MCID: NNN022
MIFTS: 25

Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia

Categories: Genetic diseases, Cancer diseases, Neuronal diseases, Cardiovascular diseases, Fetal diseases, Rare diseases

Aliases & Classifications for Noonan Syndrome-Like Disorder with or Without Juvenile...

MalaCards integrated aliases for Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia:

Name: Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia 53 71 28 69
Cbl Syndrome 53 55
Nsll 53 71
Noonan Syndrome-Like Disorder with Juvenile Myelomonocytic Leukemia 55
Noonan Syndrome-Like Disorder with Jmml 55
Cbl Mutation-Associated Syndrome 53

Characteristics:

Orphanet epidemiological data:

55

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype


HPO:

31
noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia:
Onset and clinical course phenotypic variability
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Noonan Syndrome-Like Disorder with or Without Juvenile...

OMIM : 53 Noonan syndrome-like disorder is a developmental disorder resembling Noonan syndrome (NS1; 163950) and characterized by facial dysmorphism, a wide spectrum of cardiac disease, reduced growth, variable cognitive deficits, and ectodermal and musculoskeletal anomalies. There is extensive phenotypic heterogeneity and variable expressivity (summary by Martinelli et al., 2010). Patients with heterozygous germline CBL mutations have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia (JMML; 607785), as also seen in patients with Noonan syndrome (summary by Niemeyer et al., 2010). (613563)

MalaCards based summary : Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia, also known as cbl syndrome, is related to splenomegaly, and has symptoms including joint laxity, hypertelorism and low-set ears. An important gene associated with Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia is CBL (Cbl Proto-Oncogene). Affiliated tissues include heart.

UniProtKB/Swiss-Prot : 71 Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia: A syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects. Some have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia.

Related Diseases for Noonan Syndrome-Like Disorder with or Without Juvenile...

Diseases related to Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 splenomegaly 9.7

Symptoms & Phenotypes for Noonan Syndrome-Like Disorder with or Without Juvenile...

Symptoms via clinical synopsis from OMIM:

53
Skeletal:
joint laxity

HeadAndNeckEars:
low-set ears
large ears

ChestExternalFeatures:
pectus excavatum

HeadAndNeckNose:
depressed nasal bridge

SkeletalLimbs:
cubitus valgus

HeadAndNeckMouth:
thick lips

CardiovascularHeart:
aortic stenosis
congenital heart defects
mitral insufficiency

GrowthHeight:
short stature (in some patients)

SkinNailsHairHair:
thin hair

CardiovascularVascular:
chylothorax (in some patients)

Neoplasia:
increased susceptibility to juvenile myelomonocytic leukemia

HeadAndNeckEyes:
hypertelorism
ptosis
downslanting palpebral fissures

HeadAndNeckNeck:
short neck
webbed neck

HeadAndNeckFace:
frontal bossing
long philtrum
triangular face

GenitourinaryInternalGenitaliaMale:
cryptorchidism

MuscleSoftTissue:
hypotonia

ChestBreasts:
widely spaced nipples

NeurologicCentralNervousSystem:
language delay
delayed psychomotor development, mild

SkinNailsHairSkin:
cafe-au-lait spots
lymphedema (in some patients)

PrenatalManifestationsAmnioticFluid:
polyhydramnios (in some patients)
fetal hydrops (in some patients)

RespiratoryLung:
pleural effusions due to chylothorax (in some patients)


Clinical features from OMIM:

613563

Human phenotypes related to Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia:

31 (show all 35)
# Description HPO Frequency HPO Source Accession
1 joint laxity 31 HP:0001388
2 hypertelorism 31 HP:0000316
3 low-set ears 31 HP:0000369
4 short neck 31 HP:0000470
5 pectus excavatum 31 HP:0000767
6 frontal bossing 31 HP:0002007
7 ptosis 31 HP:0000508
8 macrotia 31 HP:0000400
9 global developmental delay 31 HP:0001263
10 depressed nasal bridge 31 HP:0005280
11 delayed speech and language development 31 HP:0000750
12 thick vermilion border 31 HP:0012471
13 short stature 31 occasional (7.5%) HP:0004322
14 long philtrum 31 HP:0000343
15 epicanthus 31 HP:0000286
16 cryptorchidism 31 HP:0000028
17 lymphedema 31 occasional (7.5%) HP:0001004
18 cubitus valgus 31 HP:0002967
19 wide intermamillary distance 31 HP:0006610
20 webbed neck 31 HP:0000465
21 bicuspid aortic valve 31 HP:0001647
22 mitral regurgitation 31 HP:0001653
23 joint hypermobility 31 HP:0001382
24 downslanted palpebral fissures 31 HP:0000494
25 polyhydramnios 31 occasional (7.5%) HP:0001561
26 deep philtrum 31 HP:0002002
27 fine hair 31 HP:0002213
28 triangular face 31 HP:0000325
29 sparse hair 31 HP:0008070
30 aortic valve stenosis 31 HP:0001650
31 cafe-au-lait spot 31 HP:0000957
32 chylothorax 31 occasional (7.5%) HP:0010310
33 generalized hypotonia 31 HP:0001290
34 posteriorly rotated ears 31 HP:0000358
35 juvenile myelomonocytic leukemia 31 HP:0012209

Drugs & Therapeutics for Noonan Syndrome-Like Disorder with or Without Juvenile...

Search Clinical Trials , NIH Clinical Center for Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia

Genetic Tests for Noonan Syndrome-Like Disorder with or Without Juvenile...

Genetic tests related to Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia:

# Genetic test Affiliating Genes
1 Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia 28 CBL

Anatomical Context for Noonan Syndrome-Like Disorder with or Without Juvenile...

MalaCards organs/tissues related to Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia:

38
Heart

Publications for Noonan Syndrome-Like Disorder with or Without Juvenile...

Articles related to Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia:

# Title Authors Year
1
A case of splenomegaly in CBL syndrome. ( 28414188 )
2017

Variations for Noonan Syndrome-Like Disorder with or Without Juvenile...

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia:

71
# Symbol AA change Variation ID SNP ID
1 CBL p.Gln367Pro VAR_064332 rs267606704
2 CBL p.Lys382Glu VAR_064333 rs267606705
3 CBL p.Asp390Tyr VAR_064334 rs267606707
4 CBL p.Arg420Gln VAR_064335 rs267606708

ClinVar genetic disease variations for Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia:

6 (show all 15)
# Gene Variation Type Significance SNP ID Assembly Location
1 PTPN11 NM_002834.4(PTPN11): c.836A> G (p.Tyr279Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121918456 GRCh37 Chromosome 12, 112910827: 112910827
2 CBL NM_005188.3(CBL): c.1100A> C (p.Gln367Pro) single nucleotide variant Pathogenic rs267606704 GRCh37 Chromosome 11, 119148880: 119148880
3 CBL NM_005188.3(CBL): c.1144A> G (p.Lys382Glu) single nucleotide variant Pathogenic rs267606705 GRCh37 Chromosome 11, 119148924: 119148924
4 CBL NM_005188.3(CBL): c.1168G> T (p.Asp390Tyr) single nucleotide variant Pathogenic rs267606707 GRCh37 Chromosome 11, 119148948: 119148948
5 CBL NM_005188.3(CBL): c.1259G> A (p.Arg420Gln) single nucleotide variant Pathogenic rs267606708 GRCh37 Chromosome 11, 119149251: 119149251
6 CBL NM_005188.3(CBL): c.1111T> C (p.Tyr371His) single nucleotide variant Pathogenic/Likely pathogenic rs267606706 GRCh37 Chromosome 11, 119148891: 119148891
7 CBL CBL, IVS8AS, A-G, -2 single nucleotide variant Pathogenic
8 CBL NM_005188.3(CBL): c.1150T> C (p.Cys384Arg) single nucleotide variant Pathogenic/Likely pathogenic rs387906664 GRCh37 Chromosome 11, 119148930: 119148930
9 CBL NM_005188.3(CBL): c.1186T> C (p.Cys396Arg) single nucleotide variant Pathogenic rs387906665 GRCh37 Chromosome 11, 119148966: 119148966
10 CBL NM_005188.3(CBL): c.1112A> G (p.Tyr371Cys) single nucleotide variant Pathogenic rs387906666 GRCh37 Chromosome 11, 119148892: 119148892
11 CBL NM_005188.3(CBL): c.1096-1G> C single nucleotide variant Pathogenic rs397517076 GRCh37 Chromosome 11, 119148875: 119148875
12 CBL NM_005188.3(CBL): c.1096-4_1096-1delAAAG deletion Pathogenic/Likely pathogenic rs397517077 GRCh37 Chromosome 11, 119148872: 119148875
13 CBL NM_005188.3(CBL): c.1099C> A (p.Gln367Lys) single nucleotide variant Likely pathogenic rs727504504 GRCh38 Chromosome 11, 119278169: 119278169
14 CBL NM_005188.3(CBL): c.1228-2A> G single nucleotide variant Pathogenic/Likely pathogenic rs727504426 GRCh37 Chromosome 11, 119149218: 119149218
15 CBL NM_005188.3(CBL): c.1096-1G> T single nucleotide variant Pathogenic rs397517076 GRCh37 Chromosome 11, 119148875: 119148875

Expression for Noonan Syndrome-Like Disorder with or Without Juvenile...

Search GEO for disease gene expression data for Noonan Syndrome-Like Disorder with or Without Juvenile Myelomonocytic Leukemia.

Pathways for Noonan Syndrome-Like Disorder with or Without Juvenile...

GO Terms for Noonan Syndrome-Like Disorder with or Without Juvenile...

Sources for Noonan Syndrome-Like Disorder with or Without Juvenile...

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