MCID: NNN026
MIFTS: 50

Noonan Syndrome with Multiple Lentigines

Categories: Eye diseases, Cardiovascular diseases, Ear diseases, Skin diseases, Fetal diseases, Rare diseases, Genetic diseases

Aliases & Classifications for Noonan Syndrome with Multiple Lentigines

MalaCards integrated aliases for Noonan Syndrome with Multiple Lentigines:

Name: Noonan Syndrome with Multiple Lentigines 23 25 56 29
Leopard Syndrome 23 25 56 69
Multiple Lentigines Syndrome 23 25
Cardiomyopathic Lentiginosis 25 56
Lentiginosis Profusa 25 69
Alopecia Epilepsy Oligophrenia Syndrome of Moynahan 69
Progressive Cardiomyopathic Lentiginosis 25
Familial Multiple Lentigines Syndrome 56
Cardio-Cutaneous Syndrome 25
Diffuse Lentiginosis 25
Moynahan Syndrome 25
Nsml 25

Characteristics:

Orphanet epidemiological data:

56
noonan syndrome with multiple lentigines
Inheritance: Autosomal dominant; Age of onset: Childhood;

GeneReviews:

23
Penetrance Penetrance of nsml is difficult to determine because of ascertainment bias and variable expressivity, frequently with subtlety of phenotypic features. affected adults may be diagnosed only after the birth of a more obviously affected infant...

Classifications:



Summaries for Noonan Syndrome with Multiple Lentigines

Genetics Home Reference : 25 Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome) is a condition that affects many areas of the body. As the condition name suggests, Noonan syndrome with multiple lentigines is very similar to a condition called Noonan syndrome, and it can be difficult to tell the two disorders apart in early childhood. However, the features of these two conditions differ later in life. The characteristic features of Noonan syndrome with multiple lentigines include brown skin spots called lentigines that are similar to freckles, heart defects, widely spaced eyes (ocular hypertelorism), a sunken chest (pectus excavatum) or protruding chest (pectus carinatum), and short stature. These features vary, however, even among affected individuals in the same family. Not all individuals with Noonan syndrome with multiple lentigines have all the characteristic features of this condition.

MalaCards based summary : Noonan Syndrome with Multiple Lentigines, also known as leopard syndrome, is related to leopard syndrome and noonan syndrome 1, and has symptoms including cryptorchidism, hypospadias and decreased fertility. An important gene associated with Noonan Syndrome with Multiple Lentigines is PTPN11 (Protein Tyrosine Phosphatase, Non-Receptor Type 11), and among its related pathways/superpathways are Regulation of lipid metabolism Insulin signaling-generic cascades and Development HGF signaling pathway. Affiliated tissues include skin, heart and eye, and related phenotypes are Increased shRNA abundance (Z-score > 2) and cardiovascular system

Wikipedia : 72 Noonan syndrome with multiple lentigines (NSML) (also known as LEOPARD syndrome, cardiocutaneous... more...

GeneReviews: NBK1383

Related Diseases for Noonan Syndrome with Multiple Lentigines

Graphical network of the top 20 diseases related to Noonan Syndrome with Multiple Lentigines:



Diseases related to Noonan Syndrome with Multiple Lentigines

Symptoms & Phenotypes for Noonan Syndrome with Multiple Lentigines

Human phenotypes related to Noonan Syndrome with Multiple Lentigines:

56 32 (show top 50) (show all 51)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 cryptorchidism 56 32 frequent (33%) Frequent (79-30%) HP:0000028
2 hypospadias 56 32 occasional (7.5%) Occasional (29-5%) HP:0000047
3 decreased fertility 56 32 frequent (33%) Frequent (79-30%) HP:0000144
4 brachycephaly 56 32 occasional (7.5%) Occasional (29-5%) HP:0000248
5 hypertelorism 56 32 hallmark (90%) Very frequent (99-80%) HP:0000316
6 triangular face 56 32 occasional (7.5%) Occasional (29-5%) HP:0000325
7 low-set, posteriorly rotated ears 56 32 frequent (33%) Frequent (79-30%) HP:0000368
8 wide nasal bridge 56 32 frequent (33%) Frequent (79-30%) HP:0000431
9 webbed neck 56 32 frequent (33%) Frequent (79-30%) HP:0000465
10 ptosis 56 32 frequent (33%) Frequent (79-30%) HP:0000508
11 pectus excavatum 56 32 frequent (33%) Frequent (79-30%) HP:0000767
12 pectus carinatum 56 32 frequent (33%) Frequent (79-30%) HP:0000768
13 sprengel anomaly 56 32 frequent (33%) Frequent (79-30%) HP:0000912
14 hyperextensible skin 56 32 hallmark (90%) Very frequent (99-80%) HP:0000974
15 melanocytic nevus 56 32 hallmark (90%) Very frequent (99-80%) HP:0000995
16 multiple lentigines 56 32 hallmark (90%) Very frequent (99-80%) HP:0001003
17 intellectual disability, mild 56 32 occasional (7.5%) Occasional (29-5%) HP:0001256
18 global developmental delay 56 32 occasional (7.5%) Occasional (29-5%) HP:0001263
19 freckling 56 32 hallmark (90%) Very frequent (99-80%) HP:0001480
20 subcutaneous nodule 56 32 occasional (7.5%) Occasional (29-5%) HP:0001482
21 intrauterine growth retardation 56 32 hallmark (90%) Very frequent (99-80%) HP:0001511
22 abnormality of the voice 56 32 occasional (7.5%) Occasional (29-5%) HP:0001608
23 mitral valve prolapse 56 32 frequent (33%) Frequent (79-30%) HP:0001634
24 hypertrophic cardiomyopathy 56 32 hallmark (90%) Very frequent (99-80%) HP:0001639
25 pulmonic stenosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0001642
26 myocardial infarction 56 32 occasional (7.5%) Occasional (29-5%) HP:0001658
27 scoliosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0002650
28 melanoma 56 32 occasional (7.5%) Occasional (29-5%) HP:0002861
29 myelodysplasia 56 32 occasional (7.5%) Occasional (29-5%) HP:0002863
30 neuroblastoma 56 32 occasional (7.5%) Occasional (29-5%) HP:0003006
31 spina bifida occulta 56 32 occasional (7.5%) Occasional (29-5%) HP:0003298
32 scapular winging 56 32 frequent (33%) Frequent (79-30%) HP:0003691
33 abnormality of the endocardium 56 32 occasional (7.5%) Occasional (29-5%) HP:0004306
34 short stature 56 32 frequent (33%) Frequent (79-30%) HP:0004322
35 abnormality of the pulmonary artery 56 32 hallmark (90%) Very frequent (99-80%) HP:0004414
36 atrioventricular canal defect 56 32 frequent (33%) Frequent (79-30%) HP:0006695
37 excessive wrinkled skin 56 32 occasional (7.5%) Occasional (29-5%) HP:0007392
38 severe sensorineural hearing impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0008625
39 aplasia/hypoplasia of the abdominal wall musculature 56 32 occasional (7.5%) Occasional (29-5%) HP:0010318
40 bundle branch block 56 32 hallmark (90%) Very frequent (99-80%) HP:0011710
41 abnormal localization of kidney 56 32 occasional (7.5%) Occasional (29-5%) HP:0100542
42 abnormality of the genital system 56 Very frequent (99-80%)
43 abnormality of the face 56 Frequent (79-30%)
44 sensorineural hearing impairment 56 Very frequent (99-80%)
45 growth delay 56 Very frequent (99-80%)
46 abnormality of the mitral valve 56 Frequent (79-30%)
47 abnormality of the pulmonary valve 56 Very frequent (99-80%)
48 malformation of the heart and great vessels 56 Frequent (79-30%)
49 aneurysm 56 Occasional (29-5%)
50 arrhythmia 56 Very frequent (99-80%)

UMLS symptoms related to Noonan Syndrome with Multiple Lentigines:


hyposmia, seizures

GenomeRNAi Phenotypes related to Noonan Syndrome with Multiple Lentigines according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-110 10.02 BRAF
2 Increased shRNA abundance (Z-score > 2) GR00366-A-118 10.02 PTPN11
3 Increased shRNA abundance (Z-score > 2) GR00366-A-121 10.02 PTPN11
4 Increased shRNA abundance (Z-score > 2) GR00366-A-138 10.02 PTPN11
5 Increased shRNA abundance (Z-score > 2) GR00366-A-149 10.02 RAF1 BRAF PTPN11
6 Increased shRNA abundance (Z-score > 2) GR00366-A-151 10.02 RAF1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-161 10.02 RAF1
8 Increased shRNA abundance (Z-score > 2) GR00366-A-166 10.02 BRAF
9 Increased shRNA abundance (Z-score > 2) GR00366-A-177 10.02 BRAF
10 Increased shRNA abundance (Z-score > 2) GR00366-A-178 10.02 PTPN11
11 Increased shRNA abundance (Z-score > 2) GR00366-A-190 10.02 PTPN11
12 Increased shRNA abundance (Z-score > 2) GR00366-A-194 10.02 BRAF
13 Increased shRNA abundance (Z-score > 2) GR00366-A-29 10.02 BRAF
14 Increased shRNA abundance (Z-score > 2) GR00366-A-31 10.02 BRAF
15 Increased shRNA abundance (Z-score > 2) GR00366-A-32 10.02 BRAF
16 Increased shRNA abundance (Z-score > 2) GR00366-A-37 10.02 PTPN11
17 Increased shRNA abundance (Z-score > 2) GR00366-A-47 10.02 BRAF PTPN11
18 Increased shRNA abundance (Z-score > 2) GR00366-A-52 10.02 RAF1
19 Increased shRNA abundance (Z-score > 2) GR00366-A-7 10.02 PTPN11
20 Increased shRNA abundance (Z-score > 2) GR00366-A-78 10.02 PTPN11
21 Increased simian virus 40 (SV40) infection GR00356-A-2 8.62 BRAF RAF1

MGI Mouse Phenotypes related to Noonan Syndrome with Multiple Lentigines:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.67 PPP1R13L PTPN11 RAF1 BRAF
2 endocrine/exocrine gland MP:0005379 9.62 BRAF PPP1R13L PTPN11 RAF1
3 integument MP:0010771 9.46 BRAF PPP1R13L PTPN11 RAF1
4 hearing/vestibular/ear MP:0005377 9.43 BRAF PTPN11 RAF1
5 muscle MP:0005369 9.26 BRAF PPP1R13L PTPN11 RAF1
6 vision/eye MP:0005391 8.92 BRAF PPP1R13L PTPN11 RAF1

Drugs & Therapeutics for Noonan Syndrome with Multiple Lentigines

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes Not yet recruiting NCT02486731

Search NIH Clinical Center for Noonan Syndrome with Multiple Lentigines

Genetic Tests for Noonan Syndrome with Multiple Lentigines

Genetic tests related to Noonan Syndrome with Multiple Lentigines:

id Genetic test Affiliating Genes
1 Noonan Syndrome with Multiple Lentigines 29

Anatomical Context for Noonan Syndrome with Multiple Lentigines

MalaCards organs/tissues related to Noonan Syndrome with Multiple Lentigines:

39
Skin, Heart, Eye, Kidney

Publications for Noonan Syndrome with Multiple Lentigines

Articles related to Noonan Syndrome with Multiple Lentigines:

