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CSTLO
MCID: CST001
MIFTS: 67
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Costello Syndrome (CSTLO)
Categories:
Cardiovascular diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases
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MalaCards integrated aliases for Costello Syndrome:
Characteristics:Orphanet epidemiological data:58
costello syndrome
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Japan); Age of onset: Antenatal,Neonatal; OMIM:56
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:31
costello syndrome:
Clinical modifier sudden death Inheritance autosomal dominant inheritance sporadic GeneReviews:24
Penetrance Penetrance is complete [aoki et al 2005, estep et al 2006, gripp et al 2006a, kerr et al 2006].
Classifications:
MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases Anatomical: Neuronal diseases Cardiovascular diseases Skin diseases
ICD10:
33
Orphanet: 58
Rare neurological diseases
Rare cardiac malformations
Rare skin diseases
Developmental anomalies during embryogenesis External Ids:
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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 with full lips. 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.
Beginning in early childhood, people with Costello syndrome are at an increased risk of developing certain cancerous and noncancerous tumors. The most common noncancerous tumors associated with this condition are papillomas, which are small, wart-like growths that usually develop around the nose and mouth or near the anus. The most common cancerous tumor associated with Costello syndrome is a childhood cancer called rhabdomyosarcoma, which begins in muscle tissue. Neuroblastoma, a tumor that arises in developing nerve cells, also has been reported in children and adolescents with this syndrome. In addition, some teenagers with Costello syndrome have developed transitional cell carcinoma, a form of bladder cancer that is usually seen in older adults.
The signs and symptoms of Costello syndrome overlap significantly with those of two other genetic conditions, cardiofaciocutaneous syndrome (CFC syndrome) and Noonan syndrome. In affected infants, it can be difficult to tell the three conditions apart based on their physical features. However, the conditions can be distinguished by their genetic cause and by specific patterns of signs and symptoms that develop later in childhood.
MalaCards based summary : Costello Syndrome, also known as faciocutaneoskeletal syndrome, is related to cardiofaciocutaneous syndrome 1 and cutis laxa, autosomal dominant 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 Innate Immune System. The drug Anesthetics has been mentioned in the context of this disorder. Affiliated tissues include skin, heart and brain, 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. NIH Rare Diseases : 52 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 . OMIM : 56 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) KEGG : 36 Costello syndrome (CS) is a rare multiple congenital abnormality syndrome. Patients present with the typical coarse face, deep palmar and plantar creases, redundant and loose skin, severe failure to thrive, congenital heart defect, and mild to severe mental retardation. Hyperpigmentation and papillomas can also be present. They have an increased risk of malignancy. The majority of patients show a mutation in HRAS. UniProtKB/Swiss-Prot : 73 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 : 74 Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare genetic disorder... more...
GeneReviews:
NBK1507
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Human phenotypes related to Costello Syndrome:58 31 (show top 50) (show all 100)
Symptoms via clinical synopsis from OMIM:56Clinical features from OMIM:218040UMLS symptoms related to Costello Syndrome:hoarseness, koilonychia GenomeRNAi Phenotypes related to Costello Syndrome according to GeneCards Suite gene sharing:26 (show all 13)
MGI Mouse Phenotypes related to Costello Syndrome:45 (show all 24)
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Drugs for Costello Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):
Interventional clinical trials:
Cochrane evidence based reviews: costello syndrome |
MalaCards organs/tissues related to Costello Syndrome:40
Skin,
Heart,
Brain,
Lung,
Bone,
Thyroid,
Myeloid
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Articles related to Costello Syndrome:(show top 50) (show all 425)
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Genes related to Costello Syndrome (1 elite genes):(show all 23) - Elite gene
- Cancer Census gene in COSMIC
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ClinVar genetic disease variations for Costello Syndrome:6 (show top 50) (show all 85)
UniProtKB/Swiss-Prot genetic disease variations for Costello Syndrome:73 (show all 14)
Copy number variations for Costello Syndrome from CNVD:7
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Search
GEO
for disease gene expression data for Costello Syndrome.
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Pathways related to Costello Syndrome according to KEGG:36
Pathways related to Costello Syndrome according to GeneCards Suite gene sharing:(show top 50) (show all 200)
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Cellular components related to Costello Syndrome according to GeneCards Suite gene sharing:
Biological processes related to Costello Syndrome according to GeneCards Suite gene sharing:(show all 50)
Molecular functions related to Costello Syndrome according to GeneCards Suite gene sharing:
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