Costello Syndrome (CMEMS)

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Disease Ontology 12 DOID:0050469 OMIM 58 218040 KEGG 38 H01747 MeSH 45 D056685 NCIt 51 C84652 MESH via Orphanet 46 D056685

ICD10 via Orphanet 35 Q87.8 UMLS via Orphanet 75 C0587248 Orphanet 60 ORPHA3071 MedGen 43 C0587248 C1968782 SNOMED-CT via HPO 70 102594003 11731003 11934000 123983008 126949007 128602000 16331000 194021007 201093004 203076007 204878001 205101001 21119008 22006008 22066006 224958001 225570000 228156007 230745008 233873004 235595009 236423003 23730008 237630007 237836003 24228002 246800008 247578003 249808002 25273001 253185002 253251006 253366007 253549006 255108000 263681008 26636000 26996000 271327008 27272007 276662009 278849000 282020008 297957009 302847003 302866003 30288003 30924005 32958008 36118008 36440009 367403001 367494004 367510009 396228006 397932003 399955009 400096001 402599005 405752007 409622000 409623005 409712001 418143002 42399005 432788009 44808001 45227007 4830009 49550006 49765009 50219008 51697005 52522001 52564001 54203008 56786000 63829008 65636009 66270006 66865009 698065002 698247007 70142008 708670007 711329002 72129000 78275009 8074002 83145004 86203003 91138005 95427009 95434006 95515009 985004 more UMLS 74 C0587248 C1968782

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

Clinical features from OMIM:

218040

#	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

Search NIH Clinical Center for Costello Syndrome

Search GEO for disease gene expression data for Costello Syndrome.