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Netherton syndrome(NETH)

MedGen UID:
1802991
Concept ID:
C5574950
Disease or Syndrome
Synonyms: COMEL-NETHERTON SYNDROME; ERYTHRODERMA, ICHTHYOSIFORM, WITH HYPOTRICHOSIS AND HYPER-IgE; NETH; Netherton disease
SNOMED CT: Netherton's syndrome (312514006); Comel-Netherton syndrome (312514006); Axial osteosclerosis with bamboo hair (312514006); Netherton syndrome (312514006); Netherton's disease (34638006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SPINK5 (5q32)
 
Monarch Initiative: MONDO:0009735
OMIM®: 256500
Orphanet: ORPHA634

Definition

Netherton syndrome (NETH) is a rare and severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. Generalized scaly erythroderma is apparent at or soon after birth and usually persists. Scalp hair is sparse and brittle with a characteristic 'bamboo' shape under light microscopic examination due to invagination of the distal part of the hair shaft to its proximal part. Atopic manifestations include eczema-like rashes, atopic dermatitis, pruritus, hay fever, angioedema, urticaria, high levels of IgE in the serum, and hypereosinophilia. Life-threatening complications are frequent during the neonatal period, including hypernatremic dehydration, hypothermia, extreme weight loss, bronchopneumonia, and sepsis. During childhood, failure to thrive is common as a result of malnutrition, metabolic disorders, chronic erythroderma, persistent cutaneous infections, or enteropathy (summary by Bitoun et al., 2002). [from OMIM]

