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Netherton syndrome(NETH)

MedGen UID:
78578
Concept ID:
C0265962
Congenital Abnormality; Disease or Syndrome
Synonyms: COMEL-NETHERTON SYNDROME; ERYTHRODERMA, ICHTHYOSIFORM, WITH HYPOTRICHOSIS AND HYPER-IgE; Ichthyosis linearis circumflexa; NETH; Netherton disease
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, 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 homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Netherton's syndrome (312514006); Comel-Netherton syndrome (312514006); Axial osteosclerosis with bamboo hair (312514006); Netherton syndrome (312514006); Lamellar ichthyosis AND trichorrhexis invaginata syndrome (34638006); Netherton's disease (34638006); Ichthyosis linearis circumflexa (54336006)
 
Gene (location): SPINK5 (5q32)
OMIM®: 256500
Orphanet: ORPHA634

Definition

Netherton syndrome 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 GTR]

Additional descriptions

From OMIM
Netherton syndrome 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).  http://www.omim.org/entry/256500
From GHR
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.After infancy, the severity of the skin abnormalities varies among people with Netherton syndrome and can fluctuate over time. The skin may continue to be red and scaly, especially during the first few years of life. Some affected individuals have intermittent redness or experience outbreaks of a distinctive skin abnormality called ichthyosis linearis circumflexa, involving patches of multiple ring-like lesions. The triggers for the outbreaks are not known, but researchers suggest that stress or infections may be involved.Itchiness is a common problem for affected individuals, and scratching can lead to frequent infections. Dead skin cells are shed at an abnormal rate and often accumulate in the ear canals, which can affect hearing if not removed regularly. The skin is abnormally absorbent of substances such as lotions and ointments, which can result in excessive blood levels of some topical medications. Because the ability of the skin to protect against heat and cold is impaired, affected individuals may have difficulty regulating their body temperature.People with Netherton syndrome have hair that is fragile and breaks easily. Some strands of hair vary in diameter, with thicker and thinner spots. This feature is known as bamboo hair, trichorrhexis nodosa, or trichorrhexis invaginata. In addition to the hair on the scalp, the eyelashes and eyebrows may be affected. The hair abnormality in Netherton syndrome may not be noticed in infancy because babies often have sparse hair.Most people with Netherton syndrome have immune system-related problems such as food allergies, hay fever, asthma, or an inflammatory skin disorder called eczema.  https://ghr.nlm.nih.gov/condition/netherton-syndrome

Clinical features

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.
Urticaria
MedGen UID:
22587
Concept ID:
C0042109
Disease or Syndrome
A raised, erythematous papule or cutaneous plaque, usually representing short-lived dermal edema
Failure to thrive
MedGen UID:
115900
Concept ID:
C0231246
Finding
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Villous atrophy
MedGen UID:
892490
Concept ID:
C4020747
Finding
The enteric villi are atrophic or absent.
Cognitive delay
MedGen UID:
351243
Concept ID:
C1864897
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.
Ige, elevated level of
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased level of immunoglobulin E in blood.
Asthma
MedGen UID:
2109
Concept ID:
C0004096
Disease or Syndrome
A chronic respiratory disease manifested as difficulty breathing due to the narrowing of bronchial passageways.
Abnormality of the musculature
MedGen UID:
867380
Concept ID:
C4021745
Anatomical Abnormality
Abnormality originating in one or more muscles, i.e., of the set of muscles of body.
Asthma
MedGen UID:
2109
Concept ID:
C0004096
Disease or Syndrome
A chronic respiratory disease manifested as difficulty breathing due to the narrowing of bronchial passageways.
Erythroderma
MedGen UID:
3767
Concept ID:
C0011606
Disease or Syndrome
A generalized inflammatory cutaneous disorder characterized by erythema and desquamation.(NICHD)
Ige, elevated level of
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased level of immunoglobulin E in blood.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
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.
Ige, elevated level of
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased level of immunoglobulin E 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.
Sparse and thin eyebrow
MedGen UID:
371332
Concept ID:
C1832446
Finding
Decreased density/number and/or decreased diameter of eyebrow hairs.
Sparse scalp hair
MedGen UID:
346499
Concept ID:
C1857042
Finding
Decreased number of head hairs per unit area.
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.
Erythroderma
MedGen UID:
3767
Concept ID:
C0011606
Disease or Syndrome
A generalized inflammatory cutaneous disorder characterized by erythema and desquamation.(NICHD)
Urticaria
MedGen UID:
22587
Concept ID:
C0042109
Disease or Syndrome
A raised, erythematous papule or cutaneous plaque, usually representing short-lived dermal edema
Congenital nonbullous ichthyosiform erythroderma
MedGen UID:
38180
Concept ID:
C0079154
Disease or Syndrome
A chronic, congenital ichthyosis inherited as an autosomal recessive trait. Infants are usually born encased in a collodion membrane which sheds within a few weeks. Scaling is generalized and marked with grayish-brown quadrilateral scales, adherent at their centers and free at the edges. In some cases, scales are so thick that they resemble armored plate.
Brittle hair
MedGen UID:
120480
Concept ID:
C0263490
Disease or Syndrome
Fragile, easily breakable hair, i.e., with reduced tensile strength.
Sparse and thin eyebrow
MedGen UID:
371332
Concept ID:
C1832446
Finding
Decreased density/number and/or decreased diameter of eyebrow hairs.
Sparse scalp hair
MedGen UID:
346499
Concept ID:
C1857042
Finding
Decreased number of head hairs per unit area.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVNetherton syndrome
Follow this link to review classifications for Netherton syndrome in Orphanet.

