{"id":27146,"date":"2024-05-26T14:18:31","date_gmt":"2024-05-26T12:18:31","guid":{"rendered":"https:\/\/www.krebs-praedisposition.de\/?post_type=kompendium&p=27146"},"modified":"2025-08-26T12:33:57","modified_gmt":"2025-08-26T10:33:57","slug":"noonan-syndrom","status":"publish","type":"kompendium","link":"https:\/\/www.krebs-praedisposition.de\/en\/kompendium\/noonan-syndrom\/","title":{"rendered":"Noonan Syndrome"},"content":{"rendered":"

Noonan Syndrome \u2013\u00a0Definition<\/h2><\/div>
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Noonan syndrome (OMIM #163950) is an autosomal-dominant, hereditary developmental disorder with a distinct phenotype (see the clinical features) and a slightly increased risk of cancer.<\/p>\n<\/div>

Synonym:<\/p>\n<\/div><\/div><\/div>

NS<\/p>\n<\/div><\/div><\/div><\/div>

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Genes:<\/p>\n<\/div><\/div><\/div>

PTPN11<\/em> (50%), SOS1<\/i> (13%), RAF1<\/i> (5%), RIT1<\/i> (5%), rarer: KRAS<\/i>, NRAS<\/i>, BRAF<\/i>, MAP2K1<\/i>, RRAS<\/i>, RASA2<\/i>, A2ML1<\/i>, SOS2<\/i>, LZTR1<\/i>, CBL<\/i>, SHOC2<\/i>, PPP1CB<\/i><\/p>\n<\/div><\/div><\/div><\/div>

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Gen\u00ade products:<\/p>\n<\/div><\/div><\/div>

SHP2, SOS1, RAF1, RIT1, KRAS, NRAS, BRAF, MAP2K1, RRAS, RASA2, A2ML1, SOS2, LZTR1, CBL, SHOC2, PPP1CB<\/p>\n<\/div><\/div><\/div><\/div>

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Function:<\/p>\n<\/div><\/div><\/div>

RAS signaling pathway<\/p>\n<\/div><\/div><\/div><\/div>

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Pattern of inheritance:<\/p>\n<\/div><\/div><\/div>

Autosomal dominant<\/p>\n<\/div><\/div><\/div><\/div>

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Prevalence:<\/p>\n<\/div><\/div><\/div>

1:2.000<\/p>\n<\/div><\/div><\/div><\/div>

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Genotype-phenotype correlation:<\/p>\n<\/div><\/div><\/div>

Specific pathogenic variants in PTPN11<\/em> (e.g. codon 61 or T73I) or KRAS<\/em> (T58I): risk of a myeloproliferative disorder
\nSpecific pathogenic variants in SHOC2<\/em> (S2G) or PPP1CB<\/em> (P49R): Noonan syndrome-like disease with loose anagen hair (NSLAH)
\nSpecific pathogenic variants in PTPN11<\/em> (T468M and Y279C): Noonan syndrome with multiple lentigines (NSML)
\nPathogenic variants in CBL<\/em>: CBL syndrome (CBLS)<\/p>\n<\/div><\/div><\/div><\/div>

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Penetrance:<\/p>\n<\/div><\/div><\/div>

Nearly 100% (relates to the syndrome and not to the development of neoplasia)<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/div>

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Overview of the Chapters on This Page:<\/h4><\/div><\/div><\/div>