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Disease Profile

Netherton syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Infancy

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ICD-10

Q80.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

NETH; Netherton disease

Categories

Congenital and Genetic Diseases; Eye diseases; Immune System Diseases;

Summary

Netherton disease is a rare disorder affecting the skin, hair and immune system. Symptoms are present at birth and include red, scaly skin. Other symptoms include outbreaks of red, circular scaly rashes, thin, fragile hair (bamboo hair), and immune reactions such as hay fever, asthma, itchy skin, and eczema. Dehydration and infection are common and can be serious. Babies tend to grow slowly and have poor weight gain. Netherton syndrome is caused by the SPINK5 gene not working correctly. It is inherited in an autosomal recessive pattern. Netherton syndrome is diagnosed based on clinical examination, the symptoms, and genetic testing. Treatment is focused on managing the symptoms.[1][2]

Symptoms

The following list includes the most common signs and symptoms in people with Netherton syndrome. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in Netherton syndrome.

Signs and symptoms include:[1][2]

The symptoms of Netherton syndrome are present at birth. Because the skin is abnormal, infants are at risk for dehydration and infections, both of which may be life-threatening. Growth and weight gain may be slow and individuals with this condition are often shorter than average. Over time, the skin symptoms often improve. Many individuals have periodic outbreaks of red, circular rashes. Some individuals with Netherton syndrome have developmental and intellectual delays. In addition, individuals with this condition have an increased susceptibility to get skin infections and to develop skin cancers in adulthood.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Acanthosis nigricans
Darkened and thickened skin
0000956
Asthma
0002099
Congenital nonbullous ichthyosiform erythroderma
0007479
Eczema
0000964
Fine hair
Fine hair shaft
Fine hair texture
Thin hair shaft
Thin hair texture

[ more ]

0002213
Increased circulating IgE level
0003212
Irregular hyperpigmentation
0007400
Malabsorption
Intestinal malabsorption
0002024
Sparse scalp hair
Reduced/lack of hair on scalp
Scalp hair, thinning
Sparse, thin scalp hair
sparse-absent scalp hair

[ more ]

0002209
Trichorrhexis nodosa
0009886
Urticaria
Hives
0001025
30%-79% of people have these symptoms
Decreased circulating antibody level
0004313
Emphysema
0002097
Global developmental delay
0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Seizure
0001250
5%-29% of people have these symptoms
Aminoaciduria
High urine amino acid levels
Increased levels of animo acids in urine

[ more ]

0003355
Dehydration
0001944
Dry skin
0000958
Ectopic kidney
Abnormal kidney location
Displaced kidney

[ more ]

0000086
Erythroderma
0001019
Hydronephrosis
0000126
Short stature
Decreased body height
Small stature

[ more ]

0004322
Skin rash
0000988
Sparse and thin eyebrow
Thin, sparse eyebrows
0000535
Sparse eyelashes
Scant eyelashes
Scanty eyelashes
Thin eyelashes

[ more ]

0000653
1%-4% of people have these symptoms
Intestinal atresia
0011100
Percent of people who have these symptoms is not available through HPO
Abnormality of the musculature
Muscular abnormality
0003011
Allergic rhinitis
Hay fever
Hayfever

[ more ]

0003193
Angioedema
0100665
Autosomal recessive inheritance
0000007
Brittle hair
0002299
Brittle scalp hair
0004779
Decreased circulating IgG level
0004315
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Food allergy
0500093
Hypereosinophilia
0032061
Hypernatremic dehydration
0004906
Parakeratosis
0001036
Recurrent infections
Frequent infections
Frequent, severe infections
Increased frequency of infection
infections, recurrent
Predisposition to infections
Susceptibility to infection

[ more ]

0002719
Villous atrophy
0011473

Cause

Netherton syndrome occurs when the SPINK5 gene is are not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[1]

Diagnosis

Netherton syndrome is diagnosed based on the symptoms and confirmed by genetic testing for changes in the SPINK5 gene. Other types of testing, such as close examination of the hair and a skin biopsy to obtain a small skin sample for examining under the microscope can also be helpful for diagnosis.[3]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Treatment

    There is no specific treatment for this condition. Treatment is aimed at preventing and/or managing the known symptoms and complications associated with this condition.[4]

    Specialists involved in the care of someone with Netherton syndrome include:

    • Dermatologist
    • Immunologist
    • Allergist
    • Medical geneticist

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
      • Genetics Home Reference (GHR) contains information on Netherton syndrome. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Netherton syndrome. Click on the link to view a sample search on this topic.

          References

          1. Sarri CA, Roussaki-Schulze A, Vasilopoulos Y, Zafiriou E, Patsatsi A, et al. Netherton Syndrome: A Genotype-Phenotype Review. Mol Diagn Therap. Apr, 2017; 21(2):137-152. www.ncbi.nlm.nih.gov/pubmed/27905021.
          2. Saleem HMK, Shahid MF, Shahbaz A, Schail A, Sachmechi I.. Netherton syndrome: A case report and review of the literature. Cureus. Jul 30, 2018; 10(7):e3070. www.ncbi.nlm.nih.gov/pubmed/30280066.
          3. Leclerc-Mercier S, Bodemer C, Furio L. Skin biopsy in Netherton syndrome: a histological review of a large series and new findings. Am J Dermatopathol. 2016; 38(20:83-91. www.ncbi.nlm.nih.gov/pubmed/26825155.
          4. Roda A, Mendonca-Sanches M, Travassos AR, Soares-de-Almeida L, Metze D. Infliximab therapy for Netherton syndrome: A case report. JAAD Case Rep. Nov 6, 2017; 3(6):550-552. www.ncbi.nlm.nih.gov/pubmed/29159247.
          5. Milestone LM, Miller K, Haberman M, Dickens J.. Incidence of moderate to severe ichthyosis in the United States.. Arch Dermatol. Sept 2012; 148(9):1080-1. www.ncbi.nlm.nih.gov/pubmed/22986871.

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