Netherton syndrome ... (Netherton syndrome) - Gen SPINK5.

Netherton syndrome is a disorder that affects the skin, hair, and the immune system with a high risk for allergies, asthma and eczema.

Signs and symptoms of the disease in newborns can include redness, scaly skin, and growth retardation. Because newborns with the disease lose the protection afforded by normal skin, they are at risk of becoming dehydrated and develop skin infections or any part of the body, which can be fatal. After infancy, the severity of skin abnormalities varies between individuals affected and may fluctuate over time. The skin may remain red and scaly, especially during the first years of life. Some affected individuals have redness or have intermittent outbreaks of ichthyosis linearis circumflexa, with the appearance of multiple lesions in a ring. Triggers the outbreaks are not known, but it is believed that could be triggered by stress or infection. Itching is a common problem in people affected, and scratching can trigger frequent infections. Furthermore, dead skin cells are shed abnormal rhythm and often accumulate in the ear canals, and may affect hearing if not removed regularly. Additionally, the skin absorbs abnormally substances such as lotions and ointments, which can cause high blood concentrations of some topical medications are achieved.

People with the syndrome have fragile and brittle hair. Some strands of hair vary in diameter, with areas of thick hair and other thin hair. This alteration is known as bamboo hair, trichorrhexis nodosa or invaginata trichorrhexis. In addition to the scalp hair they may be affected eyelashes and eyebrows. Most people with Netherton syndrome have problems with the immune system , such as food allergies, hay fever, asthma, eczema or system. The health of those affected usually improves, although they often remain with weight and short stature.

Netherton syndrome is caused by mutations in the gene SPINK5, located on the long arm of chromosome (5q32), encoding the protein LEKT1, a type of serine peptidase inhibitor. Inhibitors of serine peptidase control the activity of peptidases serine enzymes that break down other proteins. The protein is found in the skin and thymus, controls the activity of serine peptidases certain in the epidermis, particularly the stratum corneum, which provides a resistive barrier between the organism and its surroundings. The peptidase serine enzymes are involved in the normal change of the skin, helping to break the connections between the cells of the stratum corneum. LEKT1 is also involved in normal hair growth, cell development in the thymus, and control peptidase activate the immune system function.

They have identified at least 70 SPINK5 mutations in the gene cause the disease. These changes result in a protein LEKT1 is unable to control the activity of serine peptidases. The lack of protein function causes the -peptidasas serine are abnormally active and decompose many proteins in the stratum corneum. As a result, excessive loosening of the skin occurs, causing the stratum corneum is unusually thin and break easily. LEKT1 function loss also results in abnormal hair growth and immune dysfunction that leads to allergies, asthma and eczema.

Netherton syndrome is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Netherton syndrome by complete PCR amplification of the exons of the gene SPINK5, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).