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Intestinal atresia
MedGen UID:
7129
Concept ID:
C0021828
Disease or Syndrome
An abnormal closure, or atresia of the tubular structure of the intestine.
Villous atrophy
MedGen UID:
154306
Concept ID:
C0554101
Finding
The enteric villi are atrophic or absent.
Recurrent infection of the gastrointestinal tract
MedGen UID:
343135
Concept ID:
C1854495
Disease or Syndrome
Recurrent infection of the gastrointestinal tract.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Asthma
MedGen UID:
2109
Concept ID:
C0004096
Disease or Syndrome
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Erythroderma
MedGen UID:
3767
Concept ID:
C0011606
Disease or Syndrome
An inflammatory exfoliative dermatosis involving nearly all of the surface of the skin. Erythroderma develops suddenly. A patchy erythema may generalize and spread to affect most of the skin. Scaling may appear in 2-6 days and be accompanied by hot, red, dry skin, malaise, and fever.
Eczematoid dermatitis
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
Sepsis
MedGen UID:
48626
Concept ID:
C0036690
Disease or Syndrome
Systemic inflammatory response to infection.
Increased circulating IgE concentration
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
Hypereosinophilia
MedGen UID:
148170
Concept ID:
C0745091
Disease or Syndrome
A severely increased count of eosinophils in the blood defined as a blood eosinophil count of at least 1.5 billion cells per liter.
Recurrent skin infections
MedGen UID:
377848
Concept ID:
C1853193
Disease or Syndrome
Infections of the skin that happen multiple times.
Allergic rhinitis
MedGen UID:
382012
Concept ID:
C2607914
Disease or Syndrome
It is characterized by one or more symptoms including sneezing, itching, nasal congestion, and rhinorrhea.
Food allergy
MedGen UID:
1635115
Concept ID:
C4554344
Disease or Syndrome
Primary food allergies primarily occur as a result (most likely) of gastrointestinal sensitization to predominantly stable food allergens (glycoproteins). A secondary food allergy develops after primary sensitization to airborne allergens (e. g., pollen allergens) with subsequent reactions (due to cross-reactivity) to structurally related often labile allergens in (plant) foods.
Decreased circulating IgG concentration
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Hypernatremic dehydration
MedGen UID:
340564
Concept ID:
C1850544
Finding
Dehydration resulting from abnormally high levels of sodium in the blood. Infants and individuals that are intubated are at highest risk.
Chronic rhinitis
MedGen UID:
3086
Concept ID:
C0008711
Disease or Syndrome
Chronic inflammation of the nasal mucosa.
Sparse eyebrow
MedGen UID:
371332
Concept ID:
C1832446
Finding
Decreased density/number of eyebrow hairs.
Sparse scalp hair
MedGen UID:
346499
Concept ID:
C1857042
Finding
Decreased number of hairs per unit area of skin of the scalp.
Angioedema
MedGen UID:
1543
Concept ID:
C0002994
Pathologic Function
Rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa and submucosal tissues of the skin of the face, normally around the mouth, and the mucosa of the mouth and/or throat, as well as the tongue during a period of minutes to several hours. The swelling can also occur elsewhere, typically in the hands. Angioedema is similar to urticaria, but the swelling is subcutaneous rather than on the epidermis.
Parakeratosis
MedGen UID:
10572
Concept ID:
C0030436
Disease or Syndrome
Abnormal formation of the keratinocytes of the epidermis characterized by persistence of nuclei, incomplete formation of keratin, and moistness and swelling of the keratinocytes.
Urticaria
MedGen UID:
22587
Concept ID:
C0042109
Disease or Syndrome
Raised, well-circumscribed areas of erythema and edema involving the dermis and epidermis. Urticaria is intensely pruritic, and blanches completely with pressure.
Congenital nonbullous ichthyosiform erythroderma
MedGen UID:
38180
Concept ID:
C0079154
Disease or Syndrome
The term collodion baby applies to newborns who appear to have an extra layer of skin (known as a collodion membrane) that has a collodion-like quality. It is a descriptive term, not a specific diagnosis or disorder (as such, it is a syndrome). Affected babies are born in a collodion membrane, a shiny waxy outer layer to the skin. This is shed 10-14 days after birth, revealing the main symptom of the disease, extensive scaling of the skin caused by hyperkeratosis. With increasing age, the scaling tends to be concentrated around joints in areas such as the groin, the armpits, the inside of the elbow and the neck. The scales often tile the skin and may resemble fish scales.
Brittle hair
MedGen UID:
120480
Concept ID:
C0263490
Disease or Syndrome
Fragile, easily breakable hair, i.e., with reduced tensile strength.
Brittle scalp hair
MedGen UID:
870836
Concept ID:
C4025296
Finding
Fragile, easily breakable scalp hair.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVNetherton syndrome

Professional guidelines

PubMed

Odorici G, Schenetti C, Marzola E, Monti A, Borghi A, Corazza M
J Dtsch Dermatol Ges 2022 Dec;20(12):1636-1640. Epub 2022 Nov 2 doi: 10.1111/ddg.14914. PMID: 36321361
Joosten MDW, Clabbers JMK, Jonca N, Mazereeuw-Hautier J, Gostyński AH
Orphanet J Rare Dis 2022 Jul 15;17(1):269. doi: 10.1186/s13023-022-02430-6. PMID: 35840979Free PMC Article
Sarri CA, Roussaki-Schulze A, Vasilopoulos Y, Zafiriou E, Patsatsi A, Stamatis C, Gidarokosta P, Sotiriadis D, Sarafidou T, Mamuris Z
Mol Diagn Ther 2017 Apr;21(2):137-152. doi: 10.1007/s40291-016-0243-y. PMID: 27905021

Recent clinical studies

Etiology

Morita A, Okubo Y, Imafuku S, Terui T
J Dermatol 2024 Nov;51(11):1379-1391. Epub 2024 Oct 7 doi: 10.1111/1346-8138.17449. PMID: 39373152
Lefferdink R, Rangel SM, Chima M, Ibler E, Pavel AB, Kim H, Wu B, Abu-Zayed H, Wu J, Jackson K, Singer G, Choate KA, Guttman-Yassky E, Paller AS
Arch Dermatol Res 2023 Mar;315(2):305-315. Epub 2022 Feb 26 doi: 10.1007/s00403-022-02325-3. PMID: 35218370Free PMC Article
Cuperus E, Bygum A, Boeckmann L, Bodemer C, Bolling MC, Caproni M, Diociaiuti A, Emmert S, Fischer J, Gostynski A, Guez S, van Gijn ME, Hannulla-Jouppi K, Has C, Hernández-Martín A, Martinez AE, Mazereeuw-Hautier J, Medvecz M, Neri I, Sigurdsson V, Suessmuth K, Traupe H, Oji V, Pasmans SGMA
J Eur Acad Dermatol Venereol 2022 Jul;36(7):973-986. Epub 2022 Mar 15 doi: 10.1111/jdv.18043. PMID: 35238435Free PMC Article
Al-Shaikhly T, Ochs HD
Immunol Cell Biol 2019 Apr;97(4):368-379. Epub 2018 Nov 19 doi: 10.1111/imcb.12209. PMID: 30264496
Fraitag S, Bodemer C
Curr Opin Pediatr 2010 Aug;22(4):438-44. doi: 10.1097/MOP.0b013e32833bc396. PMID: 20616730

Diagnosis

Drivenes JL, Bygum A
JAMA Dermatol 2022 Nov 1;158(11):1315. doi: 10.1001/jamadermatol.2022.3796. PMID: 36169939
Al-Shaikhly T, Ochs HD
Immunol Cell Biol 2019 Apr;97(4):368-379. Epub 2018 Nov 19 doi: 10.1111/imcb.12209. PMID: 30264496
Sarri CA, Roussaki-Schulze A, Vasilopoulos Y, Zafiriou E, Patsatsi A, Stamatis C, Gidarokosta P, Sotiriadis D, Sarafidou T, Mamuris Z
Mol Diagn Ther 2017 Apr;21(2):137-152. doi: 10.1007/s40291-016-0243-y. PMID: 27905021
Yoneda K
J Dermatol 2016 Mar;43(3):252-63. doi: 10.1111/1346-8138.13284. PMID: 26945533
Fraitag S, Bodemer C
Curr Opin Pediatr 2010 Aug;22(4):438-44. doi: 10.1097/MOP.0b013e32833bc396. PMID: 20616730

Therapy

Olbrich H, Sadik CD, Ludwig RJ, Thaçi D, Boch K
Biomolecules 2023 Mar 31;13(4) doi: 10.3390/biom13040634. PMID: 37189381Free PMC Article
Samuelov L, Shehadeh W, Sarig O, Gat A, Matz H, Sprecher E
J Dermatol 2023 Apr;50(4):494-499. Epub 2022 Nov 23 doi: 10.1111/1346-8138.16645. PMID: 36419401
Lefferdink R, Rangel SM, Chima M, Ibler E, Pavel AB, Kim H, Wu B, Abu-Zayed H, Wu J, Jackson K, Singer G, Choate KA, Guttman-Yassky E, Paller AS
Arch Dermatol Res 2023 Mar;315(2):305-315. Epub 2022 Feb 26 doi: 10.1007/s00403-022-02325-3. PMID: 35218370Free PMC Article
Muñoz-Bellido FJ, Moreno E, Dávila I
J Investig Allergol Clin Immunol 2022 Apr 19;32(2):97-115. Epub 2021 Mar 3 doi: 10.18176/jiaci.0682. PMID: 33661102
Chia JC, Mydlarski PR
J Dermatolog Treat 2017 Jun;28(4):332-337. Epub 2016 Nov 7 doi: 10.1080/09546634.2016.1249819. PMID: 27759482

Prognosis

Cuperus E, Bygum A, Boeckmann L, Bodemer C, Bolling MC, Caproni M, Diociaiuti A, Emmert S, Fischer J, Gostynski A, Guez S, van Gijn ME, Hannulla-Jouppi K, Has C, Hernández-Martín A, Martinez AE, Mazereeuw-Hautier J, Medvecz M, Neri I, Sigurdsson V, Suessmuth K, Traupe H, Oji V, Pasmans SGMA
J Eur Acad Dermatol Venereol 2022 Jul;36(7):973-986. Epub 2022 Mar 15 doi: 10.1111/jdv.18043. PMID: 35238435Free PMC Article
Samuelov L, Sprecher E
J Allergy Clin Immunol 2014 Oct;134(4):808-15. doi: 10.1016/j.jaci.2014.07.061. PMID: 25282561
D'Alessio M, Fortugno P, Zambruno G, Hovnanian A
G Ital Dermatol Venereol 2013 Feb;148(1):37-51. PMID: 23407075
Fraitag S, Bodemer C
Curr Opin Pediatr 2010 Aug;22(4):438-44. doi: 10.1097/MOP.0b013e32833bc396. PMID: 20616730
Galadari I, Al-Kaabi J, Galadari H
Skinmed 2003 Nov-Dec;2(6):387-9. doi: 10.1111/j.1540-9740.2003.02430.x. PMID: 14673256

Clinical prediction guides

Martin-García C, Godoy E, Cabrera A, Cañueto J, Muñoz-Bellido FJ, Perez-Pazos J, Dávila I
Int J Immunopathol Pharmacol 2023 Jan-Dec;37:3946320231172881. doi: 10.1177/03946320231172881. PMID: 37200480Free PMC Article
Samuelov L, Shehadeh W, Sarig O, Gat A, Matz H, Sprecher E
J Dermatol 2023 Apr;50(4):494-499. Epub 2022 Nov 23 doi: 10.1111/1346-8138.16645. PMID: 36419401
Lefferdink R, Rangel SM, Chima M, Ibler E, Pavel AB, Kim H, Wu B, Abu-Zayed H, Wu J, Jackson K, Singer G, Choate KA, Guttman-Yassky E, Paller AS
Arch Dermatol Res 2023 Mar;315(2):305-315. Epub 2022 Feb 26 doi: 10.1007/s00403-022-02325-3. PMID: 35218370Free PMC Article
Rudnicka L, Olszewska M, Waśkiel A, Rakowska A
Dermatol Clin 2018 Oct;36(4):421-430. Epub 2018 Aug 16 doi: 10.1016/j.det.2018.05.009. PMID: 30201151
Fraitag S, Bodemer C
Curr Opin Pediatr 2010 Aug;22(4):438-44. doi: 10.1097/MOP.0b013e32833bc396. PMID: 20616730

Recent systematic reviews

Chen MKY, Flanagan AL, Sebaratnam DF, Gu Y
Australas J Dermatol 2024 Mar;65(2):185-214. Epub 2023 Dec 21 doi: 10.1111/ajd.14197. PMID: 38126177
Olbrich H, Sadik CD, Ludwig RJ, Thaçi D, Boch K
Biomolecules 2023 Mar 31;13(4) doi: 10.3390/biom13040634. PMID: 37189381Free PMC Article
Wu PC, Dai YX, Li CL, Chen CC, Chang YT, Ma SH
J Dtsch Dermatol Ges 2023 Jan;21(1):7-17. Epub 2023 Jan 19 doi: 10.1111/ddg.14924. PMID: 36657040
Nouwen AEM, Schappin R, Nguyen NT, Ragamin A, Bygum A, Bodemer C, Dalm VASH, Pasmans SGMA
Front Immunol 2022;13:864449. Epub 2022 Mar 30 doi: 10.3389/fimmu.2022.864449. PMID: 35464459Free PMC Article
Hernández-Martín A, González-Sarmiento R
Curr Opin Pediatr 2015 Aug;27(4):473-9. doi: 10.1097/MOP.0000000000000239. PMID: 26164154

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