Details of Disease | DrugMAP

General Information of Disease (ID: DIS014D0)

Disease Name	Noonan syndrome with multiple lentigines
Synonyms	Moynahan syndrome; lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, Deafnes; Capute-Rimoin-Konigsmark-Esterly-Richardson syndrome; familial multiple lentigines syndrome; generalized lentiginosis; LEOPARD syndrome; Noonan syndrome with multiple lentigines; Gorlin syndrome II; lentiginosis profusa syndrome; progressive cardiomyopathic lentiginosis; Cardiomyopathic lentiginosis; generalised lentiginosis; lentigines, electrocardiographic conduction defects, 0cular hypertelorism, pulmonary stenosis, abnormalities of the genitals, retarded Growth, deafness
Definition	A rare multisystem genetic disorder characterized by lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features.
Disease Hierarchy	DIS6SVEE: Syndromic disease DISTATYK: Noonan syndrome and Noonan-related syndrome DISD0WVL: Multiple congenital anomalies/dysmorphic syndrome without intellectual disability DIS3HIWD: Autosomal dominant disease DIS014D0: Noonan syndrome with multiple lentigines
Disease Identifiers	MONDO ID MONDO_0007893 MESH ID D044542 UMLS CUI C0175704 MedGen ID 104494 Orphanet ID 500 SNOMED CT ID 111306001

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 11 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BRAF	TT0EOB8	Limited	Biomarker	[1]
KRAS	TTM8FR7	Limited	Genetic Variation	[2]
MAP2K1	TTIDAPM	Limited	Biomarker	[3]
NRAS	TTW2R9X	Limited	Autosomal dominant	[4]
NRAS	TTW2R9X	Limited	Biomarker	[5]
RAF1	TTAN5W2	Limited	Genetic Variation	[6]
BRAF	TT0EOB8	Supportive	Autosomal dominant	[7]
RAF1	TTB18GJ	Supportive	Autosomal dominant	[7]
EPHA2	TTRJB2G	Strong	Genetic Variation	[8]
MAP2K1	TTIDAPM	Strong	Autosomal dominant	[9]
PTPN11	TT7WUAV	Definitive	Autosomal dominant	[4]
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⏷ Show the Full List of 11 DTT(s)

This Disease Is Related to 11 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
NFATC4	OTTDCUAO	Limited	Biomarker	[10]
NRAS	OTVQ1DG3	Limited	Autosomal dominant	[4]
SASH1	OTQA8BD4	Limited	Biomarker	[11]
SHOC2	OTUNQ2CT	Limited	Genetic Variation	[2]
SOS1	OTTCWXC3	Limited	Genetic Variation	[12]
TESC	OTI8C76M	Limited	Genetic Variation	[13]
BRAF	OT7S81XQ	Supportive	Autosomal dominant	[7]
RAF1	OT51LSFO	Supportive	Autosomal dominant	[7]
MAP2K1	OT4Y9NQI	Strong	Autosomal dominant	[9]
PPP1R13L	OTNCPLWE	Strong	Biomarker	[14]
PTPN11	OTFH9M73	Definitive	Autosomal dominant	[4]
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⏷ Show the Full List of 11 DOT(s)

References

1	Targeted/exome sequencing identified mutations in ten Chinese patients diagnosed with Noonan syndrome and related disorders.BMC Med Genomics. 2017 Oct 30;10(1):62. doi: 10.1186/s12920-017-0298-6.
2	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.
3	A novel heterozygous MAP2K1 mutation in a patient with Noonan syndrome with multiple lentigines.Am J Med Genet A. 2015 Feb;167A(2):407-11. doi: 10.1002/ajmg.a.36842. Epub 2014 Nov 25.
4	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.
5	Mutation in NRAS in familial Noonan syndrome--case report and review of the literature.BMC Med Genet. 2015 Oct 14;16:95. doi: 10.1186/s12881-015-0239-1.
6	RAF1 variant in a patient with Noonan syndrome with multiple lentigines and craniosynostosis.Am J Med Genet A. 2019 Aug;179(8):1598-1602. doi: 10.1002/ajmg.a.61203. Epub 2019 May 30.
7	Noonan Syndrome with Multiple Lentigines. 2007 Nov 30 [updated 2022 Jun 30]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
8	Involvement of EphA2-mediated tyrosine phosphorylation of Shp2 in Shp2-regulated activation of extracellular signal-regulated kinase.Oncogene. 2013 Nov 7;32(45):5292-301. doi: 10.1038/onc.2012.571. Epub 2013 Jan 14.
9	Noonan syndrome and clinically related disorders. Best Pract Res Clin Endocrinol Metab. 2011 Feb;25(1):161-79. doi: 10.1016/j.beem.2010.09.002.
10	Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome.Nature. 2010 Jun 10;465(7299):808-12. doi: 10.1038/nature09005.
11	Lentiginous phenotypes caused by diverse pathogenic genes (SASH1 and PTPN11): clinical and molecular discrimination.Clin Genet. 2016 Oct;90(4):372-7. doi: 10.1111/cge.12728. Epub 2016 Feb 3.
12	A rasopathy phenotype with severe congenital hypertrophic obstructive cardiomyopathy associated with a PTPN11 mutation and a novel variant in SOS1.Am J Med Genet A. 2012 Jun;158A(6):1414-21. doi: 10.1002/ajmg.a.35363. Epub 2012 May 14.
13	Conservation of structural and functional elements of TSC1 and TSC2: a bioinformatic comparison across animal models.Behav Genet. 2011 May;41(3):349-56. doi: 10.1007/s10519-010-9440-3. Epub 2011 Jan 18.
14	iASPP, a previously unidentified regulator of desmosomes, prevents arrhythmogenic right ventricular cardiomyopathy (ARVC)-induced sudden death.Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):E973-81. doi: 10.1073/pnas.1408111112. Epub 2015 Feb 17.