(show all 11)
id Title Authors Year
1
Heterozygous deletion of AKT1 rescues cardiac contractility, but not hypertrophy, in a mouse model of Noonan Syndrome with Multiple Lentigines. ( 28911943 )
2017
2
In vivo efficacy of the AKT inhibitor ARQ 092 in Noonan Syndrome with multiple lentigines-associated hypertrophic cardiomyopathy. ( 28582432 )
2017
3
Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11. ( 28483241 )
2017
4
Noonan syndrome with multiple lentigines with PTPN11 (T468M) gene mutation accompanied with solitary granular cell tumor. ( 28681392 )
2017
5
Multiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines. ( 27238887 )
2016
6
Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines. ( 27348588 )
2016
7
Hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26952712 )
2016
8
Rapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: Palliative treatment with a rapamycin analog. ( 25708222 )
2015
9
A novel heterozygous MAP2K1 mutation in a patient with Noonan syndrome with multiple lentigines. ( 25423878 )
2015
10
Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26337637 )
2015
11
Elevated calcium transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan Syndrome with Multiple Lentigines. ( 25724491 )
2015

Variations for Noonan Syndrome with Multiple Lentigines

ClinVar genetic disease variations for Noonan Syndrome with Multiple Lentigines:

6 (show all 11)
id Gene Variation Type Significance SNP ID Assembly Location
1 PTPN11 NM_002834.4(PTPN11): c.1403C> T (p.Thr468Met) single nucleotide variant Pathogenic/Likely pathogenic rs121918457 GRCh37 Chromosome 12, 112926270: 112926270
2 PTPN11 NM_002834.4(PTPN11): c.1381G> A (p.Ala461Thr) single nucleotide variant Pathogenic rs121918468 GRCh37 Chromosome 12, 112926248: 112926248
3 RAF1 NM_002880.3(RAF1): c.770C> T (p.Ser257Leu) single nucleotide variant Pathogenic/Likely pathogenic rs80338796 GRCh37 Chromosome 3, 12645699: 12645699
4 RAF1 NM_002880.3(RAF1): c.1837C> G (p.Leu613Val) single nucleotide variant Pathogenic/Likely pathogenic rs80338797 GRCh37 Chromosome 3, 12626123: 12626123
5 RAF1 NM_002880.3(RAF1): c.1456G> A (p.Asp486Asn) single nucleotide variant Pathogenic rs80338798 GRCh37 Chromosome 3, 12627260: 12627260
6 RAF1 NM_002880.3(RAF1): c.1472C> T (p.Thr491Ile) single nucleotide variant Pathogenic/Likely pathogenic rs80338799 GRCh37 Chromosome 3, 12627244: 12627244
7 BRAF NM_004333.4(BRAF): c.721A> C (p.Thr241Pro) single nucleotide variant Pathogenic/Likely pathogenic rs387906661 GRCh37 Chromosome 7, 140501351: 140501351
8 BRAF NM_004333.4(BRAF): c.735A> T (p.Leu245Phe) single nucleotide variant Pathogenic/Likely pathogenic rs397507466 GRCh37 Chromosome 7, 140501337: 140501337
9 PTPN11 NM_002834.4(PTPN11): c.1381G> T (p.Ala461Ser) single nucleotide variant Pathogenic rs121918468 GRCh37 Chromosome 12, 112926248: 112926248
10 PTPN11 NM_002834.4(PTPN11): c.1517A> C (p.Gln506Pro) single nucleotide variant Pathogenic rs397507548 GRCh37 Chromosome 12, 112926897: 112926897
11 PPP1R13L NM_001142502.1(PPP1R13L): c.2241C> G (p.Tyr747Ter) single nucleotide variant Pathogenic rs1114167453 GRCh38 Chromosome 19, 45385569: 45385569

Expression for Noonan Syndrome with Multiple Lentigines

Search GEO for disease gene expression data for Noonan Syndrome with Multiple Lentigines.

Pathways for Noonan Syndrome with Multiple Lentigines

Pathways related to Noonan Syndrome with Multiple Lentigines according to GeneCards Suite gene sharing:

(show all 44)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.58 BRAF PTPN11 RAF1
2
Show member pathways
12.45 BRAF PTPN11 RAF1
3
Show member pathways
12.44 BRAF PTPN11 RAF1
4
Show member pathways
12.36 BRAF PTPN11 RAF1
5
Show member pathways
12.09 BRAF PTPN11 RAF1
6
Show member pathways
11.94 BRAF PTPN11 RAF1
7
Show member pathways
11.87 BRAF PTPN11 RAF1
8 11.85 PTPN11 RAF1
9
Show member pathways
11.83 BRAF RAF1
10
Show member pathways
11.82 BRAF RAF1
11
Show member pathways
11.81 PTPN11 RAF1
12 11.8 BRAF RAF1
13
Show member pathways
11.77 BRAF RAF1
14 11.74 BRAF PTPN11 RAF1
15 11.72 BRAF RAF1
16 11.71 BRAF RAF1
17
Show member pathways
11.7 PTPN11 RAF1
18 11.69 BRAF RAF1
19 11.67 BRAF RAF1
20 11.65 BRAF RAF1
21
Show member pathways
11.64 PTPN11 RAF1
22 11.63 PTPN11 RAF1
23 11.62 BRAF RAF1
24 11.57 BRAF RAF1
25
Show member pathways
11.56 BRAF RAF1
26 11.55 BRAF PTPN11 RAF1
27 11.49 BRAF RAF1
28 11.45 BRAF RAF1
29
Show member pathways
11.42 BRAF RAF1
30
Show member pathways
11.39 BRAF RAF1
31
Show member pathways
11.39 BRAF PTPN11 RAF1
32 11.38 BRAF RAF1
33 11.37 BRAF RAF1
34 11.3 BRAF RAF1
35 11.28 BRAF RAF1
36 11.26 BRAF RAF1
37 11.18 PTPN11 RAF1
38 11.17 PTPN11 RAF1
39 11.03 PTPN11 RAF1
40
Show member pathways
10.99 BRAF RAF1
41
Show member pathways
10.95 PTPN11 RAF1
42 10.9 PTPN11 RAF1
43 10.84 BRAF RAF1
44 10.83 BRAF PTPN11 RAF1

GO Terms for Noonan Syndrome with Multiple Lentigines

Biological processes related to Noonan Syndrome with Multiple Lentigines according to GeneCards Suite gene sharing:

(show all 11)
id Name GO ID Score Top Affiliating Genes
1 platelet activation GO:0030168 9.49 PTPN11 RAF1
2 multicellular organism growth GO:0035264 9.48 PPP1R13L PTPN11
3 positive regulation of peptidyl-serine phosphorylation GO:0033138 9.46 BRAF RAF1
4 negative regulation of signal transduction GO:0009968 9.43 BRAF RAF1
5 somatic stem cell population maintenance GO:0035019 9.4 BRAF RAF1
6 activation of MAPKK activity GO:0000186 9.37 BRAF RAF1
7 thymus development GO:0048538 9.32 BRAF RAF1
8 thyroid gland development GO:0030878 9.26 BRAF RAF1
9 face development GO:0060324 9.16 BRAF RAF1
10 neurotrophin TRK receptor signaling pathway GO:0048011 8.96 PTPN11 RAF1
11 positive regulation of ERK1 and ERK2 cascade GO:0070374 8.8 BRAF PTPN11 RAF1

Molecular functions related to Noonan Syndrome with Multiple Lentigines according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 identical protein binding GO:0042802 9.5 BRAF PPP1R13L RAF1
2 signal transducer activity, downstream of receptor GO:0005057 9.26 BRAF RAF1
3 MAP kinase kinase kinase activity GO:0004709 9.16 BRAF RAF1
4 small GTPase binding GO:0031267 8.96 BRAF RAF1
5 mitogen-activated protein kinase kinase binding GO:0031434 8.62 BRAF RAF1

Sources for Noonan Syndrome with Multiple Lentigines

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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