Details of Disease | DrugMAP

General Information of Disease (ID: DISXVJH3)

Disease Name	Costello syndrome
Synonyms	CSTLO; myopathy, congenital, with excess of muscle spindles; congenital myopathy with excess of muscle spindles; Costello syndrome; faciocutaneoskeletal syndrome; FCS syndrome
Definition	Costello syndrome (CS) is a rare multisystemic disorder characterized by failure to thrive, short stature, developmental delay or intellectual disability, joint laxity, soft skin, and distinctive facial features. Cardiac and neurological involvement is common and there is an increased lifetime risk of certain tumors.
Disease Hierarchy	DISTATYK: Noonan syndrome and Noonan-related syndrome DIS3HIWD: Autosomal dominant disease DISDOXWZ: Multiple congenital anomalies/dysmorphic syndrome-intellectual disability DISXVJH3: Costello syndrome
Disease Identifiers	MONDO ID MONDO_0009026 MESH ID D056685 UMLS CUI C0587248 OMIM ID 218040 MedGen ID 108454 Orphanet ID 3071 SNOMED CT ID 309776008

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
MAP2K2	TT8H9GB	Limited	Genetic Variation	[1]
NRAS	TTW2R9X	Limited	Autosomal dominant	[2]
NRAS	TTW2R9X	Limited	Biomarker	[3]
RASA1	TTPNZ1F	Limited	Biomarker	[4]
BRAF	TT0EOB8	Disputed	Autosomal dominant	[2]
BRAF	TT0EOB8	Disputed	Genetic Variation	[1]
KRAS	TTRHMTC	Disputed	Autosomal dominant	[2]
KRAS	TTM8FR7	Disputed	Genetic Variation	[5]
MAP2K1	TTIDAPM	Disputed	Autosomal dominant	[2]
MAP2K1	TTIDAPM	Disputed	Genetic Variation	[1]
PTPN11	TT7WUAV	Disputed	Autosomal dominant	[2]
PTPN11	TT7WUAV	Disputed	Biomarker	[6]
RAF1	TTB18GJ	Disputed	Autosomal dominant	[2]
RAF1	TTAN5W2	Disputed	Genetic Variation	[7]
HRAS	TT28ZON	Definitive	Autosomal dominant	[2]
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⏷ Show the Full List of 15 DTT(s)

This Disease Is Related to 13 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
NRAS	OTVQ1DG3	Limited	Autosomal dominant	[2]
BRAF	OT7S81XQ	Disputed	Autosomal dominant	[2]
KRAS	OT78QCN8	Disputed	Autosomal dominant	[2]
MAP2K1	OT4Y9NQI	Disputed	Autosomal dominant	[2]
PTPN11	OTFH9M73	Disputed	Autosomal dominant	[2]
RAF1	OT51LSFO	Disputed	Autosomal dominant	[2]
SHOC2	OTUNQ2CT	Disputed	Autosomal dominant	[2]
SOS1	OTTCWXC3	Disputed	Autosomal dominant	[2]
CHST11	OTNJJ5Q1	Strong	Biomarker	[8]
ELN	OTFSO7PG	Strong	Posttranslational Modification	[9]
STATH	OTQHBHM9	Strong	Biomarker	[10]
TBCC	OTBF0X8R	Strong	Biomarker	[6]
HRAS	OTWQN0DP	Definitive	Autosomal dominant	[2]
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⏷ Show the Full List of 13 DOT(s)

References

1	Acute lymphoblastic leukemia in the context of RASopathies.Eur J Med Genet. 2016 Mar;59(3):173-8. doi: 10.1016/j.ejmg.2016.01.003. Epub 2016 Feb 5.
2	Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
3	Genotype and phenotype spectrum of NRAS germline variants.Eur J Hum Genet. 2017 Jun;25(7):823-831. doi: 10.1038/ejhg.2017.65. Epub 2017 May 3.
4	Duplication of Glu37 in the switch I region of HRAS impairs effector/GAP binding and underlies Costello syndrome by promoting enhanced growth factor-dependent MAPK and AKT activation.Hum Mol Genet. 2010 Mar 1;19(5):790-802. doi: 10.1093/hmg/ddp548. Epub 2009 Dec 8.
5	Concurrent somatic KRAS mutation and germline 10q22.3-q23.2 deletion in a patient with juvenile myelomonocytic leukemia, developmental delay, and multiple malformations: a case report.BMC Med Genomics. 2018 Jul 16;11(1):60. doi: 10.1186/s12920-018-0377-3.
6	Prenatal findings in cardio-facio-cutaneous syndrome.Am J Med Genet A. 2016 Feb;170A(2):441-445. doi: 10.1002/ajmg.a.37420. Epub 2015 Oct 22.
7	Spectrum of mutations in Noonan syndrome and their correlation with phenotypes.J Pediatr. 2011 Dec;159(6):1029-35. doi: 10.1016/j.jpeds.2011.05.024. Epub 2011 Jul 23.
8	C4ST-1/CHST11-controlled chondroitin sulfation interferes with oncogenic HRAS signaling in Costello syndrome.Eur J Hum Genet. 2012 Aug;20(8):870-7. doi: 10.1038/ejhg.2012.12. Epub 2012 Feb 8.
9	Retinoblastoma protein modulates the inverse relationship between cellular proliferation and elastogenesis. J Biol Chem. 2011 Oct 21;286(42):36580-91. doi: 10.1074/jbc.M111.269944. Epub 2011 Aug 31.
10	Paternal uniparental disomy with segmental loss of heterozygosity of chromosome 11 are hallmark characteristics of syndromic and sporadic embryonal rhabdomyosarcoma.Am J Med Genet A. 2016 Dec;170(12):3197-3206. doi: 10.1002/ajmg.a.37949. Epub 2016 Sep 2.