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Edinburgh malformation syndrome

MedGen UID:
167084
Concept ID:
C0795933
Disease or Syndrome
Synonym: Edinburgh Malformation Syndrome
SNOMED CT: Typus Edinburgensis (771178004); Edinburgh malformation syndrome (771178004)
Modes of inheritance:
Unknown inheritance
MedGen UID:
989040
Concept ID:
CN307042
Finding
Source: Orphanet
Hereditary clinical entity whose mode of inheritance is unknown.
 
Monarch Initiative: MONDO:0007519
OMIM®: 129850
Orphanet: ORPHA1895

Definition

A rare genetic lethal multiple congenital anomalies/dysmorphic syndrome characterized by consistently abnormal facial appearance, true or apparent hydrocephalus, motor and cognitive developmental delay, failure to thrive (feeding difficulties, vomiting, chest infections) and death within a few months of birth. Carp mouth, hairiness of the forehead, neonatal hyperbilirubinemia and advanced bone age may also be associated. There have been no further descriptions in the literature since 1991. [from SNOMEDCT_US]

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Accelerated skeletal maturation
MedGen UID:
154262
Concept ID:
C0545053
Finding
An abnormally increased rate of skeletal maturation. Accelerated skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Neonatal hyperbilirubinemia
MedGen UID:
208991
Concept ID:
C0857007
Disease or Syndrome
A type of hyperbilirubinemia with neonatal onset.
U-Shaped upper lip vermilion
MedGen UID:
383857
Concept ID:
C1856202
Finding
Gentle upward curve of the upper lip vermilion such that the center is placed well superior to the commissures.
Frontal hirsutism
MedGen UID:
333413
Concept ID:
C1839830
Finding
Excessive amount of hair growth on forehead.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVEdinburgh malformation syndrome

Professional guidelines

PubMed

Douzgou S, Rawson M, Baselga E, Danielpour M, Faivre L, Kashanian A, Keppler-Noreuil KM, Kuentz P, Mancini GMS, Maniere MC, Martinez-Glez V, Parker VE, Semple RK, Srivastava S, Vabres P, De Wit MY, Graham JM Jr, Clayton-Smith J, Mirzaa GM, Biesecker LG
Clin Genet 2022 Jan;101(1):32-47. Epub 2021 Jul 16 doi: 10.1111/cge.14027. PMID: 34240408Free PMC Article
Kline AD, Moss JF, Selicorni A, Bisgaard AM, Deardorff MA, Gillett PM, Ishman SL, Kerr LM, Levin AV, Mulder PA, Ramos FJ, Wierzba J, Ajmone PF, Axtell D, Blagowidow N, Cereda A, Costantino A, Cormier-Daire V, FitzPatrick D, Grados M, Groves L, Guthrie W, Huisman S, Kaiser FJ, Koekkoek G, Levis M, Mariani M, McCleery JP, Menke LA, Metrena A, O'Connor J, Oliver C, Pie J, Piening S, Potter CJ, Quaglio AL, Redeker E, Richman D, Rigamonti C, Shi A, Tümer Z, Van Balkom IDC, Hennekam RC
Nat Rev Genet 2018 Oct;19(10):649-666. doi: 10.1038/s41576-018-0031-0. PMID: 29995837Free PMC Article
Espay AJ, Aybek S, Carson A, Edwards MJ, Goldstein LH, Hallett M, LaFaver K, LaFrance WC Jr, Lang AE, Nicholson T, Nielsen G, Reuber M, Voon V, Stone J, Morgante F
JAMA Neurol 2018 Sep 1;75(9):1132-1141. doi: 10.1001/jamaneurol.2018.1264. PMID: 29868890Free PMC Article

Recent clinical studies

Etiology

Mill P, Christensen ST, Pedersen LB
Nat Rev Genet 2023 Jul;24(7):421-441. Epub 2023 Apr 18 doi: 10.1038/s41576-023-00587-9. PMID: 37072495Free PMC Article
Butler G, Srirangalingam U, Faithfull J, Sangster P, Senniappan S, Mitchell R
Arch Dis Child 2023 Mar;108(3):166-171. Epub 2022 Aug 10 doi: 10.1136/archdischild-2020-320831. PMID: 35948402Free PMC Article
Senum SR, Li YSM, Benson KA, Joli G, Olinger E, Lavu S, Madsen CD, Gregory AV, Neatu R, Kline TL, Audrézet MP, Outeda P, Nau CB, Meijer E, Ali H, Steinman TI, Mrug M, Phelan PJ, Watnick TJ, Peters DJM, Ong ACM, Conlon PJ, Perrone RD, Cornec-Le Gall E, Hogan MC, Torres VE, Sayer JA; Genomics England Research Consortium, the HALT PKD, CRISP, DIPAK, ADPKD Modifier, and TAME PKD studies, Harris PC
Am J Hum Genet 2022 Jan 6;109(1):136-156. Epub 2021 Dec 9 doi: 10.1016/j.ajhg.2021.11.016. PMID: 34890546Free PMC Article
Douzgou S, Rawson M, Baselga E, Danielpour M, Faivre L, Kashanian A, Keppler-Noreuil KM, Kuentz P, Mancini GMS, Maniere MC, Martinez-Glez V, Parker VE, Semple RK, Srivastava S, Vabres P, De Wit MY, Graham JM Jr, Clayton-Smith J, Mirzaa GM, Biesecker LG
Clin Genet 2022 Jan;101(1):32-47. Epub 2021 Jul 16 doi: 10.1111/cge.14027. PMID: 34240408Free PMC Article
Kline AD, Moss JF, Selicorni A, Bisgaard AM, Deardorff MA, Gillett PM, Ishman SL, Kerr LM, Levin AV, Mulder PA, Ramos FJ, Wierzba J, Ajmone PF, Axtell D, Blagowidow N, Cereda A, Costantino A, Cormier-Daire V, FitzPatrick D, Grados M, Groves L, Guthrie W, Huisman S, Kaiser FJ, Koekkoek G, Levis M, Mariani M, McCleery JP, Menke LA, Metrena A, O'Connor J, Oliver C, Pie J, Piening S, Potter CJ, Quaglio AL, Redeker E, Richman D, Rigamonti C, Shi A, Tümer Z, Van Balkom IDC, Hennekam RC
Nat Rev Genet 2018 Oct;19(10):649-666. doi: 10.1038/s41576-018-0031-0. PMID: 29995837Free PMC Article

Diagnosis

Butler G, Srirangalingam U, Faithfull J, Sangster P, Senniappan S, Mitchell R
Arch Dis Child 2023 Mar;108(3):166-171. Epub 2022 Aug 10 doi: 10.1136/archdischild-2020-320831. PMID: 35948402Free PMC Article
Singh T, Khan H, Gamble DT, Scally C, Newby DE, Dawson D
Circulation 2022 Mar 29;145(13):1002-1019. Epub 2022 Mar 28 doi: 10.1161/CIRCULATIONAHA.121.055854. PMID: 35344411Free PMC Article
Rice GI, Park S, Gavazzi F, Adang LA, Ayuk LA, Van Eyck L, Seabra L, Barrea C, Battini R, Belot A, Berg S, Billette de Villemeur T, Bley AE, Blumkin L, Boespflug-Tanguy O, Briggs TA, Brimble E, Dale RC, Darin N, Debray FG, De Giorgis V, Denecke J, Doummar D, Drake Af Hagelsrum G, Eleftheriou D, Estienne M, Fazzi E, Feillet F, Galli J, Hartog N, Harvengt J, Heron B, Heron D, Kelly DA, Lev D, Levrat V, Livingston JH, Marti I, Mignot C, Mochel F, Nougues MC, Oppermann I, Pérez-Dueñas B, Popp B, Rodero MP, Rodriguez D, Saletti V, Sharpe C, Tonduti D, Vadlamani G, Van Haren K, Tomas Vila M, Vogt J, Wassmer E, Wiedemann A, Wilson CJ, Zerem A, Zweier C, Zuberi SM, Orcesi S, Vanderver AL, Hur S, Crow YJ
Hum Mutat 2020 Apr;41(4):837-849. Epub 2020 Jan 14 doi: 10.1002/humu.23975. PMID: 31898846Free PMC Article
Kline AD, Moss JF, Selicorni A, Bisgaard AM, Deardorff MA, Gillett PM, Ishman SL, Kerr LM, Levin AV, Mulder PA, Ramos FJ, Wierzba J, Ajmone PF, Axtell D, Blagowidow N, Cereda A, Costantino A, Cormier-Daire V, FitzPatrick D, Grados M, Groves L, Guthrie W, Huisman S, Kaiser FJ, Koekkoek G, Levis M, Mariani M, McCleery JP, Menke LA, Metrena A, O'Connor J, Oliver C, Pie J, Piening S, Potter CJ, Quaglio AL, Redeker E, Richman D, Rigamonti C, Shi A, Tümer Z, Van Balkom IDC, Hennekam RC
Nat Rev Genet 2018 Oct;19(10):649-666. doi: 10.1038/s41576-018-0031-0. PMID: 29995837Free PMC Article
Espay AJ, Aybek S, Carson A, Edwards MJ, Goldstein LH, Hallett M, LaFaver K, LaFrance WC Jr, Lang AE, Nicholson T, Nielsen G, Reuber M, Voon V, Stone J, Morgante F
JAMA Neurol 2018 Sep 1;75(9):1132-1141. doi: 10.1001/jamaneurol.2018.1264. PMID: 29868890Free PMC Article

