gonadal dysgenesis). Here we demonstrate that the structure of the Doublesex domain contains a novel zinc module and disordered tail. The module consists of intertwined CCHC and HCCC Zn2+-binding sites; the tail functions as a nascent recognition ␣-helix. Mutations in either Zn2+-binding site or tail can lead to an intersex phenotype. The motif binds in the DNA minor groove without sharp DNA bending. These molecular features, unusual among zinc fingers and zinc modules, underlie the organization of a Drosophila enhancer that integrates sex- and tissue-specific signals. The structure provides a foundation for analysis of DM mutations affecting sexual dimorphism and courtship behavior.
    [Show full text]