Netherton’s Syndrome: A Case of Two Male Siblings Diagnosed in Adulthood

Abstract

Netherton's syndrome (NS) is a rare autosomal recessive genetic disease caused by a germline mutation in the SPINK5 gene. It is most commonly diagnosed in neonates due to the presence of congenital ichthyosiform erythroderma. Affected individuals will typically also develop a hair shaft abnormality known as trichorrhexis invaginata, severe atopy, and a migratory rash known as ichythyosis linearis circumflexa. The chronicity and severity of NS adversely affects a patient's quality of life to a large extent. It Is therefore important that this condition is identified early, and treatment to reduce cutaneous inflammation is initiated in a timely fashion. However, due to this condition being relatively rare, a lack of awareness may lead clinicians to misdiagnose it as atopic dermatitis or undifferentiated psoriasis. Clinicians should therefore be aware of the peripheral stigmata that this disease may present as in adulthood, so that a correct diagnosis can be made if it was previously missed. Here we present a case of two male siblings from Jordon who were misdiagnosed since childhood as having erythrodermic psoriasis. Clinical examination of one of the siblings, as an adult, revealed multiple peripheral features associated with NS. Genetic analysis through sanger sequencing was also able to identify a mutation in the SPINK5 gene, confirming the diagnosis.

Trichorrhexis invaginata and ichthyosiform erythroderma in netherton syndrome

“…Histopathological examination from the child’s skin revealed psoriasiform dermatitis capable with innate lymphoid cells and genetic analysis confirmed the Netherton syndrome diagnosis. 1 , 2 …”

A novel mutation in SPINK5 gene underlies a case of atypical Netherton syndrome

“…NS is caused by a loss-of-function mutation of SPINK5 (serine protease inhibitor of Kazal type 5) on chromosome 5q31-32 that encodes a lymphoepithelial Kazal-type related inhibitor (LEKTI) (Sarri et al, 2017;Herz-Ruelas et al, 2021). The LEKTI plays a critical role in maintaining skin barrier function and regulating the desquamation of keratinocytes (Chavanas et al, 2000;Flora and Smith, 2020). Currently, there is no cure or satisfactory treatments for NS.…”