Recent clinical studies

Etiology

Small AM, Cordoro KM
Pediatr Dermatol 2016 May;33(3):e222-3. Epub 2016 Apr 18 doi: 10.1111/pde.12856. PMID: 27086664
Hannula-Jouppi K, Laasanen SL, Ilander M, Furio L, Tuomiranta M, Marttila R, Jeskanen L, Häyry V, Kanerva M, Kivirikko S, Tuomi ML, Heikkilä H, Mustjoki S, Hovnanian A, Ranki A
JAMA Dermatol 2016 Apr;152(4):435-42. doi: 10.1001/jamadermatol.2015.5827. PMID: 26865388
Leclerc-Mercier S, Bodemer C, Furio L, Hadj-Rabia S, de Peufeilhoux L, Weibel L, Bursztejn AC, Bourrat E, Ortonne N, Molina TJ, Hovnanian A, Fraitag S
Am J Dermatopathol 2016 Feb;38(2):83-91. doi: 10.1097/DAD.0000000000000425. PMID: 26825155
Guerra L, Fortugno P, Sinistro A, Proto V, Zambruno G, Didona B, Castiglia D
J Dermatol 2015 Aug;42(8):786-94. Epub 2015 Apr 28 doi: 10.1111/1346-8138.12913. PMID: 25917539
Igawa S, Kishibe M, Honma M, Murakami M, Mizuno Y, Suga Y, Seishima M, Ohguchi Y, Akiyama M, Hirose K, Ishida-Yamamoto A, Iizuka H
J Dermatol Sci 2013 Oct;72(1):54-60. Epub 2013 Jun 1 doi: 10.1016/j.jdermsci.2013.05.004. PMID: 23810772

Diagnosis

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
Small AM, Cordoro KM
Pediatr Dermatol 2016 May;33(3):e222-3. Epub 2016 Apr 18 doi: 10.1111/pde.12856. PMID: 27086664
Yalcin AD
Immunopharmacol Immunotoxicol 2016;38(2):162-6. Epub 2015 Nov 23 doi: 10.3109/08923973.2015.1115518. PMID: 26592187
Guerra L, Fortugno P, Pedicelli C, Mazzanti C, Proto V, Zambruno G, Castiglia D
Acta Derm Venereol 2015 Jul;95(6):720-4. doi: 10.2340/00015555-2075. PMID: 25710899
Mendiratta V, Yadav P, Chander R, Aggarwal S
Pediatr Dermatol 2015 Jan-Feb;32(1):147-8. Epub 2014 Dec 2 doi: 10.1111/pde.12445. PMID: 25440527

