MCID: NTH001
MIFTS: 51

Netherton Syndrome malady

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

Aliases & Classifications for Netherton Syndrome

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Aliases & Descriptions for Netherton Syndrome:

Name: Netherton Syndrome 49 10 11 45 23 47 12 51 36 67
Netherton Disease 45 22 23 24 67
Neth 45 22 23 67
Ichthyosis Linearis Circumflexa 22 23 65
Ns 23 51 67
Comel-Netherton Syndrome 23 67
Bamboo Hair Syndrome 23 51
 
Erythroderma, Ichthyosiform, with Hypotrichosis and Hyper-Ige 67
Ichthyosiform Erythroderma with Hypotrichosis and Hyper-Ige 23
Comèl-Netherton Syndrome 51
N Syndrome 22
Ilc 23
Nts 67


Classifications:



Characteristics (Orphanet epidemiological data):

51
netherton syndrome:
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy


External Ids:

OMIM49 256500
Disease Ontology10 DOID:0050474
MeSH36 D056770
Orphanet51 634
ICD10 via Orphanet28 Q80.8
MedGen34 C0265962

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 ischemia and ichthyosis vulgaris, and has symptoms including acanthosis nigricans, eczema and urticaria. An important gene associated with Netherton Syndrome is SPINK5 (Serine Peptidase Inhibitor, Kazal Type 5). Affiliated tissues include skin, kidney and b cells.

NIH Rare Diseases:45 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

UniProtKB/Swiss-Prot:67 Netherton syndrome: An autosomal recessive congenital ichthyosis associated with hair shaft abnormalities and anomalies of the immune system. Typical features are ichthyosis linearis circumflexa, ichthyosiform erythroderma, trichorrhexis invaginata (bamboo hair), atopic dermatitis, and hayfever. High postnatal mortality is due to failure to thrive, infections and hypernatremic dehydration.

Wikipedia:68 Netherton syndrome is a severe, autosomal recessive form of ichthyosis associated with mutations in the... more...

Description from OMIM:49 256500

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:

 51 (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 36)
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 abnormal hair quantity hallmark (90%) HP:0011362
9 cognitive impairment hallmark (90%) HP:0100543
10 seizures typical (50%) HP:0001250
11 emphysema typical (50%) HP:0002097
12 recurrent respiratory infections typical (50%) HP:0002205
13 decreased antibody level in blood typical (50%) HP:0004313
14 dry skin occasional (7.5%) HP:0000958
15 skin rash occasional (7.5%) HP:0000988
16 dehydration occasional (7.5%) HP:0001944
17 aminoaciduria occasional (7.5%) HP:0003355
18 short stature occasional (7.5%) HP:0004322
19 abnormal localization of kidney occasional (7.5%) HP:0100542
20 aplasia/hypoplasia of the eyebrow occasional (7.5%) HP:0100840
21 autosomal recessive inheritance HP:0000007
22 sparse eyebrow HP:0000535
23 erythroderma HP:0001019
24 urticaria HP:0001025
25 global developmental delay HP:0001263
26 failure to thrive HP:0001508
27 asthma HP:0002099
28 sparse scalp hair HP:0002209
29 brittle hair HP:0002299
30 recurrent infections HP:0002719
31 abnormality of the musculature HP:0003011
32 increased ige level HP:0003212
33 hypernatremic dehydration HP:0004906
34 congenital nonbullous ichthyosiform erythroderma HP:0007479
35 villous atrophy HP:0011473
36 angioedema HP:0100665

Drugs & Therapeutics for Netherton Syndrome

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

idNameStatusPhaseClinical TrialsCas NumberPubChem Id
1
Pimecrolimusapproved, investigationalPhase 1, Phase 260137071-32-06447131, 17753757
Synonyms:
(3S,4R,5S,8R,9E,12S,14S,15R,16S,18R,19R,26aS)-3-((E)-2-((1R,3R,4S)-4-chloro-3-methoxycyclohexyl)-1-methylvinyl)-8-ethyl-5,6,8,11,12,13,14,15,16,17,18,19,24,26,26a-hexadecahydro-5,19-epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclotricosine-1,17,20,21(4H,23H)-tetrone
137071-32-0
33-Epi-chloro-33-desoxyascomycin
33-epi-Chloro-33-desoxyascomycin
ASM 981
ASM-981
ASM-998
CHEMBL1200686
CID6447131
CID6509979
CID6916008
D05480
DB00337
 
Elidel
Elidel (TN)
I06-1252
LS-181798
MolPort-003-666-749
NCGC00167506-01
Pimecrolimus
Pimecrolimus (JAN/USAN/INN)
Pimecrolimus [USAN:INN:BAN]
Pimecrolimusum
S5004_Selleck
SDZ ASM 981
SDZ-ASM 981
SDZ-ASM-981
UNII-7KYV510875
2
Tacrolimusapproved, investigationalPhase 1, Phase 2992104987-11-3445643, 439492, 445647, 439492, 445647
Synonyms:
(-)-FK 506
(3S,4R,5S,8R,9E,12S,14S,15R,16S,18R,19R,26aS)-5,19-dihydroxy-3-{(1E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl}-14,16-dimethoxy-4,10,12,18-tetramethyl-8-(prop-2-en-1-yl)-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-3H-15,19-epoxypyrido[2,1-c][1,4]oxazacyclotricosine-1,7,20,21(4H,23H)-tetrone
104987-11-3
109581-93-3 (Hydrate)
15,19-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclotricosine-1,7,20,21(23H)-tetrone,
3S-[3R*[E(1S*,3S*,4S*)],4S*,5R*,8S*,9E,12R*,14R*,15S*,16R*,18S*,19S*,26aR*]]-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5, 19-dihydroxy-3-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl]-14,16-dimethoxy-4,10,12,18-tetramethyl-8-(2-propenyl)-15,19-epoxy-3H-pyrido[2,1-c] [1,4] oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone
8-DEETHYL-8-[BUT-3-ENYL]-ASCOMYCIN
8-DEETHYL-8-[but-3-enyl]-ascomycin
AC-1182
AC1L1K7H
AC1L97GB
AC1L9IBU
AKOS005145901
Advagraf
Ambap104987-11-3
Ambap5429
BCBcMAP01_000194
BRD-K35452788-001-02-1
BSPBio-001279
BSPBio_001279
Bio-0921
Bio2_000470
Bio2_000950
C01375
C44H69NO10
CCRIS 7124
CHEBI:100924
CHEBI:61049
CHEMBL1200738
CID11158639
CID11556866
CID439492
CID445643
CID5372
CID5472317
CID6426916
CID6436007
CID6473866
CID6536850
CID6610362
CID6912836
CID9832283
CID9853905
CID9918805
CID9940643
CID9963169
CPD-10016
CPD000466356
D08556
DB00864
DivK1c_001040
FK 506
FK-506
FK5
FK506
FR 900506
FR-900506
FR900506
 
FT-0082660
Fk-506
Fujimycin
Graceptor
HMS1362O21
HMS1792O21
HMS1990O21
HMS2051C18
HMS2093M19
HMS503O21
Hecoria
IDI1_001040
IDI1_002225
K506
KBio1_001040
KBio2_000619
KBio2_003187
KBio2_005755
KBio3_001097
KBio3_001098
KBioGR_000619
KBioSS_000619
L 679934
L-679934
LCP-Tacro
LMPK04000003
LS-64247
MLS000759471
MLS001424054
Modigraf
MolPort-003-666-518
NCGC00163470-01
NCGC00163470-02
NCGC00163470-03
NCGC00163470-04
NCGC00179232-01
NChemBio.2007.16-comp1
NINDS_001040
NSC717865
Prograf
Prograf (TN)
Protopic
Protopy
S5003_Selleck
SAM001246677
SMR000466356
Tacarolimus
Tacrolimus
Tacrolimus (INN)
Tacrolimus (Prograf?)
Tacrolimus (anhydrous)
Tacrolimus Hydrate
Tacrolimus anhydrous
Tacrolimus hydrate
Tsukubaenolide
UNII-Y5L2157C4J
nchembio.2007.23-comp2
tacrolimus
tacrolimus hydrate
3
AdalimumabapprovedPhase 2411331731-18-116219006
Synonyms:
331731-18-1
Adalimumab
Adalimumab (USAN/INN)
Adalimumab (genetical recombination)
 
Adalimumab (genetical recombination) (JAN)
D02597
Humira
Humira (TN)
Humira Pen
Ig gamma-1 chain C region

Interventional clinical trials:

idNameStatusNCT IDPhase
1Safety Study of Elidel (Pimecrolimus) 1% Cream to Treat Netherton SyndromeCompletedNCT00208026Phase 1, Phase 2
2Clinical Trial Using Humira in Netherton SyndromeRecruitingNCT02113904Phase 2
3A Study Evaluating the Safety and Efficacy of Topical BPR277 for the Treatment of Atopic Dermatitis and Netherton SyndromeCompletedNCT01428297Phase 1
4Gene Therapy for Netherton SyndromeRecruitingNCT01545323Phase 1
5Natural History and Biological Study of Netherton SyndromeRecruitingNCT02081313
6Natural History of Diseases Associated With Allergic Inflammation: Atopic Dermatitis and Genetic and Congenital Diseases Associated With Atopic PathwaysRecruitingNCT01164241

