MCID: CST001
MIFTS: 67

Costello Syndrome

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Cardiovascular diseases, Skin diseases, Fetal diseases

Aliases & Classifications for Costello Syndrome

MalaCards integrated aliases for Costello Syndrome:

Name: Costello Syndrome 54 12 23 50 24 25 56 71 29 42 14 69
Faciocutaneoskeletal Syndrome 12 50 25 56 71
Fcs Syndrome 12 50 25 56 71
Congenital Myopathy with Excess of Muscle Spindles 54 71 13
Myopathy, Congenital, with Excess of Muscle Spindles 29 69
Cmems 71
Cstlo 71
Fcss 71

Characteristics:

Orphanet epidemiological data:

56
costello syndrome
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Japan); Age of onset: Antenatal,Neonatal;

OMIM:

54
Inheritance:
autosomal dominant
isolated cases

Miscellaneous:
sudden death
majority of cases are sporadic
associated with advanced paternal age
characteristic facial features become more apparent with age
phenotypic overlap with noonan syndrome 3 or cardiofaciocutaneous syndrome


HPO:

32
costello syndrome:
Mortality/Aging sudden death
Inheritance autosomal dominant inheritance sporadic


GeneReviews:

23
Penetrance Penetrance is complete [aoki et al 2005, estep et al 2006, gripp et al 2006a, kerr et al 2006]...

Classifications:



Summaries for Costello Syndrome

NIH Rare Diseases : 50 costello syndrome is a rare condition that affects many different parts of the body. signs and symptoms generally include developmental delay, intellectual disability, distinctive facial features, loose folds of extra skin (especially on the hands and feet), and unusually flexible joints. affected people may also have heart abnormalities such as tachycardia, structural heart defects, and hypertrophic cardiomyopathy. beginning in early childhood, people with costello syndrome additionally have an increased risk to develop certain cancerous and noncancerous tumors. costello syndrome is caused by changes (mutations) in the hras gene. it is considered an autosomal dominant condition, but almost all cases are the result of de novo gene mutations and occur in people with no family history of the condition. treatment is based on the signs and symptoms present in each person. costello syndrome belongs to a group of related conditions called the rasopathies. these conditions have some overlapping features and are all caused by genetic changes that disrupt the body's ras pathway, affecting growth and development. the features of costello syndrome overlap significantly with two of the rasopathies, cardiofaciocutaneous (cfc) syndrome and noonan syndrome. last updated: 3/9/2016

MalaCards based summary : Costello Syndrome, also known as faciocutaneoskeletal syndrome, is related to cardiofaciocutaneous syndrome and cutis laxa, autosomal dominant, and has symptoms including short stature, macroglossia and strabismus. An important gene associated with Costello Syndrome is HRAS (HRas Proto-Oncogene, GTPase), and among its related pathways/superpathways are HIV Life Cycle and TGF-Beta Pathway. The drug Anesthetics has been mentioned in the context of this disorder. Affiliated tissues include skin, heart and brain, and related phenotypes are Decreased cell migration and cardiovascular system

UniProtKB/Swiss-Prot : 71 Congenital myopathy with excess of muscle spindles: Variant of Costello syndrome. Costello syndrome: A rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.

Genetics Home Reference : 25 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.

OMIM : 54
Costello syndrome is a rare multiple congenital anomaly syndrome associated in all cases with a characteristic coarse facies, short stature, distinctive hand posture and appearance, severe feeding difficulty, and failure to thrive. Other features include cardiac anomalies and developmental disability. Facial warts, particularly nasolabial, are often present in childhood (Kerr et al., 2006). In patients with a clinical diagnosis of Costello syndrome, Zenker et al. (2007) identified mutations in the KRAS gene, but noted that these patients may later develop features of CFC syndrome. In either case, the findings underscore the central role of Ras in the pathogenesis of these phenotypically related disorders (Zenker et al., 2007). However, Kerr et al. (2008) commented that the diagnosis of Costello syndrome should only be used to refer to patients with mutations in the HRAS gene. (218040)

Disease Ontology : 12 A syndrome characterized by craniofacial dysmorphology, cardiac defects, mild mental retardation, and high birth weight followed by a failure to thrive and developmental delays.

Wikipedia : 72 Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare genetic disorder... more...

GeneReviews: NBK1507

Related Diseases for Costello Syndrome

Diseases related to Costello Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 84)
id Related Disease Score Top Affiliating Genes
1 cardiofaciocutaneous syndrome 11.3
2 cutis laxa, autosomal dominant 10.8
3 noonan syndrome 1 10.8
4 chaotic atrial tachycardia 10.8
5 sublingual gland adenoid cystic carcinoma 10.6 HRAS MAP2K1
6 nephrolithiasis 10.5 HRAS PTPN11
7 watson syndrome 10.5 MAP2K2 PTPN11
8 malignant skin fibrous histiocytoma 10.4 HRAS KRAS
9 limb ischemia 10.4 HRAS KRAS
10 severe pre-eclampsia 10.4 HRAS KRAS
11 schimmelpenning-feuerstein-mims syndrome, somatic mosaic 10.4 HRAS KRAS
12 gastric papillary adenocarcinoma 10.4 HRAS KRAS
13 adenocarcinoma in situ 10.4 HRAS KRAS
14 seminal vesicle chronic gonorrhea 10.4 HRAS KRAS
15 breast adenoid cystic carcinoma 10.4 HRAS KRAS
16 spindle epithelial tumor with thymus-like differentiation tumor 10.4 HRAS KRAS
17 tabes dorsalis 10.4 HRAS KRAS
18 rheumatic pulmonary valve disease 10.4 HRAS KRAS
19 appendix adenocarcinoma 10.3 HRAS KRAS
20 diffuse pulmonary fibrosis 10.3 HRAS KRAS
21 uterine corpus adenofibroma 10.3 HRAS KRAS
22 extramedullary plasmacytoma 10.3 HRAS KRAS
23 acinar cell cystadenocarcinoma 10.3 HRAS KRAS
24 c8 deficiency, type ii 10.3 MAP2K1 MAP2K2
25 migraine with aura 10.3 HRAS KRAS
26 hypersensitivity reaction type iii disease 10.3 HRAS KRAS
27 advanced sleep phase syndrome 10.3 HRAS KRAS
28 internal hordeolum 10.3 PTPN11 SOS1
29 gorham's disease 10.3 HRAS KRAS
30 progressive multifocal leukoencephalopathy 10.2 PTPN11 SOS1
31 dyserythropoietic anemia and thrombocytopenia 10.2 HRAS KRAS
32 cervical serous adenocarcinoma 10.2 PTPN11 SOS1
33 ossifying fibromyxoid tumor 10.2 HRAS KRAS
34 anuria 10.2 HRAS KRAS
35 peritoneal serous adenocarcinoma 10.1 HRAS KRAS
36 rhabdomyosarcoma 10.1
37 occupational dermatitis 10.1 HRAS KRAS MAP2K1
38 gastrointestinal neuroendocrine tumor 10.1 HRAS KRAS
39 lactocele 10.1 ELN HRAS
40 diencephalic astrocytomas 10.1 HRAS KRAS PTPN11
41 wolffian duct adenoma 10.0 HRAS KRAS
42 cardiomyopathy 10.0
43 embryonal rhabdomyosarcoma 10.0
44 cutis laxa 9.9
45 pancreatitis 9.9
46 hypoglycemia 9.9
47 early congenital syphilis 9.9 HRAS KRAS
48 hyperinsulinemic hypoglycemia 9.9
49 growth hormone deficiency 9.9
50 papilloma 9.8

Graphical network of the top 20 diseases related to Costello Syndrome:



Diseases related to Costello Syndrome

Symptoms & Phenotypes for Costello Syndrome

Symptoms via clinical synopsis from OMIM:

54

Growth- Height:
short stature
increased birth length

Head And Neck- Mouth:
high-arched palate
macroglossia
thick lips

Head And Neck- Nose:
anteverted nostrils
depressed nasal bridge

Head And Neck- Eyes:
strabismus
downslanting palpebral fissures
ptosis
epicanthal folds
hypertelorism

Skin Nails & Hair- Hair:
sparse hair
curly hair
thin anterior head hair

Prenatal Manifestations- Amniotic Fluid:
polyhydramnios

Chest- External Features:
pectus carinatum
barrel chest

Head And Neck- Head:
macrocephaly
large anterior fontanelle

Skeletal- Feet:
clubfeet
deep plantar creases

Respiratory- Airways:
tracheomalacia
bronchomalacia

Skeletal- Hands:
deep palmar creases
hyperextensible finger
wide distal phalanges
palmar nevi

Prenatal Manifestations- Delivery:
preterm delivery

Respiratory:
obstructive sleep apnea

Skin Nails & Hair- Nails:
brittle nails
thin, deep-set nails
koilonychia

Abdomen- Gastroin testinal:
poor suck in infancy
pyloric stenosis, hypertrophic

Growth- Other:
failure to thrive
fetal overgrowth
postnatal onset growth deficiency

Head And Neck- Face:
coarse facies
micrognathia
full cheeks
pointed chin

Neurologic- Central Nervous System:
delayed psychomotor development
mental retardation
ventriculomegaly
cerebral atrophy
hydrocephalus
more
Head And Neck- Ears:
low-set ears
posteriorly rotated ears
thickened lobes

Cardiovascular- Heart:
atrial septal defect
hypertrophic cardiomyopathy
arrhythmias
ventricular septal defect
pulmonic stenosis
more
Respiratory- Lung:
respiratory failure
lymphangiectasia
pneumothorax, recurrent
alveolar/capillary dysplasia
small lungs

Head And Neck- Neck:
short neck
webbed neck
loose, redundant neck skin

Laboratory- Abnormalities:
hypoglycemia

Genitourinary- Kidneys:
renal failure (in some patients)
dilated calyces (in some patients)
echogenic kidneys with thick-walled pelvises (in some patients)

Skin Nails & Hair- Skin:
deep palmar creases
acanthosis nigricans
palmar nevi
cutis laxa (especially hands and feet)
loose, redundant skin
more
Neoplasia:
rhabdomyosarcoma
epithelioma
bladder carcinoma
vestibular schwannoma

Growth- Weight:
increased birth weight

Voice:
hoarse voice

Head And Neck- Teeth:
defective enamel formation

Skeletal- Limbs:
restricted elbow motion
tight achilles tendon


Clinical features from OMIM:

218040

Human phenotypes related to Costello Syndrome:

56 32 (show top 50) (show all 97)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short stature 56 32 hallmark (90%) Very frequent (99-80%) HP:0004322
2 macroglossia 56 32 frequent (33%) Frequent (79-30%) HP:0000158
3 strabismus 56 32 frequent (33%) Frequent (79-30%) HP:0000486
4 depressed nasal bridge 56 32 hallmark (90%) Very frequent (99-80%) HP:0005280
5 coarse facial features 56 32 occasional (7.5%) Occasional (29-5%) HP:0000280
6 polyhydramnios 56 32 frequent (33%) Frequent (79-30%) HP:0001561
7 hypertrophic cardiomyopathy 56 32 frequent (33%) Frequent (79-30%) HP:0001639
8 narrow palate 56 32 hallmark (90%) Very frequent (99-80%) HP:0000189
9 hypoplastic toenails 56 32 frequent (33%) Frequent (79-30%) HP:0001800
10 gastroesophageal reflux 56 32 frequent (33%) Frequent (79-30%) HP:0002020
11 cryptorchidism 56 32 frequent (33%) Frequent (79-30%) HP:0000028
12 short neck 56 32 hallmark (90%) Very frequent (99-80%) HP:0000470
13 macrocephaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0000256
14 intellectual disability 56 32 frequent (33%) Frequent (79-30%) HP:0001249
15 keratoconus 56 32 frequent (33%) Frequent (79-30%) HP:0000563
16 ventricular septal defect 56 32 hallmark (90%) Very frequent (99-80%) HP:0001629
17 cerebral cortical atrophy 56 32 frequent (33%) Frequent (79-30%) HP:0002120
18 pulmonic stenosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0001642
19 hyperkeratosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0000962
20 full cheeks 56 32 frequent (33%) Frequent (79-30%) HP:0000293
21 low-set, posteriorly rotated ears 56 32 occasional (7.5%) Occasional (29-5%) HP:0000368
22 mitral valve prolapse 56 32 frequent (33%) Frequent (79-30%) HP:0001634
23 joint hyperflexibility 56 32 frequent (33%) Frequent (79-30%) HP:0005692
24 epicanthus 56 32 frequent (33%) Frequent (79-30%) HP:0000286
25 acanthosis nigricans 56 32 hallmark (90%) Very frequent (99-80%) HP:0000956
26 poor suck 56 32 occasional (7.5%) Occasional (29-5%) HP:0002033
27 delayed skeletal maturation 56 32 hallmark (90%) Very frequent (99-80%) HP:0002750
28 redundant skin 56 32 hallmark (90%) Very frequent (99-80%) HP:0001582
29 thickened achilles tendon 56 32 frequent (33%) Frequent (79-30%) HP:0004690
30 woolly hair 56 32 hallmark (90%) Very frequent (99-80%) HP:0002224
31 thick lower lip vermilion 56 32 frequent (33%) Frequent (79-30%) HP:0000179
32 failure to thrive in infancy 56 32 hallmark (90%) Very frequent (99-80%) HP:0001531
33 large face 56 32 occasional (7.5%) Occasional (29-5%) HP:0100729
34 deep-set nails 56 32 hallmark (90%) Very frequent (99-80%) HP:0001814
35 abnormal dermatoglyphics 56 32 frequent (33%) Frequent (79-30%) HP:0007477
36 lack of skin elasticity 56 32 hallmark (90%) Very frequent (99-80%) HP:0100679
37 thickened nuchal skin fold 56 32 frequent (33%) Frequent (79-30%) HP:0000474
38 abnormality of the fingernails 56 32 hallmark (90%) Very frequent (99-80%) HP:0001231
39 abnormality of dental enamel 56 32 frequent (33%) Frequent (79-30%) HP:0000682
40 ulnar deviation of finger 56 32 frequent (33%) Frequent (79-30%) HP:0009465
41 large earlobe 56 32 occasional (7.5%) Occasional (29-5%) HP:0009748
42 generalized hyperpigmentation 56 32 occasional (7.5%) Occasional (29-5%) HP:0007440
43 papilloma 56 32 frequent (33%) Frequent (79-30%) HP:0012740
44 concave nail 56 32 hallmark (90%) Very frequent (99-80%) HP:0001598
45 failure to thrive 32 HP:0001508
46 ventriculomegaly 32 HP:0002119
47 cerebral atrophy 32 HP:0002059
48 ptosis 32 HP:0000508
49 hydrocephalus 32 HP:0000238
50 low-set ears 32 HP:0000369

UMLS symptoms related to Costello Syndrome:


hoarseness, koilonychia

GenomeRNAi Phenotypes related to Costello Syndrome according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased cell migration GR00055-A-1 8.92 HRAS KRAS MAP2K2 SOS1

MGI Mouse Phenotypes related to Costello Syndrome:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10 HRAS KRAS MAP2K1 MAP2K2 MFAP2 PTPN11
2 craniofacial MP:0005382 9.98 CHST11 HRAS KRAS MAP2K1 MAP2K2 PTPN11
3 growth/size/body region MP:0005378 9.92 CHST11 HRAS KRAS MAP2K1 MAP2K2 MFAP2
4 endocrine/exocrine gland MP:0005379 9.85 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
5 digestive/alimentary MP:0005381 9.8 KRAS MAP2K1 MAP2K2 PTPN11 SOS1
6 integument MP:0010771 9.73 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
7 skeleton MP:0005390 9.56 CHST11 HRAS KRAS MAP2K1 MAP2K2 MFAP2
8 neoplasm MP:0002006 9.55 PTPN11 HRAS KRAS MAP2K1 MAP2K2
9 vision/eye MP:0005391 9.02 KRAS MAP2K1 MAP2K2 PTPN11 SOS1

Drugs & Therapeutics for Costello Syndrome

Drugs for Costello Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anesthetics

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Pathophysiology Analysis of "Costello Syndrome" on Cellular Models Completed NCT02812511

Search NIH Clinical Center for Costello Syndrome

Cochrane evidence based reviews: costello syndrome

Genetic Tests for Costello Syndrome

Genetic tests related to Costello Syndrome:

id Genetic test Affiliating Genes
1 Costello Syndrome 29 24 HRAS
2 Myopathy, Congenital, with Excess of Muscle Spindles 29

Anatomical Context for Costello Syndrome

MalaCards organs/tissues related to Costello Syndrome:

39
Skin, Heart, Brain, Lung, Kidney, Cerebellum, Pancreatic Islet

Publications for Costello Syndrome

Articles related to Costello Syndrome:

(show top 50) (show all 226)
id Title Authors Year
1
A novel patient with an attenuated Costello syndrome phenotype due to an HRAS mutation affecting codon 146-Literature review and update. ( 28328122 )
2017
2
Prenatal genetic diagnosis of Costello syndrome in a male fetus with recurrent HRAS mutation p.Gly12Ser. ( 28141901 )
2017
3
Cytotoxicity of Zardaverine in Embryonal Rhabdomyosarcoma from a Costello Syndrome Patient. ( 28421158 )
2017
4
Attenuated phenotype of Costello syndrome and early death in a patient with an HRAS mutation (c.179G>T; p.Gly60Val) affecting signalling dynamics. ( 28139825 )
2017
5
A comparison of the functional health of children with Costello syndrome in 1999 and in 2015. ( 28488342 )
2017
6
Age-related differences in prevalence of autism spectrum disorder symptoms in children and adolescents with Costello syndrome. ( 28374929 )
2017
7
Costello Syndrome and Umbilical Ligament Rhabdomyosarcoma in Two Pediatric Patients: Case Reports and Review of the Literature. ( 28203467 )
2017
8
Retinal dystrophy in two boys with Costello syndrome due to the HRAS p.Gly13Cys mutation. ( 28337834 )
2017
9
Mechanisms underlying cognitive deficits in a mouse model for Costello Syndrome are distinct from other RASopathy mouse models. ( 28455524 )
2017
10
Phenotypic spectrum of Costello syndrome individuals harboring the rare HRAS mutation p.Gly13Asp. ( 28371260 )
2017
11
Fetal costello syndrome with neuromuscular spindles excess and p.Gly12Val HRAS mutation. ( 28455154 )
2017
12
Understanding Growth Failure in Costello Syndrome: Increased Resting Energy Expenditure. ( 26778095 )
2016
13
Prenatal findings of hypertrophic cardiomyopathy in a severe case of Costello syndrome. ( 26916728 )
2016
14
The Splicing Efficiency of Activating HRAS Mutations Can Determine Costello Syndrome Phenotype and Frequency in Cancer. ( 27195699 )
2016
15
Palmoplantar Keratoderma in Costello Syndrome Responsive to Acitretin. ( 28008647 )
2016
16
Novel pathogenic variant in the HRAS gene with lethal outcome and a broad phenotypic spectrum among Polish patients with Costello syndrome. ( 28027064 )
2016
17
Human iPS Cell-Derived Neurons Uncover the Impact of Increased Ras Signaling in Costello Syndrome. ( 26740656 )
2016
18
Respiratory system involvement in Costello syndrome. ( 27102959 )
2016
19
Recombinant growth hormone therapy in a girl with Costello syndrome: a 4-year observation. ( 26812928 )
2016
20
Before and after - Nutritional transformation of dysmorphism in a case of Costello syndrome. ( 27705751 )
2016
21
EP05.10: Doppler assessment of hypertrophic cardiomyopathy in a case of Costello syndrome. ( 27647476 )
2016
22
Human papilloma virus-infected genital warts in a girl with Costello syndrome. ( 25787333 )
2015
23
Recurrent duplication mutation in HRAS causing mild Costello syndrome in a Chinese patient. ( 25677562 )
2015
24
Paternal uniparental disomy 11p15.5 in the pancreatic nodule of an infant with Costello syndrome: Shared mechanism for hyperinsulinemic hypoglycemia in neonates with Costello and Beckwith-Wiedemann syndrome and somatic loss of heterozygosity in Costello syndrome driving clonal expansion. ( 26572961 )
2015
25
Fatal congenital hypertrophic cardiomyopathy and a pancreatic nodule morphologically identical to focal lesion of congenital hyperinsulinism in an infant with Costello syndrome: Case report and review of the literature. ( 25668678 )
2015
26
An attenuated phenotype of Costello syndrome in three unrelated individuals with a HRAS c.179G>A (p.Gly60Asp) mutation correlates with uncommon functional consequences. ( 25914166 )
2015
27
Dysregulation of astrocyte extracellular signaling in Costello syndrome. ( 25947161 )
2015
28
Costello syndrome with severe nodulocystic acne: unexpected significant improvement of acanthosis nigricans after oral isotretinoin treatment. ( 25815234 )
2015
29
Costello syndrome: Analysis of the posterior cranial fossa in children with posterior fossa crowding. ( 26246091 )
2015
30
The role of p19 and p21 H-Ras proteins and mutants in miRNA expression in cancer and a Costello syndrome cell model. ( 26138095 )
2015
31
Anaesthetic Management in Costello Syndrome. ( 27366541 )
2015
32
In vivo synaptic transmission and morphology in mouse models of Tuberous sclerosis, Fragile X syndrome, Neurofibromatosis type 1, and Costello syndrome. ( 26190969 )
2015
33
Growth hormone replacement therapy in Costello syndrome. ( 25459872 )
2014
34
Perinatal features of the RASopathies: Noonan syndrome, Cardiofaciocutaneous syndrome and Costello syndrome. ( 25250515 )
2014
35
Early Postnatal Diagnosis of Costello Syndrome. ( 25062109 )
2014
36
Syndrome in question. Costello syndrome. ( 25387514 )
2014
37
Craniofacial and dental development in Costello syndrome. ( 24668879 )
2014
38
Decreased bone mineral density in Costello syndrome. ( 24246682 )
2014
39
Cardiac events in Costello syndrome: One case and a review of the literature. ( 24719541 )
2014
40
Abnormal Ras signaling in Costello syndrome (CS) negatively regulates enamel formation. ( 24057668 )
2014
41
Anesthetic management of Costello syndrome: a case report. ( 24902452 )
2014
42
Behavioral phenotype in Costello syndrome with atypical mutation: A case report. ( 25367099 )
2014
43
Early-Lethal Costello syndrome due to rare HRAS tandem base substitution (c.35_36GC>AA; p.G12E) associated pulmonary vascular disease. ( 25133308 )
2014
44
Uniparental Trisomy of a Mutated HRAS Proto-Oncogene in Embryonal Rhabdomyosarcoma of a Patient With Costello Syndrome. ( 24637993 )
2014
45
Function and disability in children with Costello syndrome and Cardiofaciocutaneous syndrome. ( 25346259 )
2014
46
Kinetic mechanisms of mutation-dependent Harvey Ras activation and their relevance for the development of Costello syndrome. ( 24224811 )
2013
47
Orthopedic manifestations and implications for individuals with Costello syndrome. ( 23813656 )
2013
48
Craniofacial and dental malformations in Costello syndrome: A detailed evaluation using multi-detector row computed tomography. ( 23751039 )
2013
49
'Cobblestone' papillomatous linear papules of the upper lip: a new sign of Costello syndrome. ( 23106483 )
2013
50
Verbal memory functioning in adolescents and young adults with Costello syndrome: evidence for relative preservation in recognition memory. ( 23918324 )
2013

Variations for Costello Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Costello Syndrome:

71 (show all 14)
id Symbol AA change Variation ID SNP ID
1 HRAS p.Gly12Val VAR_006836 rs104894230
2 HRAS p.Gly12Ser VAR_006837 rs104894229
3 HRAS p.Gly12Ala VAR_026106 rs104894230
4 HRAS p.Gly13Cys VAR_026107 rs104894228
5 HRAS p.Gly13Asp VAR_026108 rs104894226
6 HRAS p.Gly12Cys VAR_045975 rs104894229
7 HRAS p.Gly12Glu VAR_045976
8 HRAS p.Gln22Lys VAR_045977 rs121917757
9 HRAS p.Thr58Ile VAR_045978 rs121917758
10 HRAS p.Glu63Lys VAR_045980 rs121917756
11 HRAS p.Lys117Arg VAR_045981 rs104894227
12 HRAS p.Ala146Thr VAR_045982 rs104894231
13 HRAS p.Ala146Val VAR_045983 rs121917759
14 HRAS p.Gly12Asp VAR_068816 rs104894230

ClinVar genetic disease variations for Costello Syndrome:

6 (show all 19)
id Gene Variation Type Significance SNP ID Assembly Location
1 HRAS NM_005343.3(HRAS): c.35G> T (p.Gly12Val) single nucleotide variant Pathogenic/Likely pathogenic rs104894230 GRCh37 Chromosome 11, 534288: 534288
2 HRAS NM_005343.3(HRAS): c.34G> A (p.Gly12Ser) single nucleotide variant Pathogenic/Likely pathogenic rs104894229 GRCh37 Chromosome 11, 534289: 534289
3 HRAS NM_005343.3(HRAS): c.35G> C (p.Gly12Ala) single nucleotide variant Pathogenic/Likely pathogenic rs104894230 GRCh37 Chromosome 11, 534288: 534288
4 HRAS NM_005343.3(HRAS): c.38G> A (p.Gly13Asp) single nucleotide variant Pathogenic rs104894226 GRCh37 Chromosome 11, 534285: 534285
5 HRAS NM_005343.3(HRAS): c.350A> G (p.Lys117Arg) single nucleotide variant Pathogenic rs104894227 GRCh37 Chromosome 11, 533553: 533553
6 HRAS NM_005343.3(HRAS): c.187G> A (p.Glu63Lys) single nucleotide variant Pathogenic rs121917756 GRCh38 Chromosome 11, 533869: 533869
7 HRAS NM_005343.3(HRAS): c.64C> A (p.Gln22Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121917757 GRCh37 Chromosome 11, 534259: 534259
8 HRAS NM_176795.4(HRAS): c.173C> T (p.Thr58Ile) single nucleotide variant Pathogenic rs121917758 GRCh37 Chromosome 11, 533883: 533883
9 HRAS NM_005343.3(HRAS): c.37G> T (p.Gly13Cys) single nucleotide variant Pathogenic/Likely pathogenic rs104894228 GRCh37 Chromosome 11, 534286: 534286
10 HRAS NM_005343.3(HRAS): c.436G> A (p.Ala146Thr) single nucleotide variant Pathogenic/Likely pathogenic rs104894231 GRCh37 Chromosome 11, 533467: 533467
11 HRAS NM_005343.3(HRAS): c.437C> T (p.Ala146Val) single nucleotide variant Pathogenic/Likely pathogenic rs121917759 GRCh37 Chromosome 11, 533466: 533466
12 HRAS NM_005343.3(HRAS): c.35G> A (p.Gly12Asp) single nucleotide variant Pathogenic/Likely pathogenic rs104894230 GRCh37 Chromosome 11, 534288: 534288
13 HRAS NM_005343.3(HRAS): c.34G> T (p.Gly12Cys) single nucleotide variant Pathogenic/Likely pathogenic rs104894229 GRCh37 Chromosome 11, 534289: 534289
14 HRAS NM_005343.3(HRAS): c.110_111+1dupAGG duplication Pathogenic rs398122808 GRCh37 Chromosome 11, 534211: 534213
15 HRAS NM_005343.3(HRAS): c.108_110dupAGA (p.Glu37_Asp38insGlu) duplication Pathogenic rs398122809 GRCh37 Chromosome 11, 534213: 534215
16 HRAS NM_005343.3(HRAS): c.175G> A (p.Ala59Thr) single nucleotide variant Likely pathogenic rs727503093 GRCh37 Chromosome 11, 533881: 533881
17 HRAS NM_005343.3(HRAS): c.187_207dup21 (p.Asp69_Gln70insGluTyrSerAlaMetArgAsp) duplication Pathogenic rs587777239 GRCh38 Chromosome 11, 533849: 533869
18 HRAS NM_005343.3(HRAS): c.175_176delGCinsCT (p.Ala59Leu) indel Likely pathogenic rs727504747 GRCh38 Chromosome 11, 533880: 533881
19 HRAS NM_005343.3(HRAS): c.35_36delGCinsAA (p.Gly12Glu) indel Pathogenic/Likely pathogenic rs727503094 GRCh37 Chromosome 11, 534287: 534288

Copy number variations for Costello Syndrome from CNVD:

7
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 48338 11 1 2800000 Genomic rearrangemen t HRAS Costello syndrome

Expression for Costello Syndrome

Search GEO for disease gene expression data for Costello Syndrome.

Pathways for Costello Syndrome

Pathways related to Costello Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 165)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
13.67 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
2
Show member pathways
13.51 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
3
Show member pathways
13.48 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
4
Show member pathways
13.4 ELN HRAS KRAS MAP2K1 MAP2K2 SOS1
5
Show member pathways
13.37 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
6
Show member pathways
13.29 HRAS KRAS MAP2K1 MAP2K2 SOS1
7
Show member pathways
13.25 HRAS KRAS MAP2K1 MAP2K2 SOS1
8
Show member pathways
13.19 HRAS KRAS MAP2K1 MAP2K2 SOS1
9
Show member pathways
13.1 ELN HRAS KRAS MAP2K1 MAP2K2 SOS1
10
Show member pathways
13.06 HRAS KRAS MAP2K1 MAP2K2 SOS1
11
Show member pathways
13.03 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
12
Show member pathways
13.02 HRAS KRAS MAP2K1 MAP2K2 SOS1
13
Show member pathways
12.95 HRAS KRAS MAP2K1 MAP2K2 SOS1
14
Show member pathways
12.95 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
15
Show member pathways
12.94 HRAS KRAS MAP2K1 MAP2K2 SOS1
16
Show member pathways
12.93 HRAS KRAS MAP2K1 MAP2K2 SOS1
17
Show member pathways
12.92 HRAS KRAS MAP2K1 MAP2K2 SOS1
18
Show member pathways
12.91 HRAS KRAS MAP2K1 MAP2K2 SOS1
19
Show member pathways
12.9 HRAS KRAS MAP2K1 MAP2K2
20
Show member pathways
12.89 HRAS KRAS MAP2K1 SOS1
21
Show member pathways
12.88 HRAS KRAS MAP2K1 MAP2K2
22
Show member pathways
12.87 HRAS KRAS MAP2K1 SOS1
23
Show member pathways
12.86 HRAS KRAS MAP2K1 MAP2K2 SOS1
24
Show member pathways
12.85 HRAS KRAS PTPN11 SOS1
25
Show member pathways
12.83 HRAS KRAS MAP2K1 MAP2K2
26
Show member pathways
12.83 HRAS KRAS MAP2K1 MAP2K2 SOS1
27
Show member pathways
12.83 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
28
Show member pathways
12.82 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
29
Show member pathways
12.81 HRAS KRAS MAP2K1 MAP2K2
30 12.78 HRAS KRAS MAP2K1 MAP2K2 SOS1
31
Show member pathways
12.76 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
32
Show member pathways
12.74 HRAS KRAS PTPN11 SOS1
33 12.74 HRAS KRAS MAP2K1 MAP2K2 SOS1
34
Show member pathways
12.73 HRAS KRAS MAP2K1 MAP2K2 SOS1
35 12.71 HRAS KRAS MAP2K1 MAP2K2 SOS1
36 12.7 HRAS KRAS MAP2K1 MAP2K2 SOS1
37
Show member pathways
12.69 KRAS MAP2K1 MAP2K2 SOS1
38
Show member pathways
12.69 HRAS KRAS MAP2K1 MAP2K2
39
Show member pathways
12.66 HRAS MAP2K1 MAP2K2 SOS1
40
Show member pathways
12.65 HRAS MAP2K1 MAP2K2 SOS1
41
Show member pathways
12.63 HRAS MAP2K1 MAP2K2 SOS1
42
Show member pathways
12.63 HRAS MAP2K1 MAP2K2 PTPN11 SOS1
43
Show member pathways
12.62 HRAS KRAS PTPN11 SOS1
44
Show member pathways
12.61 HRAS KRAS PTPN11 SOS1
45
Show member pathways
12.61 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
46
Show member pathways
12.59 HRAS MAP2K1 MAP2K2 PTPN11 SOS1
47
Show member pathways
12.59 HRAS KRAS MAP2K1 MAP2K2 SOS1
48 12.58 HRAS KRAS MAP2K1 MAP2K2 SOS1
49
Show member pathways
12.57 HRAS KRAS MAP2K1 MAP2K2 SOS1
50
Show member pathways
12.55 HRAS KRAS MAP2K1 MAP2K2 SOS1

GO Terms for Costello Syndrome

Biological processes related to Costello Syndrome according to GeneCards Suite gene sharing:

(show all 24)
id Name GO ID Score Top Affiliating Genes
1 negative regulation of gene expression GO:0010629 9.78 HRAS MAP2K1 MAP2K2
2 Fc-epsilon receptor signaling pathway GO:0038095 9.77 HRAS KRAS SOS1
3 activation of MAPK activity GO:0000187 9.73 MAP2K1 MAP2K2 PTPN11
4 leukocyte migration GO:0050900 9.71 HRAS KRAS PTPN11 SOS1
5 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.67 HRAS MAP2K1 MAP2K2 PTPN11
6 Ras protein signal transduction GO:0007265 9.63 HRAS KRAS SOS1
7 respiratory gaseous exchange GO:0007585 9.62 CHST11 ELN
8 homeostasis of number of cells within a tissue GO:0048873 9.61 KRAS PTPN11
9 ERK1 and ERK2 cascade GO:0070371 9.6 MAP2K1 MAP2K2
10 cellular senescence GO:0090398 9.58 HRAS MAP2K1
11 regulation of long-term neuronal synaptic plasticity GO:0048169 9.58 HRAS KRAS
12 neurotrophin TRK receptor signaling pathway GO:0048011 9.57 PTPN11 SOS1
13 axon guidance GO:0007411 9.56 HRAS KRAS PTPN11 SOS1
14 response to isolation stress GO:0035900 9.55 HRAS KRAS
15 regulation of stress-activated MAPK cascade GO:0032872 9.54 MAP2K1 MAP2K2
16 Bergmann glial cell differentiation GO:0060020 9.52 MAP2K1 PTPN11
17 positive regulation of production of miRNAs involved in gene silencing by miRNA GO:1903800 9.51 MAP2K1 MAP2K2
18 regulation of early endosome to late endosome transport GO:2000641 9.49 MAP2K1 MAP2K2
19 proteolysis in other organism GO:0035897 9.48 MAP2K1 MAP2K2
20 regulation of Golgi inheritance GO:0090170 9.43 MAP2K1 MAP2K2
21 MAPK cascade GO:0000165 9.35 HRAS KRAS MAP2K1 MAP2K2 SOS1
22 ERBB2 signaling pathway GO:0038128 9.33 HRAS KRAS SOS1
23 cerebellar cortex formation GO:0021697 9.32 MAP2K1 PTPN11
24 epidermal growth factor receptor signaling pathway GO:0007173 8.92 HRAS KRAS PTPN11 SOS1

Molecular functions related to Costello Syndrome according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 protein serine/threonine/tyrosine kinase activity GO:0004712 9.26 MAP2K1 MAP2K2
2 protein serine/threonine kinase activator activity GO:0043539 9.16 MAP2K1 MAP2K2
3 MAP kinase kinase activity GO:0004708 8.96 MAP2K1 MAP2K2
4 nucleotide binding GO:0000166 8.92 HRAS KRAS MAP2K1 MAP2K2

Sources for Costello Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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