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RASopathy

MedGen UID:
1792298
Concept ID:
C5555857
Disease or Syndrome
Synonyms: Noonan spectrum disorder; rasopathies
 
Related genes: SPRED1, ARHGAP26, LZTR1, SHOC2, SOS1, RIT1, RAF1, PTPN11, MAP2K1, NRAS, NF1, KRAS, HRAS, CBL, BRAF
 
Monarch Initiative: MONDO:0021060
Orphanet: ORPHA536391

Definition

A group of genetic disorders associated with mutation(s) in genes that are constituents of the RAS signaling pathway. These disorders are characterized by distinct facial features, developmental delays, cardiac defects, growth delays, and feeding problems. Representative examples include: neurofibromatosis type 1, capillary malformation-arteriovenous malformation syndrome, cardiofaciocutaneous syndrome, Costello syndrome, multiple lentigines syndrome, and Noonan syndrome. [from NCI]

Professional guidelines

PubMed

Linglart L, Gelb BD
Am J Med Genet C Semin Med Genet 2020 Mar;184(1):73-80. Epub 2020 Feb 5 doi: 10.1002/ajmg.c.31765. PMID: 32022400Free PMC Article
Ly KI, Blakeley JO
Med Clin North Am 2019 Nov;103(6):1035-1054. doi: 10.1016/j.mcna.2019.07.004. PMID: 31582003
Gripp KW, Morse LA, Axelrad M, Chatfield KC, Chidekel A, Dobyns W, Doyle D, Kerr B, Lin AE, Schwartz DD, Sibbles BJ, Siegel D, Shankar SP, Stevenson DA, Thacker MM, Weaver KN, White SM, Rauen KA
Am J Med Genet A 2019 Sep;179(9):1725-1744. Epub 2019 Jun 20 doi: 10.1002/ajmg.a.61270. PMID: 31222966Free PMC Article

Recent clinical studies

Etiology

Zenker M
Am J Med Genet C Semin Med Genet 2022 Dec;190(4):414-424. Epub 2022 Nov 25 doi: 10.1002/ajmg.c.32015. PMID: 36428239
Hebron KE, Hernandez ER, Yohe ME
Dis Model Mech 2022 Feb 1;15(2) Epub 2022 Feb 18 doi: 10.1242/dmm.049107. PMID: 35178568Free PMC Article
Rauen KA
Dis Model Mech 2022 Feb 1;15(2) doi: 10.1242/dmm.049344. PMID: 35103797Free PMC Article
Hathaway J, Heliö K, Saarinen I, Tallila J, Seppälä EH, Tuupanen S, Turpeinen H, Kangas-Kontio T, Schleit J, Tommiska J, Kytölä V, Valori M, Muona M, Sistonen J, Gentile M, Salmenperä P, Myllykangas S, Paananen J, Alastalo TP, Heliö T, Koskenvuo J
BMC Cardiovasc Disord 2021 Mar 5;21(1):126. doi: 10.1186/s12872-021-01927-5. PMID: 33673806Free PMC Article
Gelb BD, Cavé H, Dillon MW, Gripp KW, Lee JA, Mason-Suares H, Rauen KA, Williams B, Zenker M, Vincent LM; ClinGen RASopathy Working Group
Genet Med 2018 Nov;20(11):1334-1345. Epub 2018 Mar 1 doi: 10.1038/gim.2018.3. PMID: 29493581Free PMC Article

Diagnosis

Delogu AB, Limongelli G, Versacci P, Adorisio R, Kaski JP, Blandino R, Maiolo S, Monda E, Putotto C, De Rosa G, Chatfield KC, Gelb BD, Calcagni G
Am J Med Genet C Semin Med Genet 2022 Dec;190(4):440-451. Epub 2022 Nov 21 doi: 10.1002/ajmg.c.32014. PMID: 36408797
Lioncino M, Monda E, Verrillo F, Moscarella E, Calcagni G, Drago F, Marino B, Digilio MC, Putotto C, Calabrò P, Russo MG, Roberts AE, Gelb BD, Tartaglia M, Limongelli G
Heart Fail Clin 2022 Jan;18(1):19-29. Epub 2021 Oct 25 doi: 10.1016/j.hfc.2021.07.004. PMID: 34776080Free PMC Article
Patnaik MM, Lasho TL
Hematology Am Soc Hematol Educ Program 2020 Dec 4;2020(1):450-459. doi: 10.1182/hematology.2020000130. PMID: 33275756Free PMC Article
Linglart L, Gelb BD
Am J Med Genet C Semin Med Genet 2020 Mar;184(1):73-80. Epub 2020 Feb 5 doi: 10.1002/ajmg.c.31765. PMID: 32022400Free PMC Article
Ly KI, Blakeley JO
Med Clin North Am 2019 Nov;103(6):1035-1054. doi: 10.1016/j.mcna.2019.07.004. PMID: 31582003

Therapy

Lynch A, Tatangelo M, Ahuja S, Steve Fan CP, Min S, Lafreniere-Roula M, Papaz T, Zhou V, Armstrong K, Aziz PF, Benson LN, Butts R, Dragulescu A, Gardin L, Godown J, Jeewa A, Kantor PF, Kaufman BD, Lal AK, Parent JJ, Richmond M, Russell MW, Balaji S, Stephenson EA, Villa C, Jefferies JL, Whitehill R, Conway J, Howard TS, Nakano SJ, Rossano J, Weintraub RG, Mital S
J Am Coll Cardiol 2023 Mar 21;81(11):1035-1045. doi: 10.1016/j.jacc.2023.01.012. PMID: 36922089
Han Y, Chen M, Wang H
Childs Nerv Syst 2021 Jun;37(6):1831-1836. Epub 2021 Jan 6 doi: 10.1007/s00381-020-05034-2. PMID: 33409618
Bergqvist C, Wolkenstein P
Curr Opin Oncol 2021 Mar 1;33(2):110-119. doi: 10.1097/CCO.0000000000000711. PMID: 33395032
Staedtke V, Bai RY, Blakeley JO
Neurotherapeutics 2017 Apr;14(2):298-306. doi: 10.1007/s13311-017-0518-y. PMID: 28349408Free PMC Article
Lim YH, Ovejero D, Derrick KM; Yale Center for Mendelian Genomics, Collins MT, Choate KA
J Am Acad Dermatol 2016 Aug;75(2):420-7. doi: 10.1016/j.jaad.2015.11.012. PMID: 27444071Free PMC Article

Prognosis

Delogu AB, Limongelli G, Versacci P, Adorisio R, Kaski JP, Blandino R, Maiolo S, Monda E, Putotto C, De Rosa G, Chatfield KC, Gelb BD, Calcagni G
Am J Med Genet C Semin Med Genet 2022 Dec;190(4):440-451. Epub 2022 Nov 21 doi: 10.1002/ajmg.c.32014. PMID: 36408797
Lioncino M, Monda E, Verrillo F, Moscarella E, Calcagni G, Drago F, Marino B, Digilio MC, Putotto C, Calabrò P, Russo MG, Roberts AE, Gelb BD, Tartaglia M, Limongelli G
Heart Fail Clin 2022 Jan;18(1):19-29. Epub 2021 Oct 25 doi: 10.1016/j.hfc.2021.07.004. PMID: 34776080Free PMC Article
Patnaik MM, Lasho TL
Hematology Am Soc Hematol Educ Program 2020 Dec 4;2020(1):450-459. doi: 10.1182/hematology.2020000130. PMID: 33275756Free PMC Article
Linglart L, Gelb BD
Am J Med Genet C Semin Med Genet 2020 Mar;184(1):73-80. Epub 2020 Feb 5 doi: 10.1002/ajmg.c.31765. PMID: 32022400Free PMC Article
Kiel C, Serrano L
Mol Syst Biol 2014 May 6;10(5):727. doi: 10.1002/msb.20145092. PMID: 24803665Free PMC Article

Clinical prediction guides

Kwon JJ, Hajian B, Bian Y, Young LC, Amor AJ, Fuller JR, Fraley CV, Sykes AM, So J, Pan J, Baker L, Lee SJ, Wheeler DB, Mayhew DL, Persky NS, Yang X, Root DE, Barsotti AM, Stamford AW, Perry CK, Burgin A, McCormick F, Lemke CT, Hahn WC, Aguirre AJ
Nature 2022 Sep;609(7926):408-415. Epub 2022 Jul 13 doi: 10.1038/s41586-022-04928-2. PMID: 35831509Free PMC Article
Hathaway J, Heliö K, Saarinen I, Tallila J, Seppälä EH, Tuupanen S, Turpeinen H, Kangas-Kontio T, Schleit J, Tommiska J, Kytölä V, Valori M, Muona M, Sistonen J, Gentile M, Salmenperä P, Myllykangas S, Paananen J, Alastalo TP, Heliö T, Koskenvuo J
BMC Cardiovasc Disord 2021 Mar 5;21(1):126. doi: 10.1186/s12872-021-01927-5. PMID: 33673806Free PMC Article
Athota JP, Bhat M, Nampoothiri S, Gowrishankar K, Narayanachar SG, Puttamallesh V, Farooque MO, Shetty S
BMC Med Genet 2020 Mar 12;21(1):50. doi: 10.1186/s12881-020-0986-5. PMID: 32164556Free PMC Article
Halaban R, Krauthammer M
J Invest Dermatol 2016 Sep;136(9):1755-1759. Epub 2016 May 25 doi: 10.1016/j.jid.2016.05.095. PMID: 27236105Free PMC Article
Kiel C, Serrano L
Mol Syst Biol 2014 May 6;10(5):727. doi: 10.1002/msb.20145092. PMID: 24803665Free PMC Article

Recent systematic reviews

Debbaut E, Steyaert J, El Bakkali M
Mol Genet Genomic Med 2024 Apr;12(4):e2428. doi: 10.1002/mgg3.2428. PMID: 38581124Free PMC Article
Makhamreh MM, Shivashankar K, Araji S, Critchlow E, O'Brien BM, Wodoslawsky S, Berger SI, Al-Kouatly HB
Am J Med Genet A 2024 May;194(5):e63494. Epub 2023 Dec 29 doi: 10.1002/ajmg.a.63494. PMID: 38156365
Scala M, Fiaschi P, Capra V, Garrè ML, Tortora D, Ravegnani M, Pavanello M
Childs Nerv Syst 2018 Jul;34(7):1311-1323. Epub 2018 May 24 doi: 10.1007/s00381-018-3833-7. PMID: 29797062
Bader-Meunier B, Cavé H, Jeremiah N, Magerus A, Lanzarotti N, Rieux-Laucat F, Cormier-Daire V
Semin Arthritis Rheum 2013 Oct;43(2):217-9. Epub 2013 Jun 17 doi: 10.1016/j.semarthrit.2013.04.009. PMID: 23786871
Gripp KW, Hopkins E, Doyle D, Dobyns WB
Am J Med Genet A 2010 May;152A(5):1161-8. doi: 10.1002/ajmg.a.33391. PMID: 20425820Free PMC Article

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