MCID: NNN021
MIFTS: 28

Noonan Syndrome 8

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Cardiovascular diseases, Nephrological diseases, Reproductive diseases, Skin diseases, Endocrine diseases, Fetal diseases

Aliases & Classifications for Noonan Syndrome 8

Summaries for Noonan Syndrome 8

UniProtKB/Swiss-Prot : 75 Noonan syndrome 8: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.

MalaCards based summary : Noonan Syndrome 8, is also known as ns8. An important gene associated with Noonan Syndrome 8 is RIT1 (Ras Like Without CAAX 1). The drugs Zidovudine and Miglustat have been mentioned in the context of this disorder. Affiliated tissues include heart and skin, and related phenotypes are cryptorchidism and epicanthus

OMIM : 57 Noonan syndrome-8 is an autosomal dominant disorder characterized by short stature, distinctive facial features, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. A subset of patients show intellectual disabilities (summary by Aoki et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950). (615355)

Disease Ontology : 12 A Noonan syndrome that has material basis in aused by heterozygous mutation in the RIT1 gene on chromosome 1q22.

Related Diseases for Noonan Syndrome 8

Symptoms & Phenotypes for Noonan Syndrome 8

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
ptosis
downslanting palpebral fissures
epicanthal folds

Head And Neck Neck:
short neck
webbed neck

Growth Height:
short stature

Skin Nails Hair Skin:
hyperkeratosis
hyperelastic skin

Prenatal Manifestations Amniotic Fluid:
polyhydramnios
fetal pleural effusion

Head And Neck Head:
relative macrocephaly

Head And Neck Ears:
low-set ears

Growth Other:
failure to thrive

Cardiovascular Heart:
hypertrophic cardiomyopathy
atrial septal defect
ventricular septal defect
pulmonic stenosis
valvular insufficiency

GenitourinaryInternal GenitaliaMale:
cryptorchidism

Skin Nails Hair Hair:
curly hair

Neurologic Central Nervous System:
intellectual disability (in some patients)


Clinical features from OMIM:

615355

Human phenotypes related to Noonan Syndrome 8:

32 (show all 25)
# Description HPO Frequency HPO Source Accession
1 cryptorchidism 32 very rare (1%) HP:0000028
2 epicanthus 32 HP:0000286
3 hypertelorism 32 HP:0000316
4 low-set ears 32 HP:0000369
5 webbed neck 32 very rare (1%) HP:0000465
6 short neck 32 HP:0000470
7 downslanted palpebral fissures 32 HP:0000494
8 ptosis 32 HP:0000508
9 abnormality of the sternum 32 very rare (1%) HP:0000766
10 hyperpigmentation of the skin 32 very rare (1%) HP:0000953
11 hyperkeratosis 32 HP:0000962
12 hyperextensible skin 32 very rare (1%) HP:0000974
13 intellectual disability 32 very rare (1%) HP:0001249
14 failure to thrive 32 HP:0001508
15 polyhydramnios 32 HP:0001561
16 ventricular septal defect 32 HP:0001629
17 atrial septal defect 32 HP:0001631
18 hypertrophic cardiomyopathy 32 HP:0001639
19 pulmonic stenosis 32 HP:0001642
20 patent ductus arteriosus 32 very rare (1%) HP:0001643
21 left ventricular hypertrophy 32 very rare (1%) HP:0001712
22 curly hair 32 very rare (1%) HP:0002212
23 short stature 32 very rare (1%) HP:0004322
24 relative macrocephaly 32 very rare (1%) HP:0004482
25 palmoplantar cutis laxa 32 very rare (1%) HP:0007517

Drugs & Therapeutics for Noonan Syndrome 8

Drugs for Noonan Syndrome 8 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Zidovudine Approved Phase 2 30516-87-1 35370
2
Miglustat Approved Phase 2 72599-27-0 51634
3
1-Deoxynojirimycin Experimental Phase 2 19130-96-2 1374
4 Reverse Transcriptase Inhibitors Phase 2
5 Glycoside Hydrolase Inhibitors Phase 2
6 Nucleic Acid Synthesis Inhibitors Phase 2
7 Hypoglycemic Agents Phase 2
8 Anti-Infective Agents Phase 2
9 Anti-HIV Agents Phase 2
10 Anti-Retroviral Agents Phase 2
11 Antimetabolites Phase 2
12 Antiviral Agents Phase 2
13 Cardiac Glycosides Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phase II Study of the Safety and Surrogate Marker Efficacy of Butyldeoxynojirimycin (SC-48334) and AZT in Symptomatic HIV-1 Infected Patients With 200 - 500 CD4+ Cells/mm3. (NOTE: Asymptomatic HIV-1 Infected Patients Also Eligible) Completed NCT00002079 Phase 2 Butyldeoxynojirimycin;Zidovudine
2 Initial Phase II Efficacy and Safety Study of SC-48334 Administered in Combination With Low-Dose Zidovudine (AZT) to Symptomatic HIV-1 Infected Patients With = or > 200 to = or < 500 CD4+ Cells/mm3 Completed NCT00001993 Phase 2 Butyldeoxynojirimycin;Zidovudine

Search NIH Clinical Center for Noonan Syndrome 8

Genetic Tests for Noonan Syndrome 8

Genetic tests related to Noonan Syndrome 8:

# Genetic test Affiliating Genes
1 Noonan Syndrome 8 29 RIT1

Anatomical Context for Noonan Syndrome 8

MalaCards organs/tissues related to Noonan Syndrome 8:

41
Heart, Skin

Publications for Noonan Syndrome 8

Variations for Noonan Syndrome 8

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome 8:

75
# Symbol AA change Variation ID SNP ID
1 RIT1 p.Ala57Gly VAR_070150 rs672601334
2 RIT1 p.Glu81Gly VAR_070151 rs869025193
3 RIT1 p.Phe82Leu VAR_070152 rs730881014
4 RIT1 p.Met90Ile VAR_070156 rs483352822
5 RIT1 p.Gly95Ala VAR_070157 rs672601335

ClinVar genetic disease variations for Noonan Syndrome 8:

6
(show all 37)
# Gene Variation Type Significance SNP ID Assembly Location
1 RIT1 NM_006912.5(RIT1): c.170C> G (p.Ala57Gly) single nucleotide variant Pathogenic rs672601334 GRCh37 Chromosome 1, 155874589: 155874589
2 RIT1 NM_006912.5(RIT1): c.170C> G (p.Ala57Gly) single nucleotide variant Pathogenic rs672601334 GRCh38 Chromosome 1, 155904798: 155904798
3 RIT1 NM_006912.5(RIT1): c.284G> C (p.Gly95Ala) single nucleotide variant Pathogenic rs672601335 GRCh37 Chromosome 1, 155874247: 155874247
4 RIT1 NM_006912.5(RIT1): c.284G> C (p.Gly95Ala) single nucleotide variant Pathogenic rs672601335 GRCh38 Chromosome 1, 155904456: 155904456
5 RIT1 NM_006912.5(RIT1): c.270G> A (p.Met90Ile) single nucleotide variant Pathogenic rs483352822 GRCh38 Chromosome 1, 155904470: 155904470
6 RIT1 NM_006912.5(RIT1): c.270G> A (p.Met90Ile) single nucleotide variant Pathogenic rs483352822 GRCh37 Chromosome 1, 155874261: 155874261
7 RIT1 NM_006912.5(RIT1): c.246T> G (p.Phe82Leu) single nucleotide variant Pathogenic rs730881014 GRCh38 Chromosome 1, 155904494: 155904494
8 RIT1 NM_006912.5(RIT1): c.246T> G (p.Phe82Leu) single nucleotide variant Pathogenic rs730881014 GRCh37 Chromosome 1, 155874285: 155874285
9 RIT1 NM_006912.5(RIT1): c.244T> G (p.Phe82Val) single nucleotide variant Pathogenic rs869025194 GRCh38 Chromosome 1, 155904496: 155904496
10 RIT1 NM_006912.5(RIT1): c.244T> G (p.Phe82Val) single nucleotide variant Pathogenic rs869025194 GRCh37 Chromosome 1, 155874287: 155874287
11 RIT1 NM_006912.5(RIT1): c.244T> A (p.Phe82Ile) single nucleotide variant Uncertain significance rs869025194 GRCh38 Chromosome 1, 155904496: 155904496
12 RIT1 NM_006912.5(RIT1): c.244T> A (p.Phe82Ile) single nucleotide variant Uncertain significance rs869025194 GRCh37 Chromosome 1, 155874287: 155874287
13 RIT1 NM_006912.5(RIT1): c.242A> G (p.Glu81Gly) single nucleotide variant Pathogenic rs869025193 GRCh38 Chromosome 1, 155904498: 155904498
14 RIT1 NM_006912.5(RIT1): c.242A> G (p.Glu81Gly) single nucleotide variant Pathogenic rs869025193 GRCh37 Chromosome 1, 155874289: 155874289
15 RIT1 NM_006912.5(RIT1): c.229G> A (p.Ala77Thr) single nucleotide variant Pathogenic/Likely pathogenic rs869025191 GRCh38 Chromosome 1, 155904739: 155904739
16 RIT1 NM_006912.5(RIT1): c.229G> A (p.Ala77Thr) single nucleotide variant Pathogenic/Likely pathogenic rs869025191 GRCh37 Chromosome 1, 155874530: 155874530
17 RIT1 NM_006912.5(RIT1): c.104G> C (p.Ser35Thr) single nucleotide variant Pathogenic rs869025189 GRCh38 Chromosome 1, 155910658: 155910658
18 RIT1 NM_006912.5(RIT1): c.104G> C (p.Ser35Thr) single nucleotide variant Pathogenic rs869025189 GRCh37 Chromosome 1, 155880449: 155880449
19 RIT1 NM_006912.5(RIT1): c.270G> C (p.Met90Ile) single nucleotide variant Pathogenic rs483352822 GRCh37 Chromosome 1, 155874261: 155874261
20 RIT1 NM_006912.5(RIT1): c.270G> C (p.Met90Ile) single nucleotide variant Pathogenic rs483352822 GRCh38 Chromosome 1, 155904470: 155904470
21 RIT1 NM_001256821.1(RIT1): c.426C> T (p.Asp142=) single nucleotide variant Benign rs34831194 GRCh37 Chromosome 1, 155874156: 155874156
22 RIT1 NM_001256821.1(RIT1): c.426C> T (p.Asp142=) single nucleotide variant Benign rs34831194 GRCh38 Chromosome 1, 155904365: 155904365
23 RIT1 NM_006912.5(RIT1): c.67A> C (p.Lys23Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs869312687 GRCh37 Chromosome 1, 155880486: 155880486
24 RIT1 NM_006912.5(RIT1): c.67A> C (p.Lys23Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs869312687 GRCh38 Chromosome 1, 155910695: 155910695
25 RIT1 NM_006912.5(RIT1): c.229G> C (p.Ala77Pro) single nucleotide variant Pathogenic/Likely pathogenic rs869025191 GRCh38 Chromosome 1, 155904739: 155904739
26 RIT1 NM_006912.5(RIT1): c.229G> C (p.Ala77Pro) single nucleotide variant Pathogenic/Likely pathogenic rs869025191 GRCh37 Chromosome 1, 155874530: 155874530
27 RIT1 NM_006912.5(RIT1): c.246T> A (p.Phe82Leu) single nucleotide variant Pathogenic rs730881014 GRCh38 Chromosome 1, 155904494: 155904494
28 RIT1 NM_006912.5(RIT1): c.246T> A (p.Phe82Leu) single nucleotide variant Pathogenic rs730881014 GRCh37 Chromosome 1, 155874285: 155874285
29 RIT1 NM_006912.5(RIT1): c.334C> T (p.Arg112Cys) single nucleotide variant Uncertain significance rs375724784 GRCh37 Chromosome 1, 155874197: 155874197
30 RIT1 NM_006912.5(RIT1): c.334C> T (p.Arg112Cys) single nucleotide variant Uncertain significance rs375724784 GRCh38 Chromosome 1, 155904406: 155904406
31 RIT1 NC_000001.10: g.(?_155880221)_(156109650_?)del deletion Uncertain significance GRCh37 Chromosome 1, 155880221: 156109650
32 RIT1 NM_006912.5(RIT1): c.237+10C> A single nucleotide variant Benign/Likely benign rs367785615 GRCh37 Chromosome 1, 155874512: 155874512
33 RIT1 NM_006912.5(RIT1): c.237+10C> A single nucleotide variant Benign/Likely benign rs367785615 GRCh38 Chromosome 1, 155904721: 155904721
34 RIT1 NM_006912.5(RIT1): c.644_647delAAGA (p.Lys215Ilefs) deletion Conflicting interpretations of pathogenicity rs766063111 GRCh37 Chromosome 1, 155870192: 155870195
35 RIT1 NM_006912.5(RIT1): c.644_647delAAGA (p.Lys215Ilefs) deletion Conflicting interpretations of pathogenicity rs766063111 GRCh38 Chromosome 1, 155900401: 155900404
36 RIT1 NM_006912.5(RIT1): c.393T> C (p.Leu131=) single nucleotide variant Likely benign rs34974790 GRCh37 Chromosome 1, 155874138: 155874138
37 RIT1 NM_006912.5(RIT1): c.393T> C (p.Leu131=) single nucleotide variant Likely benign rs34974790 GRCh38 Chromosome 1, 155904347: 155904347

Expression for Noonan Syndrome 8

Search GEO for disease gene expression data for Noonan Syndrome 8.

Pathways for Noonan Syndrome 8

GO Terms for Noonan Syndrome 8

Sources for Noonan Syndrome 8

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