MCID: CST001
MIFTS: 64

Costello Syndrome malady

Genetic diseases, Rare diseases, Neuronal diseases, Skin diseases, Fetal diseases, Cancer diseases categories

Summaries for Costello Syndrome

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22Genetics Home Reference, 44NIH Rare Diseases, 66Wikipedia, 48OMIM, 20GeneReviews, 34MalaCards
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NIH Rare Diseases:44 Costello syndrome is characterized by delayed development and intellectual disability, distinctive facial features, loose folds of extra skin (especially on the hands and feet), and unusually flexible joints. heart abnormalities are common, including an unusually fast heartbeat (tachycardia), structural heart defects, and a form of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). beginning in early childhood, people with costello syndrome are at an increased risk of developing certain cancerous and noncancerous tumors. costello syndrome is caused by mutations in the hras gene. it is considered an autosomal dominant condition, but almost all reported cases have resulted from new gene mutations and have occurred in people with no history of the disorder in their family. the signs and symptoms of costello syndrome overlap significantly with those of two other genetic conditions, cardiofaciocutaneous (cfc) syndrome and noonan syndrome. while the three conditions are distinguished by their genetic cause and specific patterns of signs and symptoms, it can be difficult to tell them apart in infancy. last updated: 5/24/2011

MalaCards: Costello Syndrome, also known as faciocutaneoskeletal syndrome, is related to cutis laxa and noonan syndrome, and has symptoms including enamel anomaly, ventricular septal defect/interventricular communication and pulmonary valve atresia/stenosis/narrowing. An important gene associated with Costello Syndrome is HRAS (Harvey rat sarcoma viral oncogene homolog), and among its related pathways are Chronic myeloid leukemia and G protein signaling Ras family GTPases in kinase cascades scheme . The compounds trifluoroethanol and vgvapg have been mentioned in the context of this disorder. Affiliated tissues include skin, heart and testes, and related mouse phenotypes are craniofacial and tumorigenesis.

Genetics Home Reference:22 Costello syndrome is a disorder that affects many parts of the body. This condition is characterized by delayed development and intellectual disability, loose folds of skin (which are especially noticeable on the hands and feet), unusually flexible joints, and distinctive facial features including a large mouth. Heart problems are common, including an abnormal heartbeat (arrhythmia), structural heart defects, and a type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Infants with Costello syndrome may be larger than average at birth, but most have difficulty feeding and grow more slowly than other children. People with this condition have relatively short stature and may have reduced growth hormone levels. Other signs and symptoms of Costello syndrome can include tight Achilles tendons (which connect the calf muscles to the heel), weak muscle tone (hypotonia), a structural abnormality of the brain called a Chiari I malformation, skeletal abnormalities, dental problems, and problems with vision.

Wikipedia:66 Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare genetic disorder... more...

Description from OMIM:48 218040

GeneReviews summary for costello

Aliases & Classifications for Costello Syndrome

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Sources:
9Disease Ontology, 20GeneReviews, 44NIH Rare Diseases, 21GeneTests, 23GTR, 22Genetics Home Reference, 48OMIM, 11DISEASES, 50Orphanet, 63UMLS, 36MeSH, 37MESH via Orphanet, 27ICD10 via Orphanet, 60SNOMED-CT via Orphanet, 64UMLS via Orphanet
See all sources

Classifications:



Characteristics (Orphanet epidemiological data):

50
costello syndrome:
Inheritance: Autosomal dominant,Sporadic; Age of onset: Neonatal/infancy


Aliases & Descriptions:

costello syndrome 9 20 44 21 23 22 48 11 50 63
faciocutaneoskeletal syndrome 9 44 22 50
fcs syndrome 9 44 22 50
intellectual disability - nasal papillomata 50


External Ids:

Disease Ontology9 DOID:0050469
OMIM48 218040
MeSH36 D056685
MESH via Orphanet37 D056685
ICD10 via Orphanet27 Q87.8
SNOMED-CT via Orphanet60 309776008
UMLS via Orphanet64 C0587248

Related Diseases for Costello Syndrome

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18GeneCards, 19GeneDecks
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Graphical network of the top 20 diseases related to Costello Syndrome:



Diseases related to costello syndrome

Symptoms for Costello Syndrome

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48OMIM, 50Orphanet
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Symptoms by clinical synopsis from OMIM:

218040

Clinical features from OMIM:

218040

Symptoms:

50 (show all 46)
  • enamel anomaly
  • ventricular septal defect/interventricular communication
  • pulmonary valve atresia/stenosis/narrowing
  • excess nuchal skin without pterygium colli
  • polyhydramnios
  • mitral valve prolapse/incompetence/insufficiency/regurgitation/ring anomaly
  • thin/hypoplastic toenails
  • thin/hypoplastic/hyperconvex fingernails
  • loose skin/skin relaxation/excess skin/creases
  • acanthosis nigricans
  • failure to thrive/difficulties for feeding in infancy/growth delay
  • antenatal exposure : alcohol
  • woolly/frizzy hair
  • keratoconus/keratoglobus
  • thick/wide ear lobe
  • hair and scalp anomalies
  • ulnar deviation of fingers
  • diffuse/generalised skin hyperpigmentation/melanoderma
  • abnormal dermatoglyphics
  • undescended/ectopic testes/cryptorchidia/unfixed testes
  • tendon rupture/tendinitis/bursitis/tenosynovitis
  • delayed bone age
  • macroglossia/tongue protrusion/proeminent/hypertrophic
  • depressed nasal bridge
  • coarse face
  • high vaulted/narrow palate
  • feeding disorder/dysphagia/swallowing/sucking disorder/esophageal dyskinesia
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • large face
  • cortical atrophy without hydrocephaly/cerebral hemiatrophy/subcortical atrophy
  • short neck
  • low set ears/posteriorly rotated ears
  • anomalies of skin, subcutaneous tissue and mucosae
  • abnormal dentition/dental position/implantation/unerupted/dental ankylosis
  • strabismus/squint
  • hyperextensible joints/articular hyperlaxity
  • tight skin/lack of elasticity
  • epicanthic folds
  • warts/papillomas
  • broad cheeks/cherub-like/cherubin face
  • cardiomyopathy/hypertrophic/dilated
  • hyperkeratosis/ainhum/hyperkeratotic skin fissures
  • gastroesophageal reflux/pyrosis/esophagitis/hiatal hernia/gastroparesia
  • short stature/dwarfism/nanism
  • thick lips
  • macrocephaly/macrocrania/megalocephaly/megacephaly

Drugs & Therapeutics for Costello Syndrome

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Sources:
6CenterWatch, 43NIH Clinical Center, 7ClinicalTrials
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Approved drugs:

Search CenterWatch for Costello Syndrome

Drug clinical trials:

Search ClinicalTrials for Costello Syndrome

Search NIH Clinical Center for Costello Syndrome

Search CenterWatch for Costello Syndrome

Genetic Tests for Costello Syndrome

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21GeneTests, 23GTR
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Genetic tests related to Costello Syndrome:

id Genetic test Affiliating Genes
1 Costello Syndrome21 23 HRAS

Anatomical Context for Costello Syndrome

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34MalaCards
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MalaCards organs/tissues related to Costello Syndrome:

34
Skin, Heart, Testes, Bone, Tongue, Brain, Pancreatic islet, Spinal cord

Animal Models for Costello Syndrome or affiliated genes

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38MGI
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MGI Mouse Phenotypes related to Costello Syndrome:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053828.9HRAS, MAP2K2, FBLN5
2MP:00020068.6HRAS, MAP2K2, FBLN5
3MP:00053908.0ELN, MAP2K2, GLB1, HRAS
4MP:00053767.5HRAS, GLB1, MAP2K2, ELN, FBLN5

