Netherton Syndrome

What is Netherton Syndrome?

Netherton Syndrome is an autosomal recessive disorder involve the hereditary transmission of the condition, characterized by three clinical presentations – ichthyosiform erythroderma; trichorrhexis invaginata and atopic diathesis.

All the clinical presentations may or may not be present, which mainly depend upon the severity of the disease¹.

Predominance

Netherton syndrome is considered as a rare disorder and in has been estimated that the incidence of this condition is 1 in 200,000 infants².

Symptoms

The symptoms of Netherton Syndrome usually observable at the time of birth or within initial weeks after the birth of the neonates.

A wide extended red colored skin with a dry scaly texture covers almost all body area. At the late childhood eczematous rash may also present. The dermatological condition leads to “leaky” skin and essential elements like water, protein, and heat excreted from the body. This interferes the growth retardation of the neonates.

Neonates are having a high risk of infection due to compromised immunity and that can result in fatal outcome. Severe infection often has poor prognosis.

In the case of mild to moderate infection, infants unable to completely thrive in the first year of life; but gradually improve their health in the subsequent years. However, affected children usually have short stature and remain underweight.

The three classic clinical presentations of Netherton Syndrome are as follows:

Ichthyosiform Erythroderma: This is a distinct skin condition in which body is covered with a circular scaly skin. This symptom appears after 2 years of age of the affected children. After arising from the condition, initial flaring continues for a short duration, then diminish

This will follow no skin symptoms in the subsequent months. The circular pattern rashes have thick horny margin and gradually change the pattern.

Trichorrhexis invaginata (“bamboo hair”): The quality of the hair is compromised and affected children usually have thorny, short, brittle and lusterless. The hair shafts also have a ball-and-socket-type deformity. Eyebrows and eyelashes are lost with increasing age.

However, some affected individual has normal appearance of hair externally, but the microscopic analysis can evaluate the abnormality.

Atopic diathesis – This is a type of allergic manifestation and affected children have a tendency to develop a food allergy. Usually, allergy in nuts is a common condition and that leads to asthma, hay fever, and atopic eczema.

This allergic manifestation develops due to increasing level of IgE in the blood. In severe condition, angioderma and urticaria are the skin reactions occur^2,3.

Causes

Netherton syndrome is a resultant of abnormal genetic mutation involves SPINK5 gene. SPINK5 gene is present on chromosome 5 (5q32) on the long arm (q). The genetic mutation transmission is conducted through autosomal recessive inheritance.

The affected children receive two recessive mutated genes from each parent and therefore inherit involvement is present in Netherton syndrome. In the case of inheriting the condition, parents act as carriers.

The encoding protein of SPINK5 gene has to hold activity of certain enzymes involve in protein digestion (proteases) and maintain the protein made anatomical structures. The abnormal genetic mutation of SPINK5 gene causes damage of the skin layers and only a few layers cover the outer skin and resultant of this leads to Ichthyosiform Erythroderma^1,3,4.

 

Diagnosis

If an infant has any of the classic clinical presentation at the time of birth or recently after birth, then the differential diagnosis conducted for Netherton syndrome.

Microscopic hair analysis can detect detective hair shafts, clinically that reported as trichorrhexis invaginata. But this can be detected after two years of the affected child because the symptomatic approach develops after two years.

For confirmation, some experts also recommended genetic testing and to understand the genetic complications skin biopsy and DNA testing require to conduct³.

Treatment

Netherton syndrome has no specific treatment, but the treatment goal is to provide symptomatic relief of the patient. The treatment plan is usually customized depending upon the patient’s condition and to prevent related complications. The following recommendation usually made by the medical team to lessen the discomfort and severity of the condition.

• Topical application of emollient for softening the skin and keratolytic for smoothing the skin surface are helpful to keep the skin hydrated by maintaining the moisture content. Usually, the active constituents of these emollient and keratolytic creams are urea, lactic acid or salicylic acid.
• Antibiotics are prescribed to treat infection if present in the skin
• Steroidal creams also topically applied in children with older age to control eczema. But the dose and duration of the steroidal treatment are considerably important to control erythroderma, because it may cause suppression of pituitary adrenal axis.
• PUVA or Photochemotherapy and acitretin and isotretinoin are the oral retinoids may apply to treat Netherton syndrome related skin disorder, but treatment plan needs to conduct carefully to avoid the aggravation of the skin problem.

In most of the cases, Netherton syndrome-related symptoms are minimized with increasing age of the child. There is no evidence that intermittent exacerbations influence the duration or expansion of the Netherton syndrome symptoms. But it is expected that Netherton syndrome may influence skin cancer incidence^3,4.

Prognosis

The complications arise due to Netherton syndrome causes postnatal lethality. The skin and hair related problems continue for life-long. However, normal health condition usually arises after second years of the life².

Life Expectancy

Netherton syndrome life expectancy is not same for every affected individual If the child gets good to thrive after 2 years of age without complicated health condition, then they may lead normal expectancy, but the incidence of severe infection or other complications like skin cancer may have compromised life expectancy⁵.

References

1. Laura F McGevna. Trichorrhexis Invaginata (Netherton Syndrome or Bamboo Hair). http://emedicine.medscape.com/article/1071656-overview
2. Vanessa Ngan. Netherton syndrome.  DermNet NZ. http://www.dermnetnz.org/topics/netherton-syndrome/
3. Ichthyosis, Netherton Syndrome. National Organization For Rare Disorder. https://rarediseases.org/rare-diseases/ichthyosis-netherton-syndrome/
4. Netherton syndrome. Genetic Home Reference. https://ghr.nlm.nih.gov/condition/netherton-syndrome#diagnosis
5. Netherton syndrome. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=634