Search NIH Clinical Center for Netherton Syndrome


Cochrane evidence based reviews: 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, B cells, Eye, 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 126)
idTitleAuthorsYear
1
Severe lethal phenotype of a Japanese case of Netherton syndrome with homozygous founder mutations of SPINK5 c.375_376delAT. (26365906)
2015
2
Betapapillomavirus in multiple non-melanoma skin cancers of Netherton syndrome: Case report and published work review. (25917539)
2015
3
Recurrent pustular eruption masquerading as pustular psoriasis in Netherton syndrome. (25440527)
2015
4
Netherton syndrome associated with growth hormone deficiency. (24015757)
2014
5
Molecular analysis of a series of Israeli families with ComA"l-Netherton syndrome. (24577329)
2014
6
Netherton syndrome with ichthyosis linearis circumflexa and trichorrhexis invaginatum. (25526335)
2014
7
Phase I study protocol for ex-vivo lentiviral gene therapy for the inherited skin disease, Netherton Syndrome. (24138501)
2013
8
Netherton syndrome: skin inflammation and allergy by loss of protease inhibition. (23344365)
2013
9
Complete Maternal Isodisomy of Chromosome 5 in a Japanese Patient with Netherton Syndrome. (24042343)
2013
10
Case of Netherton syndrome with an elevated serum thymus and activation-regulated chemokine level. (23802543)
2013
11
Netherton syndrome - Why ENT surgeons should be aware of this rare disease - report of a case. (23829563)
2013
12
Netherton syndrome with multiple non-melanoma skin cancers. (23571873)
2013
13
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
14
Netherton syndrome, a case report and review of literature. (24800031)
2013
15
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
16
Narrowband ultraviolet B phototherapy associated with improvement in Netherton syndrome. (22582910)
2012
17
Clinical expression and new SPINK5 splicing defects in Netherton syndrome: unmasking a frequent founder synonymous mutation and unconventional intronic mutations. (22089833)
2012
18
Netherton syndrome showing a large clinical overlap with generalized inflammatory peeling skin syndrome. (22562784)
2012
19
Prenatal diagnosis of Comel-Netherton syndrome with PGD, case report and review article. (21573681)
2011
20
Infliximab infusions for Netherton syndrome: sustained clinical improvement correlates with a reduction of thymic stromal lymphopoietin levels in the skin. (21654837)
2011
21
Picture of the month. ComA"l-Netherton syndrome without bamboo hair. (21810639)
2011
22
Videodermoscopy of eyelashes in Netherton syndrome. (21108664)
2011
23
Par2 inactivation inhibits early production of TSLP, but not cutaneous inflammation, in Netherton syndrome adult mouse model. (20703245)
2010
24
The safety and efficacy of pimecrolimus, 1%, cream for the treatment of Netherton syndrome: results from an exploratory study. (20083693)
2010
25
Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing. (20179351)
2010
26
Netherton syndrome: dental considerations. (19953815)
2009
27
Netherton syndrome: mutation analysis of two Taiwanese families. (17415575)
2007
28
Early skeletal signs in Netherton syndrome. (17156006)
2006
29
Netherton syndrome]. (16956571)
2006
30
Netherton syndrome: a case report and review of the literature. (16796630)
2006
31
SPINK5, the defective gene in netherton syndrome, encodes multiple LEKTI isoforms derived from alternative pre-mRNA processing. (16374478)
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:

5
id Gene Variation Type Significance SNP ID Assembly Location
1SPINK5NM_006846.3(SPINK5): c.2368C> T (p.Arg790Ter)single nucleotide variantPathogenicrs121908387GRCh37Chr 5, 147499626: 147499626
2SPINK5NM_006846.3(SPINK5): c.283-2A> Tsingle nucleotide variantPathogenicrs587777749GRCh38Chr 5, 148086403: 148086403
3SPINK5NM_006846.3(SPINK5): c.2468dupA (p.Lys824Glufs)duplicationPathogenicrs587777750GRCh38Chr 5, 148120321: 148120321

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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GO Terms for genes affiliated with Netherton Syndrome

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Cellular components related to Netherton Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1epidermal lamellar bodyGO:009720910.4KLK7, SPINK5
2extracellular exosomeGO:00700627.4DSG1, ELANE, PI3, SLC26A2, SPINK5, TGM1

Biological processes related to Netherton Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1keratinocyte differentiationGO:00302169.6FLG, TGM1
2extracellular matrix organizationGO:00301989.4ELANE, KLK7, SPINK5

Molecular functions related to Netherton Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1peptidase inhibitor activityGO:00304149.7PI3, SPINK5
2serine-type endopeptidase inhibitor activityGO:00048679.3PI3, SPINK5
3serine-type endopeptidase activityGO:00042529.3CTRL, ELANE, KLK7
4peptidase activityGO:00082339.0CTRL, ELANE, KLK7

Sources for Netherton Syndrome

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2CDC
14ExPASy
15FDA
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
34MedGen
36MeSH
37MESH via Orphanet
38MGI
41NCI
42NCIt
43NDF-RT
46NINDS
47Novoseek
49OMIM
50OMIM via Orphanet
54PubMed
55QIAGEN
60SNOMED-CT via Orphanet
64Tumor Gene Family of Databases
65UMLS
66UMLS via Orphanet