MCID: CST001
MIFTS: 64

Costello Syndrome malady

Genetic diseases, Rare diseases, Neuronal diseases, Skin diseases, Fetal diseases, Cancer diseases categories
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Summaries for Costello Syndrome

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Sources:
21Genetics Home Reference, 43NIH Rare Diseases, 65Wikipedia, 47OMIM, 19GeneReviews, 33MalaCards
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NIH Rare Diseases:43 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:21 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:65 Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare genetic disorder... more...

Description from OMIM:47 218040

GeneReviews summary for costello

Aliases & Classifications for Costello Syndrome

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Sources:
8Disease Ontology, 19GeneReviews, 43NIH Rare Diseases, 20GeneTests, 22GTR, 21Genetics Home Reference, 47OMIM, 10DISEASES, 49Orphanet, 62UMLS, 35MeSH, 36MESH via Orphanet, 26ICD10 via Orphanet, 59SNOMED-CT via Orphanet, 63UMLS via Orphanet
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Classifications:



Characteristics (Orphanet epidemiological data):

49
costello syndrome:
Inheritance: Autosomal dominant,Sporadic; Age of onset: Neonatal/infancy


Aliases & Descriptions:

costello syndrome 8 19 43 20 22 21 47 10 49 62
faciocutaneoskeletal syndrome 8 43 21 49
fcs syndrome 8 43 21 49
intellectual disability - nasal papillomata 49


External Ids:

Disease Ontology8 DOID:0050469
OMIM47 218040
MeSH35 D056685
MESH via Orphanet36 D056685
ICD10 via Orphanet26 Q87.8
SNOMED-CT via Orphanet59 309776008
UMLS via Orphanet63 C0587248

Related Diseases for Costello Syndrome

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17GeneCards, 18GeneDecks
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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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47OMIM, 49Orphanet
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Symptoms by clinical synopsis from OMIM:

218040

Clinical features from OMIM:

218040

Symptoms:

49 (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:
42NIH Clinical Center, 6ClinicalTrials
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Drug clinical trials:

Search ClinicalTrials for Costello Syndrome

Search NIH Clinical Center for Costello Syndrome

Genetic Tests for Costello Syndrome

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20GeneTests, 22GTR
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Genetic tests related to Costello Syndrome:

id Genetic test Affiliating Genes
1 Costello Syndrome20 22 HRAS

Anatomical Context for Costello Syndrome

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33MalaCards
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MalaCards organs/tissues related to Costello Syndrome:

33
Skin, Heart, Testes, Bone, Tongue, Brain, Pancreatic islet, Spinal cord

Animal Models for Costello Syndrome or affiliated genes

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37MGI
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MGI Mouse Phenotypes related to Costello Syndrome:

37
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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52PubMed
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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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64UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar)
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UniProtKB/Swiss-Prot genetic disease variations for Costello Syndrome:

64 (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, 15Gene 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:
50PathCards, 30KEGG, 60Thomson Reuters, 38NCBI BioSystems Database, 55Reactome, 53QIAGEN, 57SinoBiological, 61Tocris Bioscience, 12EMD Millipore, 51PharmGKB
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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 Cascade38
Immune response Oncostatin M signaling via MAPK in human cells60
Oncostatin M Signaling Pathway38
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)38
9.4MAP2K2, HRAS
11
Show member pathways
Development A2B receptor action via G protein alpha s60
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 ESR260
9.4MAP2K2, HRAS
169.4HRAS, MAP2K2
17
Show member pathways
Signal transduction PTEN pathway60
9.4HRAS, MAP2K2
18
Show member pathways
9.4HRAS, MAP2K2
199.4MAP2K2, HRAS
20
Show member pathways
Development Beta adrenergic receptors regulation of ERK60
G protein signaling G Protein alpha s signaling cascades60
G protein signaling G Protein beta gamma signaling cascades60
9.4MAP2K2, HRAS
21
Show member pathways
Development A1 receptor signaling60
G protein signaling G Protein alpha q signaling cascades60
9.4HRAS, MAP2K2
22
Show member pathways
Prostate Cancer38
Integrated Cancer pathway38
Steroid Biosynthesis38
9.4MAP2K2, HRAS
23
Show member pathways
Immune response IL 4 signaling pathway60
Signal transduction AKT signaling60
9.4MAP2K2, HRAS
24
Show member pathways
ErbB receptor signaling network38
ErbB signaling pathway38
9.4HRAS, MAP2K2
25
Show member pathways
9.4HRAS, MAP2K2
26
Show member pathways
Development Flt3 signaling60
9.4MAP2K2, HRAS
279.4MAP2K2, HRAS
28
Show member pathways
Development VEGF signaling via VEGFR2 generic cascades60
9.4MAP2K2, HRAS
29
Show member pathways
EPO Receptor Signaling38
EPO signaling pathway38
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 pathway38
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 receptors60
9.4HRAS, MAP2K2
439.4HRAS, MAP2K2
449.4HRAS, MAP2K2
45
Show member pathways
Immune response IL 3 activation and signaling pathway60
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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Sources:
45Novoseek, 11DrugBank, 24HMDB
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Compounds related to Costello Syndrome according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1trifluoroethanol45 1110.3HRAS, ELN
2vgvapg459.3GLB1, ELN
3keratan sulfate459.3GLB1, ELN
4tetrapeptide459.3HRAS, ELN
5valine459.2HRAS, ELN
6lactose45 1110.1ELN, GLB1
7chondroitin sulfate45 2410.0GLB1, ELN
8vegf458.4HRAS, ELN, FBLN5

GO Terms for genes affiliated with Costello Syndrome

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16Gene 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
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Sources for Costello Syndrome

About this section
4CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
29IUPHAR
30KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
52PubMed
53QIAGEN
59SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet