MCID: NNN026
MIFTS: 49

Noonan Syndrome with Multiple Lentigines

Categories: Genetic diseases, Cardiovascular diseases, Eye diseases, Ear diseases, Skin diseases, Fetal diseases, Rare 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 24 55 28
Leopard Syndrome 23 24 55 69
Multiple Lentigines Syndrome 23 24
Cardiomyopathic Lentiginosis 24 55
Lentiginosis Profusa 24 69
Alopecia Epilepsy Oligophrenia Syndrome of Moynahan 69
Progressive Cardiomyopathic Lentiginosis 24
Familial Multiple Lentigines Syndrome 55
Cardio-Cutaneous Syndrome 24
Diffuse Lentiginosis 24
Moynahan Syndrome 24
Nsml 24

Characteristics:

Orphanet epidemiological data:

55
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 : 24 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 noonan syndrome 1 and leopard syndrome, 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 Common Cytokine Receptor Gamma-Chain Family Signaling Pathways. Affiliated tissues include skin, heart and eye, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

GeneReviews: NBK1383

Related Diseases for Noonan Syndrome with Multiple Lentigines

Diseases related to Noonan Syndrome with Multiple Lentigines via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 18)
# Related Disease Score Top Affiliating Genes
1 noonan syndrome 1 31.4 BRAF PTPN11 RAF1
2 leopard syndrome 30.2 BRAF PPP1R13L PTPN11 RAF1
3 lentigines 29.9 BRAF PTPN11 RAF1
4 lentiginosis, inherited patterned 11.7
5 alopecia-epilepsy-oligophrenia syndrome of moynahan 11.1
6 leopard syndrome 1 10.5
7 pseudo-turner syndrome 10.5
8 hypertrophic cardiomyopathy 10.1
9 neuropathy 10.1
10 craniosynostosis 10.0
11 granular cell tumor 10.0
12 neurofibroma 10.0
13 dengue disease 9.7 PTPN11 RAF1
14 cardiofaciocutaneous syndrome 1 9.6 BRAF PTPN11
15 pulmonic stenosis 9.5 BRAF PTPN11 RAF1
16 hypertelorism 9.5 BRAF PTPN11 RAF1
17 pilocytic astrocytoma 9.4 BRAF PTPN11 RAF1
18 juvenile myelomonocytic leukemia 9.3 BRAF PTPN11 RAF1

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:

55 31 (show top 50) (show all 53)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 cryptorchidism 55 31 frequent (33%) Frequent (79-30%) HP:0000028
2 hypospadias 55 31 occasional (7.5%) Occasional (29-5%) HP:0000047
3 decreased fertility 55 31 frequent (33%) Frequent (79-30%) HP:0000144
4 brachycephaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0000248
5 hypertelorism 55 31 hallmark (90%) Very frequent (99-80%) HP:0000316
6 triangular face 55 31 occasional (7.5%) Occasional (29-5%) HP:0000325
7 low-set, posteriorly rotated ears 55 31 frequent (33%) Frequent (79-30%) HP:0000368
8 wide nasal bridge 55 31 frequent (33%) Frequent (79-30%) HP:0000431
9 webbed neck 55 31 frequent (33%) Frequent (79-30%) HP:0000465
10 ptosis 55 31 frequent (33%) Frequent (79-30%) HP:0000508
11 pectus excavatum 55 31 frequent (33%) Frequent (79-30%) HP:0000767
12 pectus carinatum 55 31 frequent (33%) Frequent (79-30%) HP:0000768
13 sprengel anomaly 55 31 frequent (33%) Frequent (79-30%) HP:0000912
14 hyperextensible skin 55 31 hallmark (90%) Very frequent (99-80%) HP:0000974
15 melanocytic nevus 55 31 hallmark (90%) Very frequent (99-80%) HP:0000995
16 multiple lentigines 55 31 hallmark (90%) Very frequent (99-80%) HP:0001003
17 intellectual disability, mild 55 31 occasional (7.5%) Occasional (29-5%) HP:0001256
18 global developmental delay 55 31 occasional (7.5%) Occasional (29-5%) HP:0001263
19 freckling 55 31 hallmark (90%) Very frequent (99-80%) HP:0001480
20 subcutaneous nodule 55 31 occasional (7.5%) Occasional (29-5%) HP:0001482
21 intrauterine growth retardation 55 31 hallmark (90%) Very frequent (99-80%) HP:0001511
22 abnormality of the voice 55 31 occasional (7.5%) Occasional (29-5%) HP:0001608
23 mitral valve prolapse 55 31 frequent (33%) Frequent (79-30%) HP:0001634
24 hypertrophic cardiomyopathy 55 31 hallmark (90%) Very frequent (99-80%) HP:0001639
25 pulmonic stenosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0001642
26 myocardial infarction 55 31 occasional (7.5%) Occasional (29-5%) HP:0001658
27 scoliosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0002650
28 melanoma 55 31 occasional (7.5%) Occasional (29-5%) HP:0002861
29 myelodysplasia 55 31 occasional (7.5%) Occasional (29-5%) HP:0002863
30 neuroblastoma 55 31 occasional (7.5%) Occasional (29-5%) HP:0003006
31 spina bifida occulta 55 31 occasional (7.5%) Occasional (29-5%) HP:0003298
32 scapular winging 55 31 frequent (33%) Frequent (79-30%) HP:0003691
33 short stature 55 31 frequent (33%) Frequent (79-30%) HP:0004322
34 abnormality of the pulmonary artery 55 31 hallmark (90%) Very frequent (99-80%) HP:0004414
35 atrioventricular canal defect 55 31 frequent (33%) Frequent (79-30%) HP:0006695
36 excessive wrinkled skin 55 31 occasional (7.5%) Occasional (29-5%) HP:0007392
37 severe sensorineural hearing impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0008625
38 aplasia/hypoplasia of the abdominal wall musculature 55 31 occasional (7.5%) Occasional (29-5%) HP:0010318
39 arrhythmia 55 31 hallmark (90%) Very frequent (99-80%) HP:0011675
40 bundle branch block 55 31 hallmark (90%) Very frequent (99-80%) HP:0011710
41 abnormal localization of kidney 55 31 occasional (7.5%) Occasional (29-5%) HP:0100542
42 abnormality of the genital system 55 Very frequent (99-80%)
43 abnormality of the face 55 Frequent (79-30%)
44 sensorineural hearing impairment 55 Very frequent (99-80%)
45 growth delay 55 Very frequent (99-80%)
46 abnormality of the mitral valve 55 Frequent (79-30%)
47 abnormality of the pulmonary valve 55 Very frequent (99-80%)
48 malformation of the heart and great vessels 55 Frequent (79-30%)
49 aneurysm 55 Occasional (29-5%)
50 abnormality of the endocardium 55 Occasional (29-5%)

UMLS symptoms related to Noonan Syndrome with Multiple Lentigines:


seizures, hyposmia

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

25 (show all 21)
# 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 PTPN11 RAF1 BRAF
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 PTPN11 BRAF
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:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.67 BRAF PPP1R13L PTPN11 RAF1
2 endocrine/exocrine gland MP:0005379 9.62 BRAF PPP1R13L PTPN11 RAF1
3 integument MP:0010771 9.46 PPP1R13L PTPN11 RAF1 BRAF
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:


# 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:

# Genetic test Affiliating Genes
1 Noonan Syndrome with Multiple Lentigines 28

Anatomical Context for Noonan Syndrome with Multiple Lentigines

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

38
Skin, Heart, Eye, Kidney

Publications for Noonan Syndrome with Multiple Lentigines

Articles related to Noonan Syndrome with Multiple Lentigines:

(show all 12)
# Title Authors Year
1
Noonan syndrome with multiple lentigines and associated craniosynostosis. ( 29356064 )
2018
2
In vivo efficacy of the AKT inhibitor ARQ 092 in Noonan Syndrome with multiple lentigines-associated hypertrophic cardiomyopathy. ( 28582432 )
2017
3
Heterozygous deletion of AKT1 rescues cardiac contractility, but not hypertrophy, in a mouse model of Noonan Syndrome with Multiple Lentigines. ( 28911943 )
2017
4
Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11. ( 28483241 )
2017
5
Noonan syndrome with multiple lentigines with PTPN11 (T468M) gene mutation accompanied with solitary granular cell tumor. ( 28681392 )
2017
6
Hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26952712 )
2016
7
Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines. ( 27348588 )
2016
8
Multiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines. ( 27238887 )
2016
9
Elevated calcium transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan Syndrome with Multiple Lentigines. ( 25724491 )
2015
10
Rapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: Palliative treatment with a rapamycin analog. ( 25708222 )
2015
11
A novel heterozygous MAP2K1 mutation in a patient with Noonan syndrome with multiple lentigines. ( 25423878 )
2015
12
Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26337637 )
2015

Variations for Noonan Syndrome with Multiple Lentigines

ClinVar genetic disease variations for Noonan Syndrome with Multiple Lentigines:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 PTPN11 NM_002834.4(PTPN11): c.1403C> T (p.Thr468Met) single nucleotide variant 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 PTPN11 NM_002834.4(PTPN11): c.1529A> C (p.Gln510Pro) single nucleotide variant Pathogenic rs121918470 GRCh37 Chromosome 12, 112926909: 112926909
4 RAF1 NM_002880.3(RAF1): c.770C> T (p.Ser257Leu) single nucleotide variant Pathogenic rs80338796 GRCh37 Chromosome 3, 12645699: 12645699
5 RAF1 NM_002880.3(RAF1): c.1837C> G (p.Leu613Val) single nucleotide variant Pathogenic rs80338797 GRCh37 Chromosome 3, 12626123: 12626123
6 RAF1 NM_002880.3(RAF1): c.1456G> A (p.Asp486Asn) single nucleotide variant Pathogenic rs80338798 GRCh37 Chromosome 3, 12627260: 12627260
7 RAF1 NM_002880.3(RAF1): c.1472C> T (p.Thr491Ile) single nucleotide variant Pathogenic rs80338799 GRCh37 Chromosome 3, 12627244: 12627244
8 BRAF NM_004333.4(BRAF): c.721A> C (p.Thr241Pro) single nucleotide variant Pathogenic/Likely pathogenic rs387906661 GRCh37 Chromosome 7, 140501351: 140501351
9 BRAF NM_004333.4(BRAF): c.735A> T (p.Leu245Phe) single nucleotide variant Pathogenic/Likely pathogenic rs397507466 GRCh37 Chromosome 7, 140501337: 140501337
10 PTPN11 NM_002834.4(PTPN11): c.1381G> T (p.Ala461Ser) single nucleotide variant Pathogenic rs121918468 GRCh37 Chromosome 12, 112926248: 112926248
11 PTPN11 NM_002834.4(PTPN11): c.1517A> C (p.Gln506Pro) single nucleotide variant Pathogenic rs397507548 GRCh37 Chromosome 12, 112926897: 112926897
12 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 47)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.59 BRAF PTPN11 RAF1
2
Show member pathways
12.46 BRAF PTPN11 RAF1
3
Show member pathways
12.4 BRAF PTPN11 RAF1
4
Show member pathways
12.38 BRAF PTPN11 RAF1
5
Show member pathways
12.13 BRAF PTPN11 RAF1
6
Show member pathways
12.06 BRAF PTPN11 RAF1
7
Show member pathways
11.97 BRAF PTPN11 RAF1
8
Show member pathways
11.92 BRAF PTPN11 RAF1
9 11.86 PTPN11 RAF1
10
Show member pathways
11.84 BRAF RAF1
11
Show member pathways
11.83 BRAF RAF1
12
Show member pathways
11.82 PTPN11 RAF1
13 11.8 BRAF RAF1
14
Show member pathways
11.78 BRAF RAF1
15
Show member pathways
11.75 BRAF PTPN11 RAF1
16 11.74 BRAF PTPN11 RAF1
17 11.73 BRAF RAF1
18 11.72 BRAF RAF1
19
Show member pathways
11.71 PTPN11 RAF1
20 11.7 BRAF RAF1
21 11.68 BRAF RAF1
22
Show member pathways
11.65 PTPN11 RAF1
23 11.64 BRAF RAF1
24 11.62 BRAF RAF1
25 11.61 PTPN11 RAF1
26
Show member pathways
11.57 BRAF RAF1
27 11.55 BRAF PTPN11 RAF1
28 11.54 BRAF RAF1
29 11.5 BRAF RAF1
30 11.47 BRAF RAF1
31
Show member pathways
11.44 BRAF RAF1
32
Show member pathways
11.41 BRAF RAF1
33
Show member pathways
11.4 BRAF RAF1
34 11.4 BRAF RAF1
35 11.39 BRAF RAF1
36 11.33 BRAF RAF1
37
Show member pathways
11.32 BRAF PTPN11 RAF1
38 11.29 BRAF RAF1
39 11.21 PTPN11 RAF1
40 11.2 PTPN11 RAF1
41 11.17 BRAF RAF1
42 11.05 PTPN11 RAF1
43
Show member pathways
11.02 BRAF RAF1
44
Show member pathways
10.99 PTPN11 RAF1
45 10.94 PTPN11 RAF1
46 10.89 BRAF RAF1
47 10.85 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)
# 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:

# Name GO ID Score Top Affiliating Genes
1 signal transducer activity, downstream of receptor GO:0005057 9.26 BRAF RAF1
2 MAP kinase kinase kinase activity GO:0004709 9.16 BRAF RAF1
3 small GTPase binding GO:0031267 8.96 BRAF RAF1
4 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
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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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