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Ichthyosis, Netherton Syndrome

NORD is very grateful to the members of the Medical and Scientific Advisory Board of the Foundation for Ichthyosis & Related Skin Types for assistance in the preparation of this report.

Synonyms of Ichthyosis, Netherton Syndrome

  • Comel-Netherton Syndrome
  • Ichthyosis Linearis Circumflexa

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Netherton syndrome is a rare hereditary disorder characterized by scaling skin, hair anomalies, increased susceptibility to atopic eczema (a skin condition that can result in dry, red and flaky skin), elevated IgE levels, and other related symptoms. Netherton syndrome is inherited as an autosomal recessive trait.

Symptoms

Newborns with Netherton syndrome have reddened skin (erythroderma) and sometimes a thick parchment-like covering of skin (collodion membrane). The skin is red and scaly all over. Hair shafts are fragile and break easily due to trichorrhexis or "bamboo hair", resulting in short sparse hair. In older children and adults the scaling may have a distinctive circular pattern (ichthyosis linearis circumflexa). Another characteristic of Netherton syndrome is a predisposition to allergies, asthma, and eczema.

Babies with Netherton syndrome may be born prematurely. Trouble gaining weight in infancy and childhood is common and can be severe. Infants may also have recurrent skin infections and septicemia. They may develop hypernatremia (elevated sodium levels in the blood) due to excessive loss of fluid from the skin surface. Because hairs may not be affected at birth, and then may be sparse in all babies in the first months of life, the characteristic hair defect that is diagnostic of Netherton syndrome may not be detected initially.

Infants with Netherton syndrome may be misdiagnosed as having CIE (congenital ichthyosiform erythroderma), atopic dermatitis or psoriasis. Atopic dermatitis (red, itchy patches of skin) may be present and a cradle cap-like scale and redness may appear on the face, scalp and eyebrows.

Causes

The mutation that causes Netherton syndrome has been pinpointed to the gene SPINK5 located on the long arm (q) of chromosome 5 (5q32). This mutation is transmitted by autosomal recessive inheritance. Individuals must inherit two recessive genes in order to show the disorder, with each parent donating one mutated gene. The parents (carriers) show no evidence of Netherton syndrome.

The SPINK5 gene encodes a protein that serves as the brake on the activity of certain proteases (enzymes that digest proteins) in the skin protein. Increased protease action in the skin results in too few layers of the outer skin (stratum corneum), not in too many layers as in other forms of ichthyosis.

Affected Populations

Netherton syndrome is a rare hereditary disorder. There are approximately 150 cases reported in the medical literature, but the true number of affected individuals may be much higher due to diagnostic difficulties and overlapping symptoms with common atopic dermatitis and other congenital ichthyoses.

Related Disorders

Symptoms of the following disorders may be similar to those of Netherton syndrome. Comparisons can be useful for a differential diagnosis.

Ichthyoses or "disorders of cornification" are general terms describing a group of scaly skin disorders. They are characterized by an abnormal accumulation of large amounts of dead skin cells (squames) in the top layer of the skin. The conversion of an abnormally large number of epidermal cells into squamous cells is thought to be caused by a defect in the metabolism of the skin cells known as "corneocytes" or the fat-rich matrix around these cells. These cells can be thought of as bricks, while the matrix would be the mortar holding these cells together. (See "Ichthyosis" in the Rare Disease Database.)

Ichthyosis congenita (collodion baby; congenital ichthyosiform erythroderma; xeroderma; desquamation of the newborn) is an inherited skin disorder. It is characterized by generalized, abnormally red, dry, and rough skin with large coarse and fine white scales. Itchiness (pruritus) usually also develops. Skin on the palms of the hands and soles of the feet can be abnormally thick. (For more information, choose "Ichthyosis Congenita" as your search term in the Rare Disease Database.)

X-linked ichthyosis is an inherited skin disorder that affects males. It is caused by a deficiency of the enzyme steroid sulfatase. It is characterized by brownish scales on the back of the neck, back and legs.

Standard Therapies

The treatment of Netherton syndrome is symptomatic, often difficult, and should be tailored to the patient's specific needs. Recommendations include the regular use of emollients and moisturizing creams and lotions. Other topical agents should be used with caution because the skin in Netherton syndrome may allow ingredients from some topically applied medications to be absorbed into the blood, which may pose a danger to the child. Topical keratolytic agents such as urea or lactic acid derivatives may be limited by skin irritation and should generally be reserved for older children. The base line treatment also includes oral antihistamines, which can help to control the itchy, eczematous component, and topical or systemic antibiotics as needed. To treat the scaling of the scalp, mild dandruff shampoos and topical steroids might be helpful. Oral and topical steroids are beneficial in reducing inflammation and the eczematous component of the disease. However, the well-documented side effects of long-term steroid use need to be considered. Oral retinoids have been used with varying success, leading to dramatic improvement in some patients and severe worsening of the disease in others.

Molecular Diagnostic testing for Netherton syndrome is offered by:

Gabriele Richard, MD
Associate Professor, Department of Dermatology and Cutaneous Biology and
Department of Medicine / Division of Medical Genetics
Thomas Jefferson Unversity
233 S. 10th. Street, BLSB Suite 409
Philadelphia, PA 19107
Telephone: ( 215) 503-8259 (lab)
Fax: (215) 503-5788
Email: Gabriele.Richard@jefferson.edu

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Researchers have studied the use of calcipotriol, a vitamin D derivative, as a potential treatment for individuals with Netherton syndrome. In one case, the initial results demonstrated improvement of erythema and scaling and no adverse effects. More research is necessary to determine the long-term safety and effectiveness of this potential treatment for Netherton syndrome.

Ichthyosis, Netherton Syndrome Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:

References

JOURNAL ARTICLES
Chao SC, Richard G, Lee JY. Netherton syndrome: report of two Taiwanese siblings with staphylococcal scalded skin syndrome and mutation of SPINK5. Br J Dermatol. 2005:152:159-65.

Godic A, Dragos V. Successful treatment of Netherton's syndrome with topical calcipotriol. Eur J Dermatol. 2004:14:115-7.

Sprecher, E, et al. The spectrum of pathogenic mutations in SPINK5 in 19 families with Netherton Syndrome: Implications for mutation detection and first case of prenatal diagnosis. J Invest Dermatol. 2001; 117(2): 179-187.

Chavanas, S, et al. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton Syndrome. Nat Genet. 2000; 25: 141-142.

Judge, MR, Morgan , G, Harper, JI. A clinical and immunological study of Netherton's syndrome. Br J Dermatol. 1994; 131: 615-21.

Williams, ML, et al. Genetically Transmitted, Generalized Disorders of Cornification. The Ichthyoses. Dermatol Clin. January 1987; 5(1): 155-78.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2008/04/11 00:00:00 GMT+0

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