NS
MCID: NTH001
MIFTS: 63

Netherton Syndrome (NS) malady

Eye diseases, Skin diseases categories

Summaries for Netherton Syndrome

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21Genetics Home Reference, 42NIH Rare Diseases, 63Wikipedia, 46OMIM, 32MalaCards
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Genetics Home Reference:21 Netherton syndrome is a disorder that affects the skin, hair, and immune system. Newborns with Netherton syndrome have skin that is red and scaly (ichthyosiform erythroderma), and the skin may leak fluid. Some affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life. Because newborns with this disorder are missing the protection provided by normal skin, they are at risk of becoming dehydrated and developing infections in the skin or throughout the body (sepsis), which can be life-threatening. Affected babies may also fail to grow and gain weight at the expected rate (failure to thrive). The health of older children and adults with Netherton syndrome usually improves, although they often remain underweight and of short stature.

MalaCards: Netherton Syndrome, also known as netherton disease, is related to dermatitis and atopic dermatitis, and has symptoms including hypotrichosis/atrichia/atrichiasis/scalp hairlessness, megaureter/hydronephrosis/pyeloureteral junction syndrome and asthma/bronchospasm. An important gene associated with Netherton Syndrome is SPINK5 (serine peptidase inhibitor, Kazal type 5). The compounds 4-nitroanilide and elastatinal have been mentioned in the context of this disorder. Affiliated tissues include skin, b cells and eye, and related mouse phenotypes are immune system and integument.

NIH Rare Diseases:42 Netherton syndrome is a type of ichthyosis. symptoms vary but commonly include inflamed, red, scaly skin, short, brittle, lustreless hair, and a predisposition to allergy problems (e.g., to nuts, hay fever, and asthma).  symptoms may be mild or severe and tend to present in infancy. failure to thrive and recurrent infection are possible complications in infants with this syndrome. netherton syndrome is caused by mutations in the spink5 gene. it is inherited in an autosomal recessive fashion. last updated: 9/14/2011

Wikipedia:63 Netherton syndrome is a severe, autosomal recessive form of ichthyosis associated with mutations in the... more...

Description from OMIM:46 256500,310465

Aliases & Classifications for Netherton Syndrome

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8Disease Ontology, 9diseasecard, 42NIH Rare Diseases, 21Genetics Home Reference, 46OMIM, 10DISEASES, 44Novoseek, 48Orphanet, 60UMLS, 20GeneTests, 22GTR, 34MeSH, 57SNOMED-CT via Orphanet, 26ICD10 via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Anatomical: Eye diseases, Skin diseases


Characteristics (Orphanet epidemiological data):

48
netherton syndrome:
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000; Age of onset: Neonatal/infancy; Age of death: Normal


Aliases & Descriptions:

netherton syndrome 8 9 42 21 46 10 44 48
netherton disease 42 20 22 21
n syndrome 46 10 60
ichthyosis linearis circumflexa 21 60
bamboo hair syndrome 21 48
neth 42 21
ns 21 48
ichthyosiform erythroderma with hypotrichosis and hyper-ige 21
comèl-netherton syndrome 48
comel-netherton syndrome 21
ilc 21


External Ids:

Disease Ontology8 DOID:0050474
OMIM46 256500
MeSH34 D056770
SNOMED-CT via Orphanet57 312514006, 22486004
ICD10 via Orphanet26 Q80.3

Related Diseases for Netherton Syndrome

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17GeneCards, 18GeneDecks
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Diseases related to Netherton Syndrome via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 75)
idRelated DiseaseScoreTop Affiliating Genes
1dermatitis30.3FLG, DSC1, TSLP, IGHE, DSG1
2atopic dermatitis30.3KLK7, FLG, IGHE, CDSN, SPINK5, TSLP
3congenital ichthyosiform erythroderma30.2SPINK5, TGM1
4skin disease30.2KLK7, TGM3, TGM1, SPINK5, CDSN, IGHE
5pancreatitis30.0ELANE, SPINK1
6ichthyosis vulgaris30.0FLG, TGM1
7acute pancreatitis30.0ELANE, SPINK1
8psoriasis30.0KLK7, PI3, FLG, CDSN, SPINK5, ELANE
9ichthyosis linearis circumflexa10.7
10influenza10.5
11n syndrome10.4
12hair disease10.4
13dwarfism10.4
14noonan-like/multiple giant cell lesion syndrome10.3
15avian influenza10.2
16exfoliation syndrome10.2
17adult syndrome10.2
18noonan syndrome10.1
19nephrotic syndrome10.1
20pseudohypoparathyroidism10.1
21noonan syndrome 110.1
22molluscum contagiosum10.0
23acrodermatitis10.0
24rickets10.0
25hypertension10.0
26hypothyroidism10.0
27melanoma10.0
28skin melanoma10.0
29autosomal recessive congenital ichthyosis10.0TGM1
30sinusitis10.0IGHE
31eosinophilic esophagitis10.0TSLP
32rhinitis10.0IGHE
33extrinsic allergic alveolitis10.0IGHE, PI3
34eczema herpeticum10.0IGHE, TSLP
35harlequin type ichthyosis10.0FLG, TGM1
36alcoholic pancreatitis10.0ELANE, SPINK1
37contact dermatitis10.0IGHE, FLG
38arthritis10.0FLG, CTSG
39keratoderma10.0DSG1, TGM1
40bronchiectasis10.0CTSG, IGHE, ELANE
41keratosis10.0FLG
42subcorneal pustular dermatosis10.0DSC1, DSG1
43x-linked ichthyosis10.0FLG
44adult respiratory distress syndrome10.0CTSG, ELANE
45pulmonary disease, chronic obstructive10.0CTSG, PI3, ELANE
46bullous pemphigoid10.0FLG, DSG1, IGHE
47allergic rhinitis10.0FLG, IGHE, TSLP
48atopy10.0TSLP, SPINK5, IGHE, FLG
49pemphigus10.0DSG1, DSC1
50allergic asthma10.0TSLP, IGHE, FLG

Graphical network of the top 20 diseases related to Netherton Syndrome:



Diseases related to netherton syndrome

Clinical Features for Netherton Syndrome

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Sources:
46OMIM, 48Orphanet
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Clinical features from OMIM:

256500,310465

Clinical synopsis from OMIM:

256500

Symptoms:

48 (show all 28)
  • hypotrichosis/atrichia/atrichiasis/scalp hairlessness
  • megaureter/hydronephrosis/pyeloureteral junction syndrome
  • asthma/bronchospasm
  • fine hair
  • acanthosis nigricans
  • eczema
  • absent/decreased/thin eyebrows
  • hair and scalp anomalies
  • severe allergic reaction/atopy
  • brittle hair/distrix/trichorrhexis
  • agammaglobulinemia/hypogammaglobulinemia/b-cell deficiency
  • urticaria
  • seizures/epilepsy/absences/spasms/status epilepticus
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • repeat respiratory infections
  • malabsorption/chronic diarrhea/steatorrhea
  • ichthyosis/ichthyosiform dermatitis
  • short stature/dwarfism/nanism
  • aminoacid metabolism anomalies/aminoaciduria
  • dehydration/hydroelectrolytic loss
  • emphysema
  • immunodeficiency/increased susceptibility to infections/recurrent infections
  • ectopic/horseshoe/fused kidneys
  • dry/squaly skin/exfoliation
  • cutaneous rash
  • erythema/erythematous lesions/erythroderma/polymorphous erythema
  • irregular/in bands/reticular skin hyperpigmentation
  • autosomal recessive inheritance

Drugs & Therapeutics for Netherton Syndrome

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Sources:
5CenterWatch, 41NIH Clinical Center, 6ClinicalTrials, 60UMLS, 40NDF-RT
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Approved drugs:

Search CenterWatch for Netherton Syndrome

Drug clinical trials:

Search ClinicalTrials for Netherton Syndrome

Search NIH Clinical Center for Netherton Syndrome

Search CenterWatch for Netherton Syndrome

Genetic Tests for Netherton Syndrome

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20GeneTests, 22GTR
See all sources

Genetic tests related to Netherton Syndrome:

id Genetic test Affiliating Genes
1 Netherton Syndrome20 22 SPINK5

Anatomical Context for Netherton Syndrome

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Sources:
32MalaCards
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MalaCards organs/tissues related to Netherton Syndrome:

32
Skin, B cells, Eye, Kidney, Testes, Thymus

Animal Models for Netherton Syndrome or affiliated genes

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36MGI
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MGI Mouse Phenotypes related to Netherton Syndrome:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053878.2FLG, DSC1, IGHE, CDSN, SPINK1, SPINK5
2MP:00107718.0TGM3, FLG, DSC1, CDSN, SPINK1, SPINK5

Publications for Netherton Syndrome

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Sources:
50PubMed
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Articles related to Netherton Syndrome:

