Netherton syndrome is a rare genetic disorder that affects the skin, hair, and immune system. It is caused by mutations in the SPINK5 gene, which provides instructions for making a protein called LEKTI. LEKTI plays a crucial role in regulating the activity of enzymes called serine proteases, which are involved in many biological processes, including the development and maintenance of the skin barrier.

Distinctive Features

Netherton syndrome is characterized by three distinctive features: ichthyosiform erythroderma, trichorrhexis invaginata, and atopic diathesis. Ichthyosiform erythroderma is a type of skin inflammation that causes red, scaly patches on the skin, particularly on the scalp, face, and trunk. The skin may be itchy and prone to infections. Trichorrhexis invaginata, also known as ‘bamboo hair’, is a hair shaft abnormality that causes short, brittle, and easily broken hair that looks like bamboo shoots under the microscope. Atopic diathesis is a predisposition to allergic diseases, such as atopic dermatitis, asthma, and food allergies.

Clinical Features

The symptoms of Netherton syndrome can vary in severity and presentation, even among individuals with the same genetic mutation. In addition to the distinctive features, affected individuals may also experience recurrent infections, failure to thrive, and developmental delays.

Diagnosis

Netherton syndrome can be diagnosed upon the presence of the skin lesions, hair findings, family history of Netherton syndrome, or finding of SPINK5 mutation by DNA sequencing. Genetic testing and a skin biopsy could be helpful in confirming the diagnosis.

Management

Treatment of Netherton syndrome is mainly supportive, and aims to manage the symptoms and complications of the condition. Topical emollients, such as creams or ointments that contain lipids and humectants, can help to moisturize and protect the skin and prevent itching and scratching. Antihistamines, corticosteroids, or topical calcineurin inhibitors may be used to alleviate inflammation or itching. In severe cases, Intravenous immunoglobulin (IVIG) replacement therapy has led to improvement in some patients.

Future Research

Research on Netherton syndrome is ongoing, and several potential therapies are being investigated. One promising approach is the use of recombinant LEKTI, which could restore the normal regulation of serine proteases in the skin and improve the skin barrier function. Other strategies involve the modulation of specific inflammatory pathways or the transplantation of healthy skin cells.

Written by

Deemah AlHuraish, Medical Student

References

UpToDate

DermNet