Publications for Costello Syndrome

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53PubMed
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Articles related to Costello Syndrome:

(show top 50)    (show all 183)
idTitleAuthorsYear
1
Abnormal Ras signaling in Costello syndrome (CS) negatively regulates enamel formation. (24057668)
2014
2
Decreased bone mineral density in Costello syndrome. (24246682)
2014
3
Orthopedic manifestations and implications for individuals with Costello syndrome. (23813656)
2013
4
Antioxidant effects of potassium ascorbate with ribose in costello syndrome. (23393369)
2013
5
Two new cases with Costello syndrome. (24021445)
2013
6
High incidence of progressive postnatal cerebellar enlargement in Costello syndrome: brain overgrowth associated with HRAS mutations as the likely cause of structural brain and spinal cord abnormalities. (20425820)
2010
7
Progressively worsening hypertrophic cardiomyopathy in a child with newly diagnosed Costello syndrome while receiving growth hormone therapy. (20307337)
2010
8
Prenatal features of Costello syndrome: ultrasonographic findings and atrial tachycardia. (19382114)
2009
9
Germline expression of H-Ras(G12V) causes neurological deficits associated to Costello syndrome. (18823404)
2009
10
A premature infant with Costello syndrome due to a rare G13C HRAS mutation. (19213030)
2009
11
Longitudinal course of cognitive, adaptive, and behavioral characteristics in Costello syndrome. (19919001)
2009
12
Medical and surgical perspectives of cardiac hypertrophy in Costello syndrome. (19825250)
2009
13
Clarification of previously reported Costello syndrome patients. (18302240)
2008
14
The diagnosis of Costello syndrome: nomenclature in Ras/MAPK pathway disorders. (18386799)
2008
15
Costello syndrome associated with novel germline HRAS mutations: an attenuated phenotype? (18247425)
2008
16
A mouse model for Costello syndrome reveals an Ang II-mediated hypertensive condition. (18483625)
2008
17
Rapidly progressive scoliosis after successful treatment for osteopenia in Costello syndrome. (18203173)
2008
18
Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome. (17704260)
2007
19
Further delineation of the phenotype resulting from BRAF or MEK1 germline mutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome. (17551924)
2007
20
Costello syndrome. (18032860)
2007
21
Uniparental disomy at chromosome 11p15.5 followed by HRAS mutations in embryonal rhabdomyosarcoma: lessons from Costello syndrome. (17164262)
2007
22
Somatic mosaicism for an HRAS mutation causes Costello syndrome. (16969868)
2006
23
Obstructive sleep apnea in Costello syndrome. (16419102)
2006
24
Significant decrease in tropoelastin gene expression in fibroblasts from a Japanese Costello syndrome patient with impaired elastogenesis and enhanced proliferation. (16829682)
2006
25
Costello syndrome and hyperinsulinemic hypoglycemia. (16278907)
2005
26
Adaptive skills, cognitive, and behavioral characteristics of Costello syndrome. (15264285)
2004
27
Is growth hormone treatment beneficial or harmful in Costello syndrome? (12807973)
2003
28
What syndrome is this? Costello syndrome. (14521568)
2003
29
Studies on the pathogenesis of Costello syndrome. (12676910)
2003
30
Anaesthetic implications of Costello syndrome. (12641690)
2003
31
Concerning "Five additional Costello syndrome patients with rhabdomyosarcoma: proposal for a tumor screening protocol". (12698963)
2003
32
Costello syndrome: an overview. (12561057)
2003
33
Anaesthesiological considerations in Costello syndrome. (11982853)
2002
34
A case of Costello syndrome and glycogen storage disease type III. (11836377)
2002
35
Growth hormone deficiency in Costello syndrome: a possible explanation for the short stature. (11148542)
2001
36
Decreased elastin deposition and high proliferation of fibroblasts from Costello syndrome are related to functional deficiency in the 67-kD elastin-binding protein. (10712202)
2000
37
Costello syndrome: report of six patients including one with an embryonal rhabdomyosarcoma. (10664222)
2000
38
Picture of the month. Costello syndrome. (10850515)
2000
39
Second case of bladder carcinoma in a patient with Costello syndrome. (10678668)
2000
40
Costello syndrome with decreased gene expression of elastin in cultured dermal fibroblasts. (11146354)
2000
41
Costello syndrome. (9541110)
1998
42
Life-threatening cardiac involvement throughout life in a case of Costello syndrome. (9001809)
1996
43
Costello syndrome. (7722055)
1995
44
Costello syndrome: the natural history of a true postnatal growth retardation syndrome. (7546454)
1995
45
Hungarian case with Costello syndrome and translocation t(1,22) (7677162)
1995
46
Genetics of the Costello syndrome. (7528974)
1994
47
A Japanese patient with the Costello syndrome. (8168845)
1994
48
Cutis laxa: a feature of Costello syndrome. (7512146)
1994
49
Cutis laxa and the Costello syndrome. (8411045)
1993
50
Report on two patients with Costello syndrome and sialuria. (8291534)
1993

Variations for Costello Syndrome

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65UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar)
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UniProtKB/Swiss-Prot genetic disease variations for Costello Syndrome:

65 (show all 16)
id Symbol AA change Variation ID SNP ID
1HRASp.Gly12ValVAR_006836
2HRASp.Gly12ValVAR_006836
3HRASp.Gly12SerVAR_006837
4HRASp.Gly12SerVAR_006837
5HRASp.Gly12AlaVAR_026106
6HRASp.Gly13CysVAR_026107
7HRASp.Gly13AspVAR_026108
8HRASp.Gly12CysVAR_045975
9HRASp.Gly12GluVAR_045976
10HRASp.Gln22LysVAR_045977
11HRASp.Thr58IleVAR_045978
12HRASp.Glu63LysVAR_045980
13HRASp.Lys117ArgVAR_045981
14HRASp.Ala146ThrVAR_045982
15HRASp.Ala146ValVAR_045983
16HRASp.Gly12AspVAR_068816

Clinvar genetic disease variations for Costello Syndrome:

1 (show all 14)
id Gene Name Type Significance SNP ID Assembly Location
1HRASNM_005343.2(HRAS): c.187_207dup21 (p.Asp69_Gln70insGluTyrSerAlaMetArgAsp)duplicationPathogenicGRCh38Chr 11, 533849: 533869
2HRASNM_005343.2(HRAS): c.35G> T (p.Gly12Val)single nucleotide variantPathogenicrs104894230GRCh37Chr 11, 534288: 534288
3HRASNM_005343.2(HRAS): c.34G> A (p.Gly12Ser)single nucleotide variantPathogenicrs104894229GRCh37Chr 11, 534289: 534289
4HRASNM_005343.2(HRAS): c.35G> C (p.Gly12Ala)single nucleotide variantPathogenicrs104894230GRCh37Chr 11, 534288: 534288
5HRASNM_005343.2(HRAS): c.38G> A (p.Gly13Asp)single nucleotide variantPathogenicrs104894226GRCh37Chr 11, 534285: 534285
6HRASNM_005343.2(HRAS): c.350A> G (p.Lys117Arg)single nucleotide variantPathogenicrs104894227GRCh37Chr 11, 533553: 533553
7HRASNM_005343.2(HRAS): c.37G> T (p.Gly13Cys)single nucleotide variantPathogenicrs104894228GRCh37Chr 11, 534286: 534286
8HRASNM_005343.2(HRAS): c.436G> A (p.Ala146Thr)single nucleotide variantPathogenicrs104894231GRCh37Chr 11, 533467: 533467
9HRASNM_005343.2(HRAS): c.173C> T (p.Thr58Ile)single nucleotide variantPathogenicrs121917758GRCh37Chr 11, 533883: 533883
10HRASNM_005343.2(HRAS): c.437C> T (p.Ala146Val)single nucleotide variantPathogenicrs121917759GRCh37Chr 11, 533466: 533466
11HRASNM_005343.2(HRAS): c.35G> A (p.Gly12Asp)single nucleotide variantPathogenicrs104894230GRCh37Chr 11, 534288: 534288
12HRASNM_005343.2(HRAS): c.34G> T (p.Gly12Cys)single nucleotide variantPathogenicrs104894229GRCh37Chr 11, 534289: 534289
13HRASNM_005343.2(HRAS): c.110_111+1dupAGGduplicationPathogenicrs398122808GRCh37Chr 11, 534211: 534213
14HRASNM_005343.2(HRAS): c.108_110dupAGA (p.Glu37_Asp38insGlu)duplicationPathogenicrs398122809GRCh37Chr 11, 534213: 534215

Expression for genes affiliated with Costello Syndrome

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2BioGPS, 16Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Costello Syndrome

Search GEO for disease gene expression data for Costello Syndrome.

Pathways for genes affiliated with Costello Syndrome

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Sources:
51PathCards, 31KEGG, 61Thomson Reuters, 39NCBI BioSystems Database, 56Reactome, 54QIAGEN, 58SinoBiological, 62Tocris Bioscience, 13EMD Millipore, 52PharmGKB
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Pathways related to Costello Syndrome according to GeneCards/GeneDecks:

(show top 50)    (show all 67)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.4HRAS, MAP2K2
2
Show member pathways
MAPK Cascade39
Immune response Oncostatin M signaling via MAPK in human cells61
Oncostatin M Signaling Pathway39
9.4HRAS, MAP2K2
39.4MAP2K2, HRAS
4
Show member pathways
9.4MAP2K2, HRAS
59.4HRAS, MAP2K2
69.4MAP2K2, HRAS
7
Show member pathways
9.4HRAS, MAP2K2
8
Show member pathways
9.4HRAS, MAP2K2
9
Show member pathways
9.4HRAS, MAP2K2
10
Show member pathways
Signaling events mediated by Stem cell factor receptor (c-Kit)39
9.4MAP2K2, HRAS
11
Show member pathways
Development A2B receptor action via G protein alpha s61
9.4MAP2K2, HRAS
12
Show member pathways
9.4MAP2K2, HRAS
13
Show member pathways
9.4HRAS, MAP2K2
14
Show member pathways
9.4MAP2K2, HRAS
15
Show member pathways
Development Ligand independent activation of ESR1 and ESR261
9.4MAP2K2, HRAS
169.4HRAS, MAP2K2
17
Show member pathways
Signal transduction PTEN pathway61
9.4HRAS, MAP2K2
18
Show member pathways
9.4HRAS, MAP2K2
199.4MAP2K2, HRAS
20
Show member pathways
Development Beta adrenergic receptors regulation of ERK61
G protein signaling G Protein alpha s signaling cascades61
G protein signaling G Protein beta gamma signaling cascades61
9.4MAP2K2, HRAS
21
Show member pathways
Development A1 receptor signaling61
G protein signaling G Protein alpha q signaling cascades61
9.4HRAS, MAP2K2
22
Show member pathways
Prostate Cancer39
Integrated Cancer pathway39
Steroid Biosynthesis39
9.4MAP2K2, HRAS
23
Show member pathways
Immune response IL 4 signaling pathway61
Signal transduction AKT signaling61
9.4MAP2K2, HRAS
24
Show member pathways
ErbB receptor signaling network39
ErbB signaling pathway39
9.4HRAS, MAP2K2
25
Show member pathways
9.4HRAS, MAP2K2
26
Show member pathways
Development Flt3 signaling61
9.4MAP2K2, HRAS
279.4MAP2K2, HRAS
28
Show member pathways
Development VEGF signaling via VEGFR2 generic cascades61
9.4MAP2K2, HRAS
29
Show member pathways
EPO Receptor Signaling39
EPO signaling pathway39
9.4MAP2K2, HRAS
309.4HRAS, MAP2K2
319.4MAP2K2, HRAS
32
Show member pathways
9.4MAP2K2, HRAS
339.4HRAS, MAP2K2
349.4HRAS, MAP2K2
35
Show member pathways
9.4MAP2K2, HRAS
369.4HRAS, MAP2K2
37
Show member pathways
IL-2 Signaling pathway39
9.4MAP2K2, HRAS
38
Show member pathways
9.4MAP2K2, HRAS
399.4HRAS, MAP2K2
40
Show member pathways
9.4HRAS, MAP2K2
419.4MAP2K2, HRAS
42
Show member pathways
Development Activation of ERK by Alpha 1 adrenergic receptors61
9.4HRAS, MAP2K2
439.4HRAS, MAP2K2
449.4HRAS, MAP2K2
45
Show member pathways
Immune response IL 3 activation and signaling pathway61
9.4HRAS, MAP2K2
46
Show member pathways
9.4MAP2K2, HRAS
47
Show member pathways
9.4HRAS, MAP2K2
48
Show member pathways
9.1ELN, FBLN5
49
Show member pathways
8.6HRAS, MAP2K2, ELN
50
Show member pathways
8.6HRAS, MAP2K2, ELN

Compounds for genes affiliated with Costello Syndrome

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46Novoseek, 12DrugBank, 25HMDB
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Compounds related to Costello Syndrome according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1trifluoroethanol46 1210.3HRAS, ELN
2vgvapg469.3GLB1, ELN
3keratan sulfate469.3GLB1, ELN
4tetrapeptide469.3HRAS, ELN
5valine469.2HRAS, ELN
6lactose46 1210.1ELN, GLB1
7chondroitin sulfate46 2510.0GLB1, ELN
8vegf468.4HRAS, ELN, FBLN5

GO Terms for genes affiliated with Costello Syndrome

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17Gene Ontology
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Cellular components related to Costello Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1elastic fiberGO:0719539.0ELN, FBLN5
2Golgi apparatusGO:0057948.9HRAS, GLB1, MAP2K2
3perinuclear region of cytoplasmGO:0484718.6HRAS, GLB1, MAP2K2

Biological processes related to Costello Syndrome according to GeneCards/GeneDecks:

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1activation of MAPKK activityGO:0001869.5HRAS, MAP2K2
2MAPK cascadeGO:0001659.5HRAS, MAP2K2
3Ras protein signal transductionGO:0072659.5HRAS, MAP2K2
4Fc-epsilon receptor signaling pathwayGO:0380959.4HRAS, MAP2K2
5insulin receptor signaling pathwayGO:0082869.3HRAS, MAP2K2
6organ morphogenesisGO:0098879.2ELN, HRAS
7fibroblast growth factor receptor signaling pathwayGO:0085439.1HRAS, MAP2K2

Molecular functions related to Costello Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1protein C-terminus bindingGO:0080229.5HRAS, FBLN5
2protein bindingGO:0055157.2HRAS, GLB1, MAP2K2, ELN, FBLN5

Products for genes affiliated with Costello Syndrome

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  • Antibodies
  • Proteins
  • Lysates
  • Antibodies

Sources for Costello Syndrome

About this section
4CDC
14ExPASy
15FMA
23GTR
24HGMD
25HMDB
26ICD10
27ICD10 via Orphanet
28ICD9CM
30IUPHAR
31KEGG
36MeSH
37MESH via Orphanet
38MGI
41NCIt
42NDF-RT
45NINDS
46Novoseek
48OMIM
49OMIM via Orphanet
53PubMed
54QIAGEN
60SNOMED-CT via Orphanet
63UMLS
64UMLS via Orphanet