Therapy

Tiryakioğlu NO, Önal Z, Saygili SK, Önal H, Ersoy Tunali N
Int J Dermatol 2017 Jan;56(1):106-108. Epub 2016 Feb 17 doi: 10.1111/ijd.13248. PMID: 26889743
Small AM, Cordoro KM
Pediatr Dermatol 2016 May;33(3):e222-3. Epub 2016 Apr 18 doi: 10.1111/pde.12856. PMID: 27086664
Yalcin AD
Immunopharmacol Immunotoxicol 2016;38(2):162-6. Epub 2015 Nov 23 doi: 10.3109/08923973.2015.1115518. PMID: 26592187
Aydın BK, Baş F, Tamay Z, Kılıç G, Süleyman A, Bundak R, Saka N, Özkaya E, Güler N, Darendeliler F
Pediatr Dermatol 2014 Jan-Feb;31(1):90-4. Epub 2013 Sep 9 doi: 10.1111/pde.12220. PMID: 24015757
Di WL, Mellerio JE, Bernadis C, Harper J, Abdul-Wahab A, Ghani S, Chan L, Martinez-Queipo M, Hara H, McNicol AM, Farzaneh F, McGrath J, Thrasher A, Qasim W
Hum Gene Ther Clin Dev 2013 Dec;24(4):182-90. doi: 10.1089/humc.2013.195. PMID: 24329107

Prognosis

Small AM, Cordoro KM
Pediatr Dermatol 2016 May;33(3):e222-3. Epub 2016 Apr 18 doi: 10.1111/pde.12856. PMID: 27086664
Hannula-Jouppi K, Laasanen SL, Ilander M, Furio L, Tuomiranta M, Marttila R, Jeskanen L, Häyry V, Kanerva M, Kivirikko S, Tuomi ML, Heikkilä H, Mustjoki S, Hovnanian A, Ranki A
JAMA Dermatol 2016 Apr;152(4):435-42. doi: 10.1001/jamadermatol.2015.5827. PMID: 26865388
Leclerc-Mercier S, Bodemer C, Furio L, Hadj-Rabia S, de Peufeilhoux L, Weibel L, Bursztejn AC, Bourrat E, Ortonne N, Molina TJ, Hovnanian A, Fraitag S
Am J Dermatopathol 2016 Feb;38(2):83-91. doi: 10.1097/DAD.0000000000000425. PMID: 26825155
Israeli S, Sarig O, Garty BZ, Indelman M, Bergman R, Sprecher E, Goldberg I
Dermatology 2014;228(2):183-8. Epub 2014 Feb 27 doi: 10.1159/000357560. PMID: 24577329
Diociaiuti A, Castiglia D, Fortugno P, Bartuli A, Pascucci M, Zambruno G, El Hachem M
Pediatr Dermatol 2013 Jul-Aug;30(4):e65-7. Epub 2013 Jan 17 doi: 10.1111/pde.12076. PMID: 23331056

Clinical prediction guides

Leclerc-Mercier S, Bodemer C, Furio L, Hadj-Rabia S, de Peufeilhoux L, Weibel L, Bursztejn AC, Bourrat E, Ortonne N, Molina TJ, Hovnanian A, Fraitag S
Am J Dermatopathol 2016 Feb;38(2):83-91. doi: 10.1097/DAD.0000000000000425. PMID: 26825155
Israeli S, Sarig O, Garty BZ, Indelman M, Bergman R, Sprecher E, Goldberg I
Dermatology 2014;228(2):183-8. Epub 2014 Feb 27 doi: 10.1159/000357560. PMID: 24577329
van Smeden J, Janssens M, Boiten WA, van Drongelen V, Furio L, Vreeken RJ, Hovnanian A, Bouwstra JA
J Invest Dermatol 2014 May;134(5):1238-1245. Epub 2013 Nov 29 doi: 10.1038/jid.2013.517. PMID: 24292773
Bonnart C, Deraison C, Lacroix M, Uchida Y, Besson C, Robin A, Briot A, Gonthier M, Lamant L, Dubus P, Monsarrat B, Hovnanian A
J Clin Invest 2010 Mar;120(3):871-82. Epub 2010 Feb 22 doi: 10.1172/JCI41440. PMID: 20179351Free PMC Article
Yan AC, Honig PJ, Ming ME, Weber J, Shah KN
Arch Dermatol 2010 Jan;146(1):57-62. doi: 10.1001/archdermatol.2009.326. PMID: 20083693

Recent systematic reviews

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
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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