Therapy

Simpson M, Narwal A, West E, Martin J, Bagot CN, Page AR, Watson HG, Whyte CS, Mutch NJ
J Thromb Haemost 2023 Dec;21(12):3589-3596. Epub 2023 Sep 19 doi: 10.1016/j.jtha.2023.09.007. PMID: 37734715
Broderick C, Kobayashi S, Suto M, Ito S, Kobayashi T
Cochrane Database Syst Rev 2023 Jan 25;1(1):CD014884. doi: 10.1002/14651858.CD014884.pub2. PMID: 36695415Free PMC Article
Butler G, Srirangalingam U, Faithfull J, Sangster P, Senniappan S, Mitchell R
Arch Dis Child 2023 Mar;108(3):166-171. Epub 2022 Aug 10 doi: 10.1136/archdischild-2020-320831. PMID: 35948402Free PMC Article
Singh T, Khan H, Gamble DT, Scally C, Newby DE, Dawson D
Circulation 2022 Mar 29;145(13):1002-1019. Epub 2022 Mar 28 doi: 10.1161/CIRCULATIONAHA.121.055854. PMID: 35344411Free PMC Article
Espay AJ, Aybek S, Carson A, Edwards MJ, Goldstein LH, Hallett M, LaFaver K, LaFrance WC Jr, Lang AE, Nicholson T, Nielsen G, Reuber M, Voon V, Stone J, Morgante F
JAMA Neurol 2018 Sep 1;75(9):1132-1141. doi: 10.1001/jamaneurol.2018.1264. PMID: 29868890Free PMC Article

Prognosis

Stewart I, Jacob J, George PM, Molyneaux PL, Porter JC, Allen RJ, Aslani S, Baillie JK, Barratt SL, Beirne P, Bianchi SM, Blaikley JF, Chalmers JD, Chambers RC, Chadhuri N, Coleman C, Collier G, Denneny EK, Docherty A, Elneima O, Evans RA, Fabbri L, Gibbons MA, Gleeson FV, Gooptu B, Greening NJ, Guio BG, Hall IP, Hanley NA, Harris V, Harrison EM, Heightman M, Hillman TE, Horsley A, Houchen-Wolloff L, Jarrold I, Johnson SR, Jones MG, Khan F, Lawson R, Leavy O, Lone N, Marks M, McAuley H, Mehta P, Parekh D, Hanley KP, Platé M, Pearl J, Poinasamy K, Quint JK, Raman B, Richardson M, Rivera-Ortega P, Saunders L, Saunders R, Semple MG, Sereno M, Shikotra A, Simpson AJ, Singapuri A, Smith DJF, Spears M, Spencer LG, Stanel S, Thickett DR, Thompson AAR, Thorpe M, Walsh SLF, Walker S, Weatherley ND, Weeks ME, Wild JM, Wootton DG, Brightling CE, Ho LP, Wain LV, Jenkins GR
Am J Respir Crit Care Med 2023 Mar 15;207(6):693-703. doi: 10.1164/rccm.202203-0564OC. PMID: 36457159Free PMC Article
Rice GI, Park S, Gavazzi F, Adang LA, Ayuk LA, Van Eyck L, Seabra L, Barrea C, Battini R, Belot A, Berg S, Billette de Villemeur T, Bley AE, Blumkin L, Boespflug-Tanguy O, Briggs TA, Brimble E, Dale RC, Darin N, Debray FG, De Giorgis V, Denecke J, Doummar D, Drake Af Hagelsrum G, Eleftheriou D, Estienne M, Fazzi E, Feillet F, Galli J, Hartog N, Harvengt J, Heron B, Heron D, Kelly DA, Lev D, Levrat V, Livingston JH, Marti I, Mignot C, Mochel F, Nougues MC, Oppermann I, Pérez-Dueñas B, Popp B, Rodero MP, Rodriguez D, Saletti V, Sharpe C, Tonduti D, Vadlamani G, Van Haren K, Tomas Vila M, Vogt J, Wassmer E, Wiedemann A, Wilson CJ, Zerem A, Zweier C, Zuberi SM, Orcesi S, Vanderver AL, Hur S, Crow YJ
Hum Mutat 2020 Apr;41(4):837-849. Epub 2020 Jan 14 doi: 10.1002/humu.23975. PMID: 31898846Free PMC Article
Hickie IB, Scott EM, Cross SP, Iorfino F, Davenport TA, Guastella AJ, Naismith SL, Carpenter JS, Rohleder C, Crouse JJ, Hermens DF, Koethe D, Markus Leweke F, Tickell AM, Sawrikar V, Scott J
Med J Aust 2019 Nov;211 Suppl 9:S3-S46. doi: 10.5694/mja2.50383. PMID: 31679171
Espay AJ, Aybek S, Carson A, Edwards MJ, Goldstein LH, Hallett M, LaFaver K, LaFrance WC Jr, Lang AE, Nicholson T, Nielsen G, Reuber M, Voon V, Stone J, Morgante F
JAMA Neurol 2018 Sep 1;75(9):1132-1141. doi: 10.1001/jamaneurol.2018.1264. PMID: 29868890Free PMC Article
Horne AW, Alexander CI
J Fam Plann Reprod Health Care 2005 Apr;31(2):103-7. doi: 10.1783/1471189053629428. PMID: 15921544

Clinical prediction guides

Broderick C, Kobayashi S, Suto M, Ito S, Kobayashi T
Cochrane Database Syst Rev 2023 Jan 25;1(1):CD014884. doi: 10.1002/14651858.CD014884.pub2. PMID: 36695415Free PMC Article
Rice GI, Park S, Gavazzi F, Adang LA, Ayuk LA, Van Eyck L, Seabra L, Barrea C, Battini R, Belot A, Berg S, Billette de Villemeur T, Bley AE, Blumkin L, Boespflug-Tanguy O, Briggs TA, Brimble E, Dale RC, Darin N, Debray FG, De Giorgis V, Denecke J, Doummar D, Drake Af Hagelsrum G, Eleftheriou D, Estienne M, Fazzi E, Feillet F, Galli J, Hartog N, Harvengt J, Heron B, Heron D, Kelly DA, Lev D, Levrat V, Livingston JH, Marti I, Mignot C, Mochel F, Nougues MC, Oppermann I, Pérez-Dueñas B, Popp B, Rodero MP, Rodriguez D, Saletti V, Sharpe C, Tonduti D, Vadlamani G, Van Haren K, Tomas Vila M, Vogt J, Wassmer E, Wiedemann A, Wilson CJ, Zerem A, Zweier C, Zuberi SM, Orcesi S, Vanderver AL, Hur S, Crow YJ
Hum Mutat 2020 Apr;41(4):837-849. Epub 2020 Jan 14 doi: 10.1002/humu.23975. PMID: 31898846Free PMC Article
Vetrini F, McKee S, Rosenfeld JA, Suri M, Lewis AM, Nugent KM, Roeder E, Littlejohn RO, Holder S, Zhu W, Alaimo JT, Graham B, Harris JM, Gibson JB, Pastore M, McBride KL, Komara M, Al-Gazali L, Al Shamsi A, Fanning EA, Wierenga KJ, Scott DA, Ben-Neriah Z, Meiner V, Cassuto H, Elpeleg O, Holder JL Jr, Burrage LC, Seaver LH, Van Maldergem L, Mahida S, Soul JS, Marlatt M, Matyakhina L, Vogt J, Gold JA, Park SM, Varghese V, Lampe AK, Kumar A, Lees M, Holder-Espinasse M, McConnell V, Bernhard B, Blair E, Harrison V; DDD study, Muzny DM, Gibbs RA, Elsea SH, Posey JE, Bi W, Lalani S, Xia F, Yang Y, Eng CM, Lupski JR, Liu P
Genome Med 2019 Feb 28;11(1):12. doi: 10.1186/s13073-019-0623-0. PMID: 30819258Free PMC Article
Espay AJ, Aybek S, Carson A, Edwards MJ, Goldstein LH, Hallett M, LaFaver K, LaFrance WC Jr, Lang AE, Nicholson T, Nielsen G, Reuber M, Voon V, Stone J, Morgante F
JAMA Neurol 2018 Sep 1;75(9):1132-1141. doi: 10.1001/jamaneurol.2018.1264. PMID: 29868890Free PMC Article
Sifrim A, Hitz MP, Wilsdon A, Breckpot J, Turki SH, Thienpont B, McRae J, Fitzgerald TW, Singh T, Swaminathan GJ, Prigmore E, Rajan D, Abdul-Khaliq H, Banka S, Bauer UM, Bentham J, Berger F, Bhattacharya S, Bu'Lock F, Canham N, Colgiu IG, Cosgrove C, Cox H, Daehnert I, Daly A, Danesh J, Fryer A, Gewillig M, Hobson E, Hoff K, Homfray T; INTERVAL Study, Kahlert AK, Ketley A, Kramer HH, Lachlan K, Lampe AK, Louw JJ, Manickara AK, Manase D, McCarthy KP, Metcalfe K, Moore C, Newbury-Ecob R, Omer SO, Ouwehand WH, Park SM, Parker MJ, Pickardt T, Pollard MO, Robert L, Roberts DJ, Sambrook J, Setchfield K, Stiller B, Thornborough C, Toka O, Watkins H, Williams D, Wright M, Mital S, Daubeney PE, Keavney B, Goodship J; UK10K Consortium, Abu-Sulaiman RM, Klaassen S, Wright CF, Firth HV, Barrett JC, Devriendt K, FitzPatrick DR, Brook JD; Deciphering Developmental Disorders Study, Hurles ME
Nat Genet 2016 Sep;48(9):1060-5. Epub 2016 Aug 1 doi: 10.1038/ng.3627. PMID: 27479907Free PMC Article

Recent systematic reviews

Broderick C, Kobayashi S, Suto M, Ito S, Kobayashi T
Cochrane Database Syst Rev 2023 Jan 25;1(1):CD014884. doi: 10.1002/14651858.CD014884.pub2. PMID: 36695415Free PMC Article
Cetin Gedik K, Lamot L, Romano M, Demirkaya E, Piskin D, Torreggiani S, Adang LA, Armangue T, Barchus K, Cordova DR, Crow YJ, Dale RC, Durrant KL, Eleftheriou D, Fazzi EM, Gattorno M, Gavazzi F, Hanson EP, Lee-Kirsch MA, Montealegre Sanchez GA, Neven B, Orcesi S, Ozen S, Poli MC, Schumacher E, Tonduti D, Uss K, Aletaha D, Feldman BM, Vanderver A, Brogan PA, Goldbach-Mansky R
Arthritis Rheumatol 2022 May;74(5):735-751. Epub 2022 Mar 21 doi: 10.1002/art.42087. PMID: 35315249
Fetit R, Hillary RF, Price DJ, Lawrie SM
Neurosci Biobehav Rev 2021 Oct;129:35-62. Epub 2021 Jul 14 doi: 10.1016/j.neubiorev.2021.07.014. PMID: 34273379
De Luca C, Crow YJ, Rodero M, Rice GI, Ahmed M, Lammens M, De Cock P, Van Esch H, Lagae L, Rochtus A
Clin Genet 2020 Nov;98(5):423-432. Epub 2020 May 11 doi: 10.1111/cge.13761. PMID: 32333401
O'Leary L, Hughes-McCormack L, Dunn K, Cooper SA
J Appl Res Intellect Disabil 2018 Sep;31(5):687-708. Epub 2018 Mar 24 doi: 10.1111/jar.12446. PMID: 29573301

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