CMEMS
MCID: CST001
MIFTS: 64

Costello Syndrome (CMEMS)

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

Aliases & Classifications for Costello Syndrome

MalaCards integrated aliases for Costello Syndrome:

Name: Costello Syndrome 58 12 77 25 54 26 60 76 38 30 6 45 15 41 74
Faciocutaneoskeletal Syndrome 58 12 54 26 60 76
Fcs Syndrome 58 12 54 26 60 76
Myopathy, Congenital, with Excess of Muscle Spindles 30 6 74
Congenital Myopathy with Excess of Muscle Spindles 58 76 13
Cstlo 58 76
Cmems 76
Fcss 76

Characteristics:

Orphanet epidemiological data:

60
costello syndrome
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Japan); Age of onset: Antenatal,Neonatal;

OMIM:

58
Miscellaneous:
sudden death
de novo mutation in most cases
associated with advanced paternal age
characteristic facial features become more apparent with age
phenotypic overlap with noonan syndrome 3 or cardiofaciocutaneous syndrome

Inheritance:
autosomal dominant


HPO:

33
costello syndrome:
Clinical modifier sudden death
Inheritance autosomal dominant inheritance sporadic


GeneReviews:

25
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 : 54 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.

MalaCards based summary : Costello Syndrome, also known as faciocutaneoskeletal syndrome, is related to cardiofaciocutaneous syndrome 1 and noonan syndrome 1, and has symptoms including hoarseness and koilonychia. An important gene associated with Costello Syndrome is HRAS (HRas Proto-Oncogene, GTPase), and among its related pathways/superpathways are Ras signaling pathway and HIV Life Cycle. The drug Anesthetics has been mentioned in the context of this disorder. Affiliated tissues include skin, heart and lung, and related phenotypes are macrocephaly and short neck

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.

Genetics Home Reference : 26 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 : 58 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)

UniProtKB/Swiss-Prot : 76 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.

Wikipedia : 77 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 107)
# Related Disease Score Top Affiliating Genes
1 cardiofaciocutaneous syndrome 1 31.2 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
2 noonan syndrome 1 31.0 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
3 hypertrophic cardiomyopathy 29.9 KRAS PTPN11 SOS1
4 noonan syndrome 3 29.5 HRAS KRAS PTPN11 SOS1
5 cutis laxa, autosomal dominant 1 11.3
6 autosomal recessive cutis laxa type i 11.1
7 chaotic atrial tachycardia 11.1
8 rhabdomyosarcoma 10.3
9 ovarian melanoma 10.3 HRAS MAP2K1
10 myelodysplastic myeloproliferative cancer 10.3 HRAS PTPN11
11 neurofibromatosis-noonan syndrome 10.2 MAP2K2 PTPN11
12 leopard syndrome 10.2 HRAS PTPN11
13 sigmoid neoplasm 10.2 HRAS KRAS
14 apocrine adenoma 10.2 HRAS KRAS
15 periampullary adenoma 10.2 HRAS KRAS
16 paronychia 10.2 HRAS KRAS
17 schimmelpenning-feuerstein-mims syndrome 10.2 HRAS KRAS
18 bile duct cysts 10.2 HRAS KRAS
19 aggressive digital papillary adenocarcinoma 10.2 HRAS KRAS
20 appendix disease 10.2 HRAS KRAS
21 nevus, epidermal 10.2
22 embryonal rhabdomyosarcoma 10.2
23 hypoglycemia 10.2
24 lung adenoid cystic carcinoma 10.2 HRAS KRAS
25 nasal cavity adenocarcinoma 10.2 HRAS KRAS
26 secondary hypertrophic osteoarthropathy 10.2 HRAS KRAS
27 anal canal adenocarcinoma 10.2 HRAS KRAS
28 ovarian cystadenocarcinoma 10.2 HRAS KRAS
29 biliary papillomatosis 10.2 HRAS KRAS
30 colloid carcinoma of the pancreas 10.1 HRAS KRAS
31 bladder cancer 10.1
32 hyperinsulinemic hypoglycemia 10.1
33 cutis laxa 10.1
34 rosai-dorfman disease 10.1 KRAS MAP2K1
35 core binding factor acute myeloid leukemia 10.1 HRAS KRAS
36 mucinous lung adenocarcinoma 10.1 HRAS KRAS
37 villonodular synovitis 10.1 PTPN11 SOS1
38 duodenum cancer 10.1 HRAS KRAS
39 liver angiosarcoma 10.1 HRAS KRAS
40 cecum adenocarcinoma 10.1 HRAS KRAS
41 pulmonary valve stenosis 10.1 PTPN11 SOS1
42 pulmonary valve disease 10.1 PTPN11 SOS1
43 adenosquamous lung carcinoma 10.1 HRAS KRAS
44 growth hormone deficiency 10.1
45 pseudo-turner syndrome 10.1
46 ampulla of vater cancer 10.1 HRAS KRAS
47 gastrointestinal system benign neoplasm 10.1 HRAS KRAS
48 ovary adenocarcinoma 10.0 HRAS KRAS
49 skin squamous cell carcinoma 10.0 HRAS MAP2K2
50 bile duct adenocarcinoma 10.0 HRAS KRAS

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



Diseases related to Costello Syndrome

Symptoms & Phenotypes for Costello Syndrome

Human phenotypes related to Costello Syndrome:

60 33 (show top 50) (show all 100)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 60 33 hallmark (90%) Very frequent (99-80%) HP:0000256
2 short neck 60 33 hallmark (90%) Very frequent (99-80%) HP:0000470
3 narrow palate 60 33 hallmark (90%) Very frequent (99-80%) HP:0000189
4 delayed skeletal maturation 60 33 hallmark (90%) Very frequent (99-80%) HP:0002750
5 depressed nasal bridge 60 33 hallmark (90%) Very frequent (99-80%) HP:0005280
6 short stature 60 33 hallmark (90%) Very frequent (99-80%) HP:0004322
7 hyperkeratosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0000962
8 acanthosis nigricans 60 33 hallmark (90%) Very frequent (99-80%) HP:0000956
9 lack of skin elasticity 60 33 hallmark (90%) Very frequent (99-80%) HP:0100679
10 failure to thrive in infancy 60 33 hallmark (90%) Very frequent (99-80%) HP:0001531
11 ventricular septal defect 60 33 hallmark (90%) Very frequent (99-80%) HP:0001629
12 redundant skin 60 33 hallmark (90%) Very frequent (99-80%) HP:0001582
13 pulmonic stenosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0001642
14 woolly hair 60 33 hallmark (90%) Very frequent (99-80%) HP:0002224
15 concave nail 60 33 hallmark (90%) Very frequent (99-80%) HP:0001598
16 deep-set nails 60 33 hallmark (90%) Very frequent (99-80%) HP:0001814
17 abnormal fingernail morphology 33 hallmark (90%) HP:0001231
18 intellectual disability 60 33 frequent (33%) Frequent (79-30%) HP:0001249
19 macroglossia 60 33 frequent (33%) Frequent (79-30%) HP:0000158
20 gastroesophageal reflux 60 33 frequent (33%) Frequent (79-30%) HP:0002020
21 hypertrophic cardiomyopathy 60 33 frequent (33%) Frequent (79-30%) HP:0001639
22 full cheeks 60 33 frequent (33%) Frequent (79-30%) HP:0000293
23 thick lower lip vermilion 60 33 frequent (33%) Frequent (79-30%) HP:0000179
24 strabismus 60 33 frequent (33%) Frequent (79-30%) HP:0000486
25 joint hyperflexibility 60 33 frequent (33%) Frequent (79-30%) HP:0005692
26 epicanthus 60 33 frequent (33%) Frequent (79-30%) HP:0000286
27 cryptorchidism 60 33 frequent (33%) Frequent (79-30%) HP:0000028
28 thickened nuchal skin fold 60 33 frequent (33%) Frequent (79-30%) HP:0000474
29 hypoplastic toenails 60 33 frequent (33%) Frequent (79-30%) HP:0001800
30 abnormal dermatoglyphics 60 33 frequent (33%) Frequent (79-30%) HP:0007477
31 cerebral cortical atrophy 60 33 frequent (33%) Frequent (79-30%) HP:0002120
32 mitral valve prolapse 60 33 frequent (33%) Frequent (79-30%) HP:0001634
33 abnormality of dental enamel 60 33 frequent (33%) Frequent (79-30%) HP:0000682
34 polyhydramnios 60 33 frequent (33%) Frequent (79-30%) HP:0001561
35 ulnar deviation of finger 60 33 frequent (33%) Frequent (79-30%) HP:0009465
36 keratoconus 60 33 frequent (33%) Frequent (79-30%) HP:0000563
37 papilloma 60 33 frequent (33%) Frequent (79-30%) HP:0012740
38 thickened achilles tendon 60 33 frequent (33%) Frequent (79-30%) HP:0004690
39 large face 60 33 occasional (7.5%) Occasional (29-5%) HP:0100729
40 coarse facial features 60 33 occasional (7.5%) Occasional (29-5%) HP:0000280
41 low-set, posteriorly rotated ears 60 33 occasional (7.5%) Occasional (29-5%) HP:0000368
42 large earlobe 60 33 occasional (7.5%) Occasional (29-5%) HP:0009748
43 generalized hyperpigmentation 60 33 occasional (7.5%) Occasional (29-5%) HP:0007440
44 poor suck 60 33 occasional (7.5%) Occasional (29-5%) HP:0002033
45 renal insufficiency 33 occasional (7.5%) HP:0000083
46 hypertelorism 33 HP:0000316
47 low-set ears 33 HP:0000369
48 high palate 33 HP:0000218
49 hydrocephalus 33 HP:0000238
50 ptosis 33 HP:0000508

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Head:
macrocephaly
large anterior fontanel

Head And Neck Ears:
low-set ears
posteriorly rotated ears
thickened lobes

Neurologic Central Nervous System:
hydrocephalus
ventriculomegaly
cerebral atrophy
enlarged cerebellum
chiari i malformation
more
Head And Neck Mouth:
macroglossia
high-arched palate
thick lips

Chest External Features:
pectus carinatum
barrel chest

Cardiovascular Heart:
hypertrophic cardiomyopathy
atrial septal defect
mitral valve prolapse
ventricular septal defect
pulmonic stenosis
more
Laboratory Abnormalities:
hypoglycemia

Respiratory Lung:
respiratory failure
pneumothorax, recurrent
lymphangiectasia
alveolar/capillary dysplasia
small lungs

Voice:
hoarse voice

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

Neoplasia:
rhabdomyosarcoma
bladder carcinoma
vestibular schwannoma
epithelioma

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

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

Head And Neck Teeth:
defective enamel formation

Skeletal Limbs:
restricted elbow motion
tight achilles tendon

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

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

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

Head And Neck Nose:
depressed nasal bridge
anteverted nostrils

Growth Height:
short stature
increased birth length

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

Skin Nails Hair Skin:
acanthosis nigricans
deep palmar creases
palmar nevi
cutis laxa (especially hands and feet)
loose, redundant skin
more
Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Respiratory:
obstructive sleep apnea

Respiratory Airways:
tracheomalacia
bronchomalacia

Skeletal Feet:
deep plantar creases
clubfeet

Growth Weight:
increased birth weight

Prenatal Manifestations Delivery:
preterm delivery

Abdomen Gastrointestinal:
poor suck in infancy
pyloric stenosis, hypertrophic

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

Clinical features from OMIM:

218040

UMLS symptoms related to Costello Syndrome:


hoarseness, koilonychia

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

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased cell migration GR00055-A-1 9.26 HRAS KRAS MAP2K2 SOS1
2 Increased cell migration GR00055-A-3 8.8 HRAS KRAS SOS1

MGI Mouse Phenotypes related to Costello Syndrome:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.06 CHST11 HRAS KRAS MAP2K1 MAP2K2 MFAP2
2 craniofacial MP:0005382 9.98 CHST11 HRAS KRAS MAP2K1 MAP2K2 PTPN11
3 digestive/alimentary MP:0005381 9.95 CHST11 HRAS KRAS MAP2K1 MAP2K2 PTPN11
4 growth/size/body region MP:0005378 9.92 CHST11 HRAS KRAS MAP2K1 MAP2K2 MFAP2
5 endocrine/exocrine gland MP:0005379 9.91 CHST11 HRAS KRAS MAP2K1 MAP2K2 PTPN11
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 HRAS KRAS MAP2K1 MAP2K2 PTPN11
9 vision/eye MP:0005391 9.1 CHST11 KRAS MAP2K1 MAP2K2 PTPN11 SOS1

Drugs & Therapeutics for Costello Syndrome

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


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anesthetics Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Pathophysiology Analysis of "Costello Syndrome" on Cellular Models Completed NCT02812511 Not Applicable

Search NIH Clinical Center for Costello Syndrome

Cochrane evidence based reviews: costello syndrome

Genetic Tests for Costello Syndrome

Genetic tests related to Costello Syndrome:

# Genetic test Affiliating Genes
1 Costello Syndrome 30 HRAS
2 Myopathy, Congenital, with Excess of Muscle Spindles 30

Anatomical Context for Costello Syndrome

MalaCards organs/tissues related to Costello Syndrome:

42
Skin, Heart, Lung, Brain, Cerebellum, Kidney, Pancreas

Publications for Costello Syndrome

Articles related to Costello Syndrome:

(show top 50) (show all 244)
# Title Authors Year
1
Fetal edema, not overgrowth, is associated with neonatal lethal Costello syndrome due to the HRAS p.Gly12Val mutation. ( 30664540 )
2019
2
Anesthetic Management in an Adult Patient With Costello Syndrome: A Case Report. ( 30807300 )
2019
3
Fetal costello syndrome: a description of the phenotype of HRAS exon 1 mutations. ( 30937994 )
2019
4
Costello Syndrome: The Challenge of Hypoglycemia and Failure to Thrive. ( 29248509 )
2018
5
Age and ASD symptoms in Costello syndrome. ( 29575620 )
2018
6
Deep Palmar and Plantar Creases in Costello Syndrome. ( 29954608 )
2018
7
Age-related differences in prevalence of autism spectrum disorder symptoms in children and adolescents with Costello syndrome. ( 28374929 )
2017
8
Palmoplantar Keratoderma in Costello Syndrome Responsive to Acitretin. ( 28008647 )
2017
9
Novel pathogenic variant in the HRAS gene with lethal outcome and a broad phenotypic spectrum among Polish patients with Costello syndrome. ( 28027064 )
2017
10
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
11
Prenatal genetic diagnosis of Costello syndrome in a male fetus with recurrent HRAS mutation p.Gly12Ser. ( 28141901 )
2017
12
Costello Syndrome and Umbilical Ligament Rhabdomyosarcoma in Two Pediatric Patients: Case Reports and Review of the Literature. ( 28203467 )
2017
13
A novel patient with an attenuated Costello syndrome phenotype due to an HRAS mutation affecting codon 146-Literature review and update. ( 28328122 )
2017
14
Retinal dystrophy in two boys with Costello syndrome due to the HRAS p.Gly13Cys mutation. ( 28337834 )
2017
15
Phenotypic spectrum of Costello syndrome individuals harboring the rare HRAS mutation p.Gly13Asp. ( 28371260 )
2017
16
Cytotoxicity of Zardaverine in Embryonal Rhabdomyosarcoma from a Costello Syndrome Patient. ( 28421158 )
2017
17
Fetal costello syndrome with neuromuscular spindles excess and p.Gly12Val HRAS mutation. ( 28455154 )
2017
18
Mechanisms underlying cognitive deficits in a mouse model for Costello Syndrome are distinct from other RASopathy mouse models. ( 28455524 )
2017
19
A comparison of the functional health of children with Costello syndrome in 1999 and in 2015. ( 28488342 )
2017
20
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 )
2016
21
Human iPS Cell-Derived Neurons Uncover the Impact of Increased Ras Signaling in Costello Syndrome. ( 26740656 )
2016
22
Understanding Growth Failure in Costello Syndrome: Increased Resting Energy Expenditure. ( 26778095 )
2016
23
Recombinant growth hormone therapy in a girl with Costello syndrome: a 4-year observation. ( 26812928 )
2016
24
Prenatal findings of hypertrophic cardiomyopathy in a severe case of Costello syndrome. ( 26916728 )
2016
25
Respiratory system involvement in Costello syndrome. ( 27102959 )
2016
26
The Splicing Efficiency of Activating HRAS Mutations Can Determine Costello Syndrome Phenotype and Frequency in Cancer. ( 27195699 )
2016
27
Before and after - Nutritional transformation of dysmorphism in a case of Costello syndrome. ( 27705751 )
2016
28
Costello syndrome with severe nodulocystic acne: unexpected significant improvement of acanthosis nigricans after oral isotretinoin treatment. ( 25815234 )
2015
29
Uniparental Trisomy of a Mutated HRAS Proto-Oncogene in Embryonal Rhabdomyosarcoma of a Patient With Costello Syndrome. ( 24637993 )
2015
30
Early postnatal diagnosis of Costello syndrome. ( 25062109 )
2015
31
Function and disability in children with Costello syndrome and Cardiofaciocutaneous syndrome. ( 25346259 )
2015
32
Behavioral phenotype in Costello syndrome with atypical mutation: a case report. ( 25367099 )
2015
33
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
34
Recurrent duplication mutation in HRAS causing mild Costello syndrome in a Chinese patient. ( 25677562 )
2015
35
Human papilloma virus-infected genital warts in a girl with Costello syndrome. ( 25787333 )
2015
36
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
37
Dysregulation of astrocyte extracellular signaling in Costello syndrome. ( 25947161 )
2015
38
The role of p19 and p21 H-Ras proteins and mutants in miRNA expression in cancer and a Costello syndrome cell model. ( 26138095 )
2015
39
In vivo synaptic transmission and morphology in mouse models of Tuberous sclerosis, Fragile X syndrome, Neurofibromatosis type 1, and Costello syndrome. ( 26190969 )
2015
40
Costello syndrome: Analysis of the posterior cranial fossa in children with posterior fossa crowding. ( 26246091 )
2015
41
Anaesthetic Management in Costello Syndrome. ( 27366541 )
2015
42
Abnormal Ras signaling in Costello syndrome (CS) negatively regulates enamel formation. ( 24057668 )
2014
43
HRAS mutations in bladder cancer at an early age and the possible association with the Costello Syndrome. ( 24169525 )
2014
44
Decreased bone mineral density in Costello syndrome. ( 24246682 )
2014
45
Craniofacial and dental development in Costello syndrome. ( 24668879 )
2014
46
Cardiac events in Costello syndrome: One case and a review of the literature. ( 24719541 )
2014
47
Anesthetic management of Costello syndrome: a case report. ( 24902452 )
2014
48
Early-lethal Costello syndrome due to rare HRAS Tandem Base substitution (c.35_36GC>AA; p.G12E)-associated pulmonary vascular disease. ( 25133308 )
2014
49
Perinatal features of the RASopathies: Noonan syndrome, cardiofaciocutaneous syndrome and Costello syndrome. ( 25250515 )
2014
50
Syndrome in question. Costello syndrome. ( 25387514 )
2014

Variations for Costello Syndrome

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

76 (show all 14)
# 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 top 50) (show all 208)
# Gene Variation Type Significance SNP ID Assembly Location
1 TNNT2 NM_000364.3(TNNT2): c.853C> T (p.Arg285Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs121964857 GRCh37 Chromosome 1, 201328373: 201328373
2 TNNT2 NM_000364.3(TNNT2): c.853C> T (p.Arg285Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs121964857 GRCh38 Chromosome 1, 201359245: 201359245
3 HRAS NM_005343.2(HRAS): c.35G> T (p.Gly12Val) single nucleotide variant Pathogenic rs104894230 GRCh37 Chromosome 11, 534288: 534288
4 HRAS NM_005343.2(HRAS): c.35G> T (p.Gly12Val) single nucleotide variant Pathogenic rs104894230 GRCh38 Chromosome 11, 534288: 534288
5 HRAS NM_176795.4(HRAS): c.34G> A (p.Gly12Ser) single nucleotide variant Pathogenic rs104894229 GRCh37 Chromosome 11, 534289: 534289
6 HRAS NM_176795.4(HRAS): c.34G> A (p.Gly12Ser) single nucleotide variant Pathogenic rs104894229 GRCh38 Chromosome 11, 534289: 534289
7 HRAS NM_005343.3(HRAS): c.437C> T (p.Ala146Val) single nucleotide variant Likely pathogenic rs121917759 GRCh38 Chromosome 11, 533466: 533466
8 HRAS NM_005343.2(HRAS): c.35G> A (p.Gly12Asp) single nucleotide variant Pathogenic rs104894230 GRCh37 Chromosome 11, 534288: 534288
9 HRAS NM_005343.2(HRAS): c.35G> A (p.Gly12Asp) single nucleotide variant Pathogenic rs104894230 GRCh38 Chromosome 11, 534288: 534288
10 HRAS NM_005343.2(HRAS): c.35G> C (p.Gly12Ala) single nucleotide variant Pathogenic rs104894230 GRCh37 Chromosome 11, 534288: 534288
11 HRAS NM_005343.2(HRAS): c.64C> A (p.Gln22Lys) single nucleotide variant Likely pathogenic rs121917757 GRCh37 Chromosome 11, 534259: 534259
12 HRAS NM_005343.2(HRAS): c.64C> A (p.Gln22Lys) single nucleotide variant Likely pathogenic rs121917757 GRCh38 Chromosome 11, 534259: 534259
13 HRAS NM_176795.4(HRAS): c.173C> T (p.Thr58Ile) single nucleotide variant Pathogenic rs121917758 GRCh37 Chromosome 11, 533883: 533883
14 HRAS NM_176795.4(HRAS): c.173C> T (p.Thr58Ile) single nucleotide variant Pathogenic rs121917758 GRCh38 Chromosome 11, 533883: 533883
15 HRAS NM_005343.3(HRAS): c.437C> T (p.Ala146Val) single nucleotide variant Likely pathogenic rs121917759 GRCh37 Chromosome 11, 533466: 533466
16 HRAS NM_005343.2(HRAS): c.35G> C (p.Gly12Ala) single nucleotide variant Pathogenic rs104894230 GRCh38 Chromosome 11, 534288: 534288
17 HRAS NM_005343.2(HRAS): c.38G> A (p.Gly13Asp) single nucleotide variant Pathogenic rs104894226 GRCh37 Chromosome 11, 534285: 534285
18 HRAS NM_005343.2(HRAS): c.38G> A (p.Gly13Asp) single nucleotide variant Pathogenic rs104894226 GRCh38 Chromosome 11, 534285: 534285
19 HRAS NM_005343.4(HRAS): c.350A> G (p.Lys117Arg) single nucleotide variant Pathogenic rs104894227 GRCh37 Chromosome 11, 533553: 533553
20 HRAS NM_005343.4(HRAS): c.350A> G (p.Lys117Arg) single nucleotide variant Pathogenic rs104894227 GRCh38 Chromosome 11, 533553: 533553
21 HRAS NM_005343.4(HRAS): c.37G> T (p.Gly13Cys) single nucleotide variant Pathogenic rs104894228 GRCh37 Chromosome 11, 534286: 534286
22 HRAS NM_005343.4(HRAS): c.37G> T (p.Gly13Cys) single nucleotide variant Pathogenic rs104894228 GRCh38 Chromosome 11, 534286: 534286
23 HRAS NM_005343.3(HRAS): c.436G> A (p.Ala146Thr) single nucleotide variant Pathogenic/Likely pathogenic rs104894231 GRCh37 Chromosome 11, 533467: 533467
24 HRAS NM_005343.3(HRAS): c.436G> A (p.Ala146Thr) single nucleotide variant Pathogenic/Likely pathogenic rs104894231 GRCh38 Chromosome 11, 533467: 533467
25 HRAS NM_005343.2(HRAS): c.187G> A (p.Glu63Lys) single nucleotide variant Pathogenic rs121917756 GRCh37 Chromosome 11, 533869: 533869
26 HRAS NM_005343.2(HRAS): c.187G> A (p.Glu63Lys) single nucleotide variant Pathogenic rs121917756 GRCh38 Chromosome 11, 533869: 533869
27 HRAS NM_005343.2(HRAS): c.34G> T (p.Gly12Cys) single nucleotide variant Pathogenic rs104894229 GRCh37 Chromosome 11, 534289: 534289
28 HRAS NM_005343.2(HRAS): c.34G> T (p.Gly12Cys) single nucleotide variant Pathogenic rs104894229 GRCh38 Chromosome 11, 534289: 534289
29 HRAS NM_005343.3(HRAS): c.110_111+1dup duplication Pathogenic rs398122808 GRCh37 Chromosome 11, 534211: 534213
30 HRAS NM_005343.3(HRAS): c.110_111+1dup duplication Pathogenic rs398122808 GRCh38 Chromosome 11, 534211: 534213
31 HRAS NM_005343.3(HRAS): c.108_110dup (p.Glu37_Asp38insGlu) duplication Pathogenic rs398122809 GRCh37 Chromosome 11, 534213: 534215
32 HRAS NM_005343.3(HRAS): c.108_110dup (p.Glu37_Asp38insGlu) duplication Pathogenic rs398122809 GRCh38 Chromosome 11, 534213: 534215
33 HRAS NM_005343.4(HRAS): c.81T> C (p.His27=) single nucleotide variant Benign rs12628 GRCh37 Chromosome 11, 534242: 534242
34 HRAS NM_005343.4(HRAS): c.81T> C (p.His27=) single nucleotide variant Benign rs12628 GRCh38 Chromosome 11, 534242: 534242
35 HRAS NM_005343.4(HRAS): c.175G> A (p.Ala59Thr) single nucleotide variant Likely pathogenic rs727503093 GRCh37 Chromosome 11, 533881: 533881
36 HRAS NM_005343.4(HRAS): c.175G> A (p.Ala59Thr) single nucleotide variant Likely pathogenic rs727503093 GRCh38 Chromosome 11, 533881: 533881
37 HRAS NM_005343.4(HRAS): c.257A> C (p.Asn86Thr) single nucleotide variant Benign rs138272051 GRCh37 Chromosome 11, 533799: 533799
38 HRAS NM_005343.4(HRAS): c.257A> C (p.Asn86Thr) single nucleotide variant Benign rs138272051 GRCh38 Chromosome 11, 533799: 533799
39 HRAS NM_176795.4(HRAS): c.277A> G (p.Ile93Val) single nucleotide variant Uncertain significance rs587782949 GRCh37 Chromosome 11, 533779: 533779
40 HRAS NM_176795.4(HRAS): c.277A> G (p.Ile93Val) single nucleotide variant Uncertain significance rs587782949 GRCh38 Chromosome 11, 533779: 533779
41 HRAS NM_005343.4(HRAS): c.309G> A (p.Val103=) single nucleotide variant Benign rs575789207 GRCh37 Chromosome 11, 533594: 533594
42 HRAS NM_005343.4(HRAS): c.309G> A (p.Val103=) single nucleotide variant Benign rs575789207 GRCh38 Chromosome 11, 533594: 533594
43 HRAS NM_005343.4(HRAS): c.357C> T (p.Asp119=) single nucleotide variant Benign rs111352454 GRCh37 Chromosome 11, 533546: 533546
44 HRAS NM_005343.4(HRAS): c.357C> T (p.Asp119=) single nucleotide variant Benign rs111352454 GRCh38 Chromosome 11, 533546: 533546
45 HRAS NM_005343.4(HRAS): c.378A> G (p.Glu126=) single nucleotide variant Benign rs397517140 GRCh37 Chromosome 11, 533525: 533525
46 HRAS NM_005343.4(HRAS): c.378A> G (p.Glu126=) single nucleotide variant Benign rs397517140 GRCh38 Chromosome 11, 533525: 533525
47 HRAS NM_005343.2(HRAS): c.460G> A (p.Asp154Asn) single nucleotide variant Uncertain significance rs745497215 GRCh37 Chromosome 11, 532746: 532746
48 HRAS NM_005343.2(HRAS): c.460G> A (p.Asp154Asn) single nucleotide variant Uncertain significance rs745497215 GRCh38 Chromosome 11, 532746: 532746
49 HRAS NM_005343.4(HRAS): c.477G> A (p.Leu159=) single nucleotide variant Benign rs140060409 GRCh37 Chromosome 11, 532729: 532729
50 HRAS NM_005343.4(HRAS): c.477G> A (p.Leu159=) single nucleotide variant Benign rs140060409 GRCh38 Chromosome 11, 532729: 532729

Copy number variations for Costello Syndrome from CNVD:

7
# 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 KEGG:

38
# Name Kegg Source Accession
1 Ras signaling pathway hsa04014

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

(show top 50) (show all 180)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.67 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
2
Show member pathways
13.52 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
3
Show member pathways
13.49 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
4
Show member pathways
13.41 ELN HRAS KRAS MAP2K1 MAP2K2 SOS1
5
Show member pathways
13.37 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
6
Show member pathways
13.3 HRAS KRAS MAP2K1 MAP2K2 SOS1
7
Show member pathways
13.26 HRAS KRAS MAP2K1 MAP2K2 SOS1
8
Show member pathways
13.2 HRAS KRAS MAP2K1 MAP2K2 SOS1
9
Show member pathways
13.11 ELN HRAS KRAS MAP2K1 MAP2K2 SOS1
10
Show member pathways
13.08 HRAS KRAS MAP2K1 MAP2K2 SOS1
11
Show member pathways
13.06 HRAS KRAS MAP2K1 MAP2K2 SOS1
12
Show member pathways
13.06 HRAS KRAS MAP2K1 MAP2K2 SOS1
13
Show member pathways
13.04 HRAS KRAS MAP2K1 MAP2K2 SOS1
14
Show member pathways
13.02 HRAS KRAS MAP2K1 MAP2K2 SOS1
15
Show member pathways
12.99 HRAS KRAS MAP2K1 MAP2K2 SOS1
16
Show member pathways
12.98 HRAS KRAS MAP2K1 MAP2K2 SOS1
17
Show member pathways
12.96 HRAS KRAS MAP2K1 MAP2K2 SOS1
18
Show member pathways
12.96 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
19
Show member pathways
12.95 HRAS KRAS MAP2K1 MAP2K2 SOS1
20
Show member pathways
12.95 HRAS KRAS MAP2K1 MAP2K2 SOS1
21
Show member pathways
12.92 HRAS KRAS MAP2K1 MAP2K2 SOS1
22
Show member pathways
12.92 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
23
Show member pathways
12.91 HRAS KRAS MAP2K1 MAP2K2
24 12.9 HRAS KRAS MAP2K1 MAP2K2 SOS1
25
Show member pathways
12.88 HRAS KRAS MAP2K1 SOS1
26
Show member pathways
12.87 HRAS KRAS MAP2K1 MAP2K2 SOS1
27
Show member pathways
12.86 HRAS MAP2K1 MAP2K2 SOS1
28
Show member pathways
12.86 HRAS KRAS PTPN11 SOS1
29
Show member pathways
12.84 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
30
Show member pathways
12.83 HRAS KRAS MAP2K1 MAP2K2
31 12.83 HRAS KRAS MAP2K1 MAP2K2 SOS1
32
Show member pathways
12.83 HRAS KRAS MAP2K1 MAP2K2 SOS1
33
Show member pathways
12.82 HRAS KRAS MAP2K1 MAP2K2
34
Show member pathways
12.79 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
35
Show member pathways
12.78 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
36
Show member pathways
12.77 HRAS KRAS MAP2K1 MAP2K2
37
Show member pathways
12.76 HRAS KRAS MAP2K1 MAP2K2 SOS1
38
Show member pathways
12.75 HRAS KRAS PTPN11 SOS1
39
Show member pathways
12.74 HRAS KRAS MAP2K1 MAP2K2 SOS1
40
Show member pathways
12.74 HRAS KRAS MAP2K1 MAP2K2 SOS1
41
Show member pathways
12.71 HRAS KRAS MAP2K1 MAP2K2
42 12.71 HRAS KRAS MAP2K1 MAP2K2 SOS1
43
Show member pathways
12.7 KRAS MAP2K1 MAP2K2 SOS1
44
Show member pathways
12.66 HRAS MAP2K1 MAP2K2 SOS1
45
Show member pathways
12.66 HRAS MAP2K1 MAP2K2 SOS1
46
Show member pathways
12.65 HRAS MAP2K1 MAP2K2 PTPN11 SOS1
47
Show member pathways
12.65 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1
48
Show member pathways
12.64 HRAS MAP2K1 MAP2K2 SOS1
49
Show member pathways
12.63 HRAS KRAS PTPN11 SOS1
50
Show member pathways
12.62 HRAS KRAS MAP2K1 MAP2K2 PTPN11 SOS1

GO Terms for Costello Syndrome

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

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of gene expression GO:0010629 9.75 HRAS MAP2K1 MAP2K2
2 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.73 HRAS MAP2K1 PTPN11
3 activation of MAPK activity GO:0000187 9.65 MAP2K1 MAP2K2 PTPN11
4 respiratory gaseous exchange GO:0007585 9.57 CHST11 ELN
5 homeostasis of number of cells within a tissue GO:0048873 9.55 KRAS PTPN11
6 ERK1 and ERK2 cascade GO:0070371 9.54 MAP2K1 MAP2K2
7 cellular senescence GO:0090398 9.52 HRAS MAP2K1
8 regulation of long-term neuronal synaptic plasticity GO:0048169 9.51 HRAS KRAS
9 neurotrophin TRK receptor signaling pathway GO:0048011 9.49 PTPN11 SOS1
10 positive regulation of production of miRNAs involved in gene silencing by miRNA GO:1903800 9.46 MAP2K1 MAP2K2
11 regulation of stress-activated MAPK cascade GO:0032872 9.43 MAP2K1 MAP2K2
12 Ras protein signal transduction GO:0007265 9.43 HRAS KRAS SOS1
13 Bergmann glial cell differentiation GO:0060020 9.4 MAP2K1 PTPN11
14 regulation of early endosome to late endosome transport GO:2000641 9.37 MAP2K1 MAP2K2
15 response to isolation stress GO:0035900 9.32 HRAS KRAS
16 regulation of Golgi inheritance GO:0090170 9.16 MAP2K1 MAP2K2
17 MAPK cascade GO:0000165 9.02 HRAS KRAS MAP2K1 MAP2K2 SOS1
18 cerebellar cortex formation GO:0021697 8.96 MAP2K1 PTPN11

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

# Name GO ID Score Top Affiliating Genes
1 protein serine/threonine kinase activator activity GO:0043539 9.26 MAP2K1 MAP2K2
2 protein serine/threonine/tyrosine kinase activity GO:0004712 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
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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