Netherton syndrome

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What is Netherton syndrome?

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.

How common is Netherton syndrome?

Netherton syndrome is estimated to affect 1 in 200,000 newborns.

What genes are related to Netherton syndrome?

Netherton syndrome is caused by mutations in the SPINK5 gene. This gene provides instructions for making a protein called LEKT1. LEKT1 is a type of serine peptidase inhibitor. Serine peptidase inhibitors control the activity of enzymes called serine peptidases, which break down other proteins. LEKT1 is found in the skin and in the thymus, which is a gland located behind the breastbone that plays an important role in the immune system by producing white blood cells called lymphocytes. LEKT1 controls the activity of certain serine peptidases in the outer layer of skin (the epidermis), especially the tough outer surface known as the stratum corneum, which provides a sturdy barrier between the body and its environment. Serine peptidase enzymes are involved in normal skin shedding by helping to break the connections between cells of the stratum corneum. LEKT1 is also involved in normal hair growth, the development of lymphocytes in the thymus, and the control of peptidases that trigger immune system function.

Mutations in the SPINK5 gene result in a LEKT1 protein that is unable to control serine peptidase activity. The lack of LEKT1 function allows the serine peptidases to be abnormally active and break down too many proteins in the stratum corneum. As a result, too much skin shedding takes place, and the stratum corneum is too thin and breaks down easily, resulting in the skin abnormalities that occur in Netherton syndrome. Loss of LEKT1 function also results in abnormal hair growth and immune dysfunction that leads to allergies, asthma, and eczema.

How do people inherit Netherton syndrome?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of Netherton syndrome?

These resources address the diagnosis or management of Netherton syndrome and may include treatment providers.

Genetic Testing Registry: Netherton syndrome

You might also find information on the diagnosis or management of Netherton syndrome in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about Netherton syndrome?

You may find the following resources about Netherton syndrome helpful. These materials are written for the general public.

MedlinePlus - Health information (5 links)
Educational resources - Information pages (4 links)
Patient support - For patients and families (4 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Genetic Testing Registry - Repository of genetic test information (1 link)
ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature
OMIM - Genetic disorder catalog

What other names do people use for Netherton syndrome?

bamboo hair syndrome
Comel-Netherton syndrome
ichthyosiform erythroderma with hypotrichosis and hyper-IgE
ichthyosis linearis circumflexa
ILC
NETH
Netherton disease
NS

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about Netherton syndrome?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding Netherton syndrome?

autosomal ; autosomal recessive ; cell ; diameter ; eczema ; epidermis ; erythroderma ; failure to thrive ;fever ; gene ; hypotrichosis ; ichthyosiform ; ichthyosis ; immune system ; protein ; recessive ; sepsis ;serine ; short stature ; stature ; stress ; syndrome ; thymus ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (7 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.