Ichthyosis linearis circumflexa, Comel Netherton syndrome, Axial osteosclerosis with bamboo hair, Netherton disease, Comèl-Netherton syndrome
Table of contents
- What is Netherton’s syndrome?
- Signs and symptoms
- What causes this condition?
- How common is it?
- How is it diagnosed?
- Treatment and management
- Living with Netherton’s syndrome
What is Netherton’s syndrome?
Netherton’s syndrome is a disorder that affects the skin, hair, and immune system. The condition is present at birth or appears during the first few weeks of life. It is a rare inherited disorder that requires lifelong management, though the severity of symptoms can vary greatly from person to person.[1]
Under normal circumstances, the skin acts as a barrier that maintains body temperature while keeping moisture in and infection out. In people with Netherton’s syndrome, this protective function is impaired, making the skin “leaky.” This leads to loss of heat, important proteins, and moisture, making affected individuals prone to infection.[2]
Signs and symptoms
Newborns with Netherton’s syndrome have skin that is red and scaly, a condition called ichthyosiform erythroderma (inflamed, red, scaly skin). The skin may leak fluid, and some affected infants are born with a tight, clear covering called a collodion membrane, which 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.[1]
At birth, babies with Netherton’s syndrome look as if they have been scalded, with their skin at its reddest during the first year of life. One of the key features is a failure to thrive, especially in the first two years of life. Growth and weight gain are usually significantly lower than that of children of a similar age, and individuals with Netherton’s syndrome tend to be of short stature.[6]
After infancy, the severity of the skin abnormalities varies 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 with a thickened horny margin and a slowly changing pattern. This condition usually occurs after 2 years of age and tends to go through bouts of flaring followed by months of no skin symptoms.[1][2]
People with Netherton’s 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—a ball-and-socket-type hair-shaft deformity. Most patients will grow sparse, abnormal hair that is short, spiky, lustreless, and brittle. In addition to the hair on the scalp, the eyelashes and eyebrows may be affected. Older patients may lose eyebrows and eyelashes altogether. The hair abnormality may not be noticed in infancy because babies often have sparse hair.[1][2]
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.[1]
Most people with Netherton’s syndrome have immune system-related problems such as food allergies (especially to nuts and fish), hay fever, asthma, or an inflammatory skin disorder called eczema. Patients have high levels of IgE (allergy antibody) in their blood and may suffer attacks of angioedema (severe allergic skin reaction) and urticaria.[1][2]
What causes this condition?
Netherton’s syndrome is caused by mutations in the SPINK5 gene. This gene provides instructions for making a protein called LEKT1, which is a type of serine peptidase inhibitor. Serine peptidase inhibitors control the activity of enzymes called serine peptidases, which break down other proteins.[1]
LEKT1 is found in the skin and in the thymus, 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.[1]
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 seen in Netherton’s syndrome.[1]
Netherton’s syndrome is inherited as an autosomal recessive trait. This means that the condition is revealed when two unaffected parents who are both carriers of the mutated recessive gene have a child who receives both copies of the recessive gene.[2]
How common is it?
Netherton’s syndrome is estimated to affect 1 in 200,000 newborns. Fewer than 5,000 people in the United States have this disease.[1][3]
How is it diagnosed?
Netherton’s syndrome should be at the top of the differential diagnosis list in a newborn with erythroderma (widespread reddening of the skin) and abnormal-looking scalp hair, or in an older child with ichthyosis linearis circumflexa and sparse lustreless hair.[2]
The diagnosis is based on clinical examination and symptoms. The skin will be red, especially for the first year of life, and will usually be rough or “scaly” and quite itchy at times.[6]
Examination of abnormal hair under a microscope shows trichorrhexis invaginata (defects of the hair shafts). This does not usually develop until after 2 years of age but may occur earlier. Some patients may appear to have normal-looking hair, but the hair shaft is abnormal under the microscope (subclinical trichorrhexis invaginata).[2]
Sometimes, a small piece of skin may be taken to do a skin biopsy to check for a protein called LEKT1; this will be missing in someone with Netherton’s syndrome. A skin biopsy is usually done by a dermatologist rather than a general practitioner or pediatrician.[6]
A blood test can also be taken (and sent to a national reference laboratory) to check for a fault in the SPINK5 gene through DNA testing.[2][6]
Often babies or children are not diagnosed for months or even years, as red skin at birth can be a symptom of other conditions, such as other types of ichthyosis, severe eczema, or other forms of immune deficiency.[6]
Treatment and management
There is no specific cure for Netherton’s syndrome. The goals of treatment are to manage the symptoms and prevent skin infections and other complications.[2]
It is common for babies with this condition to have to stay in a hospital incubator for a while to prevent dehydration or infection and allow their skin to be kept moist at all times. In very rare cases, newborns with particularly severe symptoms may not survive. The first year of life is the critical period, and some children are in and out of hospital with repeated infections, dehydration, and poor weight gain.[6]
Emollients (moisturizing products) and keratolytics (creams containing urea, lactic acid, or salicylic acid) should be applied to keep the skin moist and hydrated. Antibiotics may be used for skin infections. Topical steroids may be helpful in older children with eczema but can be absorbed too much in infants with erythroderma, causing complications such as pituitary adrenal axis suppression.[2]
Extra protein in the diet during childhood is beneficial to replace that which is lost through the “leaky” skin. Dead skin cells often accumulate in the ear canals, which can affect hearing if not removed regularly.[1][4]
Other treatments that have been tried include photochemotherapy (PUVA) and oral retinoids (acitretin and isotretinoin), but these may aggravate the skin. Steroid and retinoid products have been proven ineffective against Netherton’s syndrome in some cases and may in fact make things worse for the affected individual.[2][4]
Intravenous immunoglobulin has become established as a treatment option in some cases of Netherton’s syndrome, particularly when there are immune system-related complications.[4]
Living with Netherton’s syndrome
The health of older children and adults with Netherton’s 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’s syndrome and can fluctuate over time.[1]
As children get older, their skin tends to improve, although some people stay red all over, while others develop circular patches of red and scaly skin. The triggers for skin outbreaks are not known, but researchers suggest that stress or infections may be involved.[1][6]
Netherton’s syndrome is more than just a skin condition—it is a severe genetic disease that impacts every aspect of a person’s daily life. In addition to painful, scaly, and inflamed skin, individuals often experience complications of their immune function, growth, and overall health. These challenges frequently lead to frequent medical interventions, prolonged hospital stays, and emotional strain.[17]
People with this condition may experience ongoing psychological effects. Visible redness, patchy scales, and hair abnormalities can fuel self-consciousness, anxiety, and depression. Teens and adults may experience bullying, social withdrawal, or difficulty participating in sports and social events due to discomfort, overheating, or infection risk.[17]
Caregivers grapple with uncertain prognosis, frequent medical visits, and a scarcity of specialists familiar with Netherton’s syndrome. Feelings of helplessness and burnout are common when reliable, disease-modifying treatments remain unavailable.[17]
Daily routines often involve carefully monitored fluid intake and specialized skin care or anti-infective treatments. Despite these measures, infections and complications are common. A daily routine typically includes two showers a day, a whole lot of cream and medications, as well as antibiotics to keep any infection away. Skin goes through good days and bad days, which really changes how people tackle their routine.[12]