(show top 50)    (show all 106)
idTitleAuthorsYear
1
Netherton syndrome: skin inflammation and allergy by loss of protease inhibition. (23344365)
2013
2
Netherton syndrome and its multifaceted defective protein LEKTI. (23407075)
2013
3
Netherton syndrome showing a large clinical overlap with generalized inflammatory peeling skin syndrome. (22562784)
2012
4
A new SPINK5 mutation in a patient with Netherton syndrome: a case report. (21692842)
2012
5
A synonymous mutation in SPINK5 exon 11 causes Netherton syndrome by altering exonic splicing regulatory elements. (22377713)
2012
6
Prenatal diagnosis of Comel-Netherton syndrome with PGD, case report and review article. (21573681)
2011
7
Infliximab infusions for Netherton syndrome: sustained clinical improvement correlates with a reduction of thymic stromal lymphopoietin levels in the skin. (21654837)
2011
8
Netherton syndrome: A rare genodermatosis. (23130216)
2011
9
Ex-vivo gene therapy restores LEKTI activity and corrects the architecture of Netherton syndrome-derived skin grafts. (20877344)
2011
10
Par2 inactivation inhibits early production of TSLP, but not cutaneous inflammation, in Netherton syndrome adult mouse model. (20703245)
2010
11
The safety and efficacy of pimecrolimus, 1%, cream for the treatment of Netherton syndrome: results from an exploratory study. (20083693)
2010
12
Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing. (20179351)
2010
13
Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome. (20657595)
2010
14
Netherton syndrome: dental considerations. (19953815)
2009
15
ComA"l-Netherton syndrome defined as primary immunodeficiency. (19683336)
2009
16
Hair shaft videodermoscopy in netherton syndrome. (19706096)
2009
17
Hypothyroidism in Netherton syndrome. (18304180)
2008
18
Correlation between SPINK5 gene mutations and clinical manifestations in Netherton syndrome patients. (17989726)
2008
19
Netherton syndrome and trichorrhexis invaginata--a novel diagnostic approach. (18429812)
2008
20
Early skeletal signs in Netherton syndrome. (17156006)
2006
21
Netherton syndrome: a case report and review of the literature. (16796630)
2006
22
SPINK5, the defective gene in netherton syndrome, encodes multiple LEKTI isoforms derived from alternative pre-mRNA processing. (16374478)
2006
23
Serine protease activity and residual LEKTI expression determine phenotype in Netherton syndrome. (16601670)
2006
24
Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsin-like hyperactivity in Netherton syndrome. (16628198)
2006
25
Characterization and expression analysis of the Spink5 gene, the mouse ortholog of the defective gene in Netherton syndrome. (15780751)
2005
26
Comel-Netherton syndrome in brothers and expression of cytokeratins. (15793546)
2005
27
Netherton syndrome: a type of infantile erythroderma with failure to thrive, immune deficiency, rickets. Report of 3 cases]. (15935629)
2005
28
Lethal, neonatal ichthyosis with increased proteolytic processing of filaggrin in a mouse model of Netherton syndrome. (15590704)
2005
29
Netherton syndrome with extensive skin peeling and failure to thrive due to a homozygous frameshift mutation in SPINK5. (15942217)
2005
30
Netherton syndrome: report of two Taiwanese siblings with staphylococcal scalded skin syndrome and mutation of SPINK5. (15656819)
2005
31
Netherton syndrome in two Japanese siblings with a novel mutation in the SPINK5 gene: immunohistochemical studies of LEKTI and other epidermal molecules. (16225619)
2005
32
UVA1 phototherapy of Netherton syndrome. (15040483)
2004
33
LEKTI demonstrable by immunohistochemistry of the skin: a potential diagnostic skin test for Netherton syndrome. (15606522)
2004
34
Deleterious mutations in SPINK5 in a patient with congenital ichthyosiform erythroderma: molecular testing as a helpful diagnostic tool for Netherton syndrome. (15347338)
2004
35
A compound heterozygous mutation of the SPINK5 gene in a Taiwanese boy with Netherton syndrome. (12923596)
2003
36
LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome. (12915442)
2003
37
Netherton syndrome associated with idiopathic congenital hemihypertrophy. (12220283)
2002
38
Prenatal diagnosis of a lethal form of Netherton syndrome by SPINK5 mutation analysis. (11857617)
2002
39
Genetic analysis of a severe case of Netherton syndrome and application for prenatal testing. (11952552)
2002
40
Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families. (11841556)
2002
41
Severe hypernatremic dehydration in an infant with Netherton syndrome. (11693786)
2001
42
Clinico-immunological heterogeneity in ComA"l-Netherton syndrome. (11306829)
2001
43
Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome. (11405764)
2001
44
The spectrum of pathogenic mutations in SPINK5 in 19 families with Netherton syndrome: implications for mutation detection and first case of prenatal diagnosis. (11511292)
2001
45
Guess what! ComA"l-Netherton syndrome. (11458927)
2001
46
Comel-Netherton syndrome: evolution of manifestation in a 20-year follow-up and phenotypic overlap with peeling skin syndrome type B. (10954215)
2000
47
Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. (10835624)
2000
48
Selective antibody deficiency to bacterial polysaccharide antigens in patients with Netherton syndrome. (10027993)
1999
49
Comel-Netherton syndrome. A diagnostic challenge. (9349353)
1997
50
Netherton syndrome revisited. (8170853)
1994

Genetic Variations for Netherton Syndrome

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Expression for genes affiliated with Netherton Syndrome

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1BioGPS, 15Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Netherton Syndrome

Search GEO for disease gene expression data for Netherton Syndrome.

Pathways for genes affiliated with Netherton Syndrome

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Compounds for genes affiliated with Netherton Syndrome

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44Novoseek, 2BitterDB, 11DrugBank, 24HMDB, 28IUPHAR, 59Tocris Bioscience, 49PharmGKB
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Compounds related to Netherton Syndrome according to GeneCards/GeneDecks:

(show all 30)
idCompoundScoreTop Affiliating Genes
14-nitroanilide4410.4CTSG, ELANE
2elastatinal4410.4CTSG, ELANE
3tlck4410.4CTRL, ELANE
4saccharin44 211.4CTSG, ELANE
53,4-dichloroisocoumarin44 1111.4ELANE, CTRL
6tannins4410.3ELANE, CTRL
7dithranol4410.3FLG, PI3
8bromelain4410.3IGHE, ELANE
9ovomucoid4410.3IGHE, ELANE
10chymostatin4410.3CTSG, CTRL, ELANE
11(4-aminophenyl)mercuric acetate4410.3ELANE, CTSG
12pmsf4410.3ELANE, CTRL, CTSG
13thermolysin4410.2ELANE, CTSG
14phosphoramidon44 1111.2CTSG, CTRL, ELANE
15diisopropylfluorophosphate4410.2CTSG, CTRL, ELANE
16hocl4410.2CTSG, ELANE
17trypsinogen4410.1SPINK1, ELANE
18epsilon aminocaproic acid4410.1CTSG, ELANE
19aprotinin44 1111.0CTSG, IGHE, ELANE
20aebsf4410.0CTRL, ELANE
21allergens4410.0TSLP, IGHE, FLG
22urea44 11 2412.0FLG, CTRL, CTSG
23sodium dodecylsulfate449.9CTSG, CTRL, PI3, ELANE, TGM1
24histamine44 28 2411.8CTSG, CTRL, PI3, IGHE
25calcipotriol44 59 28 1112.7FLG, TGM1
26cysteine449.5CTSG, CTRL, PI3, FLG, SLC26A2, ELANE
27arginine449.4TGM1, IGHE, FLG, CTRL, CTSG
28serine449.0KLK5, KLK7, CTSG, CTRL, PI3, FLG
29retinoic acid44 249.4TGM1, KLK7, CTSG, CTRL, PI3, FLG
30calcium44 49 11 2411.3KLK7, CTSG, CTRL, PI3, FLG, DSC1

GO Terms for genes affiliated with Netherton Syndrome

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16Gene Ontology
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Cellular components related to Netherton Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1cornified envelopeGO:00153310.0TGM1, CDSN
2epidermal lamellar bodyGO:0972099.8SPINK5, KLK7, KLK5
3desmosomeGO:0300579.2DSC1, DSG1, CDSN
4extracellular regionGO:0055767.8KLK5, KLK7, CTSG, DCD, IGHE, CDSN

Biological processes related to Netherton Syndrome according to GeneCards/GeneDecks:

(show all 8)
idNameGO IDScoreTop Affiliating Genes
1positive regulation of immune responseGO:05077810.1ELANE, CTSG
2cell envelope organizationGO:04316310.0TGM1, TGM3
3negative regulation of growth of symbiont in hostGO:04413010.0CTSG, ELANE
4peptide cross-linkingGO:0181499.9TGM3, TGM1
5epidermis developmentGO:0085449.7CDSN, KLK7, KLK5
6defense response to fungusGO:0508329.6DCD, CTSG
7keratinocyte differentiationGO:0302169.5TGM3, TGM1, CDSN, FLG
8proteolysisGO:0065089.2KLK5, KLK7, CTSG, CTRL, DCD, ELANE

Molecular functions related to Netherton Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1protein-glutamine gamma-glutamyltransferase activityGO:0038109.9TGM3, TGM1
2serine-type endopeptidase activityGO:0042529.4ELANE, CTRL, CTSG, KLK7, KLK5
3peptidase activityGO:0082339.3KLK5, CTSG, DCD, ELANE
4serine-type endopeptidase inhibitor activityGO:0048679.2SPINK5, SPINK9, SPINK1, PI3

Products for genes affiliated with Netherton Syndrome

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  • Antibodies
  • Proteins
  • Lysates
  • Antibodies

Sources for Netherton Syndrome

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
50PubMed
51QIAGEN
57SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet