MCID: NTH001
MIFTS: 57

Netherton Syndrome malady

Genetic diseases, Rare diseases, Eye diseases, Skin diseases categories

Summaries for Netherton Syndrome

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Genetics Home Reference:23 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 based summary: Netherton Syndrome, also known as netherton disease, is related to atopic dermatitis and congenital ichthyosiform erythroderma, and has symptoms including acanthosis nigricans, eczema and urticaria. An important gene associated with Netherton Syndrome is SPINK5 (serine peptidase inhibitor, Kazal type 5), and among its related pathways is Degradation of the extracellular matrix. The compounds tlck and 3,4-dichloroisocoumarin have been mentioned in the context of this disorder. Affiliated tissues include skin, kidney and eye.

NIH Rare Diseases:43 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:65 Netherton syndrome is a severe, autosomal recessive form of ichthyosis associated with mutations in the... more...

Description from OMIM:47 256500

Aliases & Classifications for Netherton Syndrome

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Sources:
47OMIM, 10Disease Ontology, 11diseasecard, 43NIH Rare Diseases, 23Genetics Home Reference, 12DISEASES, 45Novoseek, 49Orphanet, 62UMLS, 22GeneTests, 24GTR, 35MeSH, 28ICD10 via Orphanet
See all sources

Netherton Syndrome, Aliases & Descriptions:

Name: Netherton Syndrome 47 10 11 43 23 12 45 49
Netherton Disease 43 22 23 24
Bamboo Hair Syndrome 43 23 49
Ns 43 23 49
Ichthyosis Linearis Circumflexa 23 62
Comèl-Netherton Syndrome 43 49
 
Comel-Netherton Syndrome 23 62
Neth 43 23
Ichthyosiform Erythroderma with Hypotrichosis and Hyper-Ige 23
N Syndrome 62
Ilc 23


Classifications:

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


Characteristics (Orphanet epidemiological data):

49
netherton syndrome:
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy


External Ids:

OMIM47 256500
Disease Ontology10 DOID:0050474
MeSH35 D056770
Orphanet49 634
ICD10 via Orphanet28 Q80.3

Related Diseases for Netherton Syndrome

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



Diseases related to netherton syndrome

Symptoms for Netherton Syndrome

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Symptoms by clinical synopsis from OMIM:

256500

Clinical features from OMIM:

256500

Symptoms:

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

HPO human phenotypes related to Netherton Syndrome:

(show all 37)
id Description Frequency HPO Source Accession
1 acanthosis nigricans hallmark (90%) HP:0000956
2 eczema hallmark (90%) HP:0000964
3 urticaria hallmark (90%) HP:0001025
4 malabsorption hallmark (90%) HP:0002024
5 asthma hallmark (90%) HP:0002099
6 fine hair hallmark (90%) HP:0002213
7 irregular hyperpigmentation hallmark (90%) HP:0007400
8 ichthyosis hallmark (90%) HP:0008064
9 abnormal hair quantity hallmark (90%) HP:0011362
10 cognitive impairment hallmark (90%) HP:0100543
11 seizures typical (50%) HP:0001250
12 emphysema typical (50%) HP:0002097
13 recurrent respiratory infections typical (50%) HP:0002205
14 hypogammaglobulinemia typical (50%) HP:0004313
15 dry skin occasional (7.5%) HP:0000958
16 skin rash occasional (7.5%) HP:0000988
17 dehydration occasional (7.5%) HP:0001944
18 aminoaciduria occasional (7.5%) HP:0003355
19 short stature occasional (7.5%) HP:0004322
20 abnormal localization of kidney occasional (7.5%) HP:0100542
21 aplasia/hypoplasia of the eyebrow occasional (7.5%) HP:0100840
22 autosomal recessive inheritance HP:0000007
23 sparse eyebrow HP:0000535
24 erythroderma HP:0001019
25 urticaria HP:0001025
26 global developmental delay HP:0001263
27 failure to thrive HP:0001508
28 asthma HP:0002099
29 sparse scalp hair HP:0002209
30 brittle hair HP:0002299
31 recurrent infections HP:0002719
32 abnormality of the musculature HP:0003011
33 increased ige level HP:0003212
34 hypernatremic dehydration HP:0004906
35 congenital nonbullous ichthyosiform erythroderma HP:0007479
36 villous atrophy HP:0011473
37 angioedema HP:0100665

Drugs & Therapeutics for Netherton Syndrome

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Drug clinical trials:

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Search NIH Clinical Center for Netherton Syndrome

Genetic Tests for Netherton Syndrome

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Genetic tests related to Netherton Syndrome:

id Genetic test Affiliating Genes
1 Netherton Syndrome22 24 SPINK5

Anatomical Context for Netherton Syndrome

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MalaCards organs/tissues related to Netherton Syndrome:

33
Skin, Kidney, Eye, B cells, Testes, Thymus

Animal Models for Netherton Syndrome or affiliated genes

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Publications for Netherton Syndrome

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Articles related to Netherton Syndrome:

(show top 50)    (show all 120)
idTitleAuthorsYear
1
Recurrent pustular eruption masquerading as pustular psoriasis in Netherton syndrome. (25440527)
2015
2
Netherton syndrome associated with growth hormone deficiency. (24015757)
2014
3
Molecular analysis of a series of Israeli families with ComA"l-Netherton syndrome. (24577329)
2014
4
Netherton syndrome with ichthyosis linearis circumflexa and trichorrhexis invaginatum. (25526335)
2014
5
Phase I study protocol for ex-vivo lentiviral gene therapy for the inherited skin disease, Netherton Syndrome. (24138501)
2013
6
Netherton syndrome: skin inflammation and allergy by loss of protease inhibition. (23344365)
2013
7
Complete Maternal Isodisomy of Chromosome 5 in a Japanese Patient with Netherton Syndrome. (24042343)
2013
8
Case of Netherton syndrome with an elevated serum thymus and activation-regulated chemokine level. (23802543)
2013
9
Netherton syndrome - Why ENT surgeons should be aware of this rare disease - report of a case. (23829563)
2013
10
Netherton syndrome with multiple non-melanoma skin cancers. (23571873)
2013
11
Aberrant distribution patterns of corneodesmosomal components of tape-stripped corneocytes in atopic dermatitis and related skin conditions (ichthyosis vulgaris, Netherton syndrome and peeling skin syndrome type B). (23810772)
2013
12
Netherton syndrome, a case report and review of literature. (24800031)
2013
13
The identification of a new role for LEKTI in the skin: The use of protein 'bait' arrays to detect defective trafficking of dermcidin in the skin of patients with Netherton syndrome. (22588119)
2012
14
Narrowband ultraviolet B phototherapy associated with improvement in Netherton syndrome. (22582910)
2012
15
Clinical expression and new SPINK5 splicing defects in Netherton syndrome: unmasking a frequent founder synonymous mutation and unconventional intronic mutations. (22089833)
2012
16
Netherton syndrome showing a large clinical overlap with generalized inflammatory peeling skin syndrome. (22562784)
2012
17
Prenatal diagnosis of Comel-Netherton syndrome with PGD, case report and review article. (21573681)
2011
18
Infliximab infusions for Netherton syndrome: sustained clinical improvement correlates with a reduction of thymic stromal lymphopoietin levels in the skin. (21654837)
2011
19
Picture of the month. ComA"l-Netherton syndrome without bamboo hair. (21810639)
2011
20
Videodermoscopy of eyelashes in Netherton syndrome. (21108664)
2011
21
Netherton syndrome: A rare genodermatosis. (23130216)
2011
22
Par2 inactivation inhibits early production of TSLP, but not cutaneous inflammation, in Netherton syndrome adult mouse model. (20703245)
2010
23
The safety and efficacy of pimecrolimus, 1%, cream for the treatment of Netherton syndrome: results from an exploratory study. (20083693)
2010
24
Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing. (20179351)
2010
25
Netherton syndrome: dental considerations. (19953815)
2009
26
Netherton syndrome: mutation analysis of two Taiwanese families. (17415575)
2007
27
Early skeletal signs in Netherton syndrome. (17156006)
2006
28
Netherton syndrome]. (16956571)
2006
29
Netherton syndrome: a case report and review of the literature. (16796630)
2006
30
SPINK5, the defective gene in netherton syndrome, encodes multiple LEKTI isoforms derived from alternative pre-mRNA processing. (16374478)
2006
31
A case of a Japanese neonate with congenital ichthyosiform erythroderma diagnosed as Netherton syndrome. (16901309)
2006
32
Characterization and expression analysis of the Spink5 gene, the mouse ortholog of the defective gene in Netherton syndrome. (15780751)
2005
33
Comel-Netherton syndrome in brothers and expression of cytokeratins. (15793546)
2005
34
Acute pancreatitis in a young girl with the Netherton syndrome. (16291148)
2005
35
Netherton syndrome: a type of infantile erythroderma with failure to thrive, immune deficiency, rickets. Report of 3 cases]. (15935629)
2005
36
Lethal, neonatal ichthyosis with increased proteolytic processing of filaggrin in a mouse model of Netherton syndrome. (15590704)
2005
37
UVA1 phototherapy of Netherton syndrome. (15040483)
2004
38
Netherton syndrome. (14673256)
2003
39
Elevated stratum corneum hydrolytic activity in Netherton syndrome suggests an inhibitory regulation of desquamation by SPINK5-derived peptides. (11874482)
2002
40
Netherton syndrome associated with idiopathic congenital hemihypertrophy. (12220283)
2002
41
Prenatal diagnosis of a lethal form of Netherton syndrome by SPINK5 mutation analysis. (11857617)
2002
42
Genetic analysis of a severe case of Netherton syndrome and application for prenatal testing. (11952552)
2002
43
Severe hypernatremic dehydration in an infant with Netherton syndrome. (11693786)
2001
44
Increasing the likelihood of early diagnosis of Netherton syndrome by simple examination of eyebrow hairs. (10724214)
2000
45
Comel-Netherton syndrome: evolution of manifestation in a 20-year follow-up and phenotypic overlap with peeling skin syndrome type B. (10954215)
2000
46
Altered lamellar body secretion and stratum corneum membrane structure in Netherton syndrome: differentiation from other infantile erythrodermas and pathogenic implications. (10411158)
1999
47
Comel-Netherton syndrome. A diagnostic challenge. (9349353)
1997
48
ComA"l-Netherton syndrome. (7999614)
1994
49
Netherton syndrome revisited. (8170853)
1994
50
Netherton syndrome, enteropathic acrodermatitis, and zinc. (70613)
1977

Variations for Netherton Syndrome

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Clinvar genetic disease variations for Netherton Syndrome:

7
id Gene Variation Type Significance SNP ID Assembly Location
1SPINK5NM_006846.3(SPINK5): c.2368C> T (p.Arg790Ter)single nucleotide variantPathogenicrs121908387GRCh37Chr 5, 147499626: 147499626
2SPINK5SPINK5, IVS4AS, A-T, -2single nucleotide variantPathogenic
3SPINK5SPINK5, 1-BP INS, 2468AinsertionPathogenic

Expression for genes affiliated with Netherton Syndrome

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Search GEO for disease gene expression data for Netherton Syndrome.

Pathways for genes affiliated with Netherton Syndrome

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Pathways related to Netherton Syndrome according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.3KLK7, ELANE

Compounds for genes affiliated with Netherton Syndrome

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Sources:
45Novoseek, 13DrugBank, 26HMDB
See all sources

Compounds related to Netherton Syndrome according to GeneCards/GeneDecks:

(show all 16)
idCompoundScoreTop Affiliating Genes
1tlck459.7CTRL, ELANE
23,4-dichloroisocoumarin45 1310.7ELANE, CTRL
3tannins459.7CTRL, ELANE
4chymostatin459.7CTRL, ELANE
5pmsf459.7CTRL, ELANE
6aebsf459.6ELANE, CTRL
7diisopropylfluorophosphate459.6CTRL, ELANE
8phosphoramidon45 1310.6CTRL, ELANE
9leupeptin459.5ELANE, CTRL
10egcg459.4CTRL, ELANE
11fmlp459.3CTRL, ELANE
12vitamin d459.1ELANE, TGM1
13sodium dodecylsulfate458.9CTRL, ELANE, TGM1
14vitamin a45 26 1310.8ELANE, TGM1
15serine458.5SPINK5, ELANE, KLK7, CTRL
16retinoic acid45 269.2TGM1, ELANE, KLK7, CTRL

GO Terms for genes affiliated with Netherton Syndrome

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Cellular components related to Netherton Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1epidermal lamellar bodyGO:00972099.1KLK7, SPINK5
2extracellular regionGO:00055768.9KLK7, ELANE, SPINK5

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

idNameGO IDScoreTop Affiliating Genes
1proteolysisGO:00065089.4CTRL, ELANE
2extracellular matrix disassemblyGO:00226179.0KLK7, ELANE
3extracellular matrix organizationGO:00301988.8KLK7, ELANE, SPINK5

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

idNameGO IDScoreTop Affiliating Genes
1serine-type endopeptidase activityGO:00042528.8CTRL, KLK7, ELANE

Products for genes affiliated with Netherton Syndrome

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Sources for Netherton Syndrome

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4CDC
15ExPASy
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
52PubMed
53QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet