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Year : 2022  |  Volume : 23  |  Issue : 2  |  Page : 175-176

Netherton syndrome presenting with persistent pneumonia in a newborn

1 Department of Fetal Medicine and Genetics; Department of Neonatology, Fernandez Hospital, Hyderabad, Telangana, India
2 Department of Neonatology, Fernandez Hospital, Hyderabad, Telangana, India

Date of Submission06-Apr-2021
Date of Decision23-Nov-2021
Date of Acceptance26-Dec-2021
Date of Web Publication30-Mar-2022

Correspondence Address:
Dr. Gayatri Nerakh
Department of Fetal Medicine and Genetics, Fernandez Hospital, Hyderabad, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpd.ijpd_163_21

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How to cite this article:
Nerakh G, Nadipineni R, Rajeev P S, Oleti T. Netherton syndrome presenting with persistent pneumonia in a newborn. Indian J Paediatr Dermatol 2022;23:175-6

How to cite this URL:
Nerakh G, Nadipineni R, Rajeev P S, Oleti T. Netherton syndrome presenting with persistent pneumonia in a newborn. Indian J Paediatr Dermatol [serial online] 2022 [cited 2022 May 20];23:175-6. Available from: https://www.ijpd.in/text.asp?2022/23/2/175/341465


Netherton syndrome (OMIM #256500) is a rare autosomal recessive skin disorder caused due to pathogenic variants in the SPINK5 gene. It is characterized by a triad of congenital ichthyosiform erythroderma, hair shaft abnormalities, and atopic diathesis.[1] Its incidence worldwide is estimated to be 1 in 200,000. Mutations in the SPINK5 gene results in dysregulation of epidermal proteases, premature degradation of corneodesmosome, and thinning of stratum corneum resulting in the disease phenotype.[2]

A preterm neonate born second to healthy fifth-degree consanguineous couple had ichthyosiform erythroderma at birth. Baby had severe respiratory distress and was ventilated. On examination, there was sparse, easily pluckable scalp hair with no facial dysmorphism. The skin was dry, erythematous initially [Figure 1], later on, had ichthyosis linearis circumflexa (ILC) [Figure 2] and dry, scaly icthyosis [Figure 3] with superficial gangrene of the left forearm. Nails were normal. Systemic examination was normal. Chest X-rays showed persistent right-sided pneumonic nonresolving opacities [Figure 4] even after systemic antibiotics. The immunology panel revealed mildly elevated IgE levels (103.6 IU/mL). Complete blood picture showed anemia, low lymphocytes (14%–23%) with coagulopathy. Serum electrolytes revealed hypernatremia. Blood culture was positive for staphylococcus hemolyticus on day 7. Skin biopsy showed staphylococci colonization in deeper layers of the dermis. Hair microscopy was unremarkable. Two-dimensional ECHO, ultrasound abdomen were normal.
Figure 1: Congenital ichthyosiform erythroderma

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Figure 2: Ichthyosis linearis circumflexa

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Figure 3: Ichthyosis with dry, scaly skin

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Figure 4: Persistent right-sided pneumonic opacities

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The neonate, later on, had diarrhea, failure to thrive, and succumbed at the age of 1 month. Clinical exome sequencing revealed a homozygous pathogenic variant c.410+1G>A (5'splice site) in intron 5 of SPINK5 gene known to cause Netherton syndrome, which was consistent with the diagnosis of the neonate.

Clinical presentation and the complications of Netherton syndrome are often more severe during infancy and childhood than in adulthood. Congenital ichthyosiform erythroderma which will present at birth later evolve into ILC followed by dry, scaly ichthyosis. The hairs are typically sparse, dry, and brittle. The hair shaft abnormality is pathognomonic with trichorrhexis invaginata/nodosa under light microscopic examination or characteristic band-like hair patterns under polarized light.[3] Although hair shaft abnormality is pathognomonic, it may not be present at birth as seen in our case and can sometimes completely resolve with age.

Most of the reported mutations are nonsense mutations leading to a truncated LEKTI protein. Pathogenic variants in upstream of SPINK5 are associated with more severe phenotypes than those variants in 3' end. Splice site mutations could be associated with either severe or a mild phenotype depending on the proportion of normally spliced transcripts.[4] Both inter and intrafamilial variation in phenotype with the same mutation in the SPINK5 gene has been noted.

Neonates or infants with Netherton syndrome may be misdiagnosed as having congenital ichthyosiform erythroderma, atopic dermatitis, or psoriasis.

Neonatal presentation is very rare and requires multidisciplinary approach in intensive care units. Inspite of aggressive treatment, the prognosis is poor in severe cases. Remarkable clinical improvement has been noted with intravenous immunoglobulin treatment in few patients.[5] Kallikrein inhibitors, specifically KLK14, are new targets for drug development at present, but they have not been tested in patients with NS.


The authors would like to thank the patient and his family for their cooperation.

Declaration of consent

The authors certify that they have obtained all appropriate consent forms, duly signed by the parent(s) of the patient. In the form the parent(s) has/have given his/her/their consent for the images and other clinical information of their child to be reported in the journal. The parents understand that the names and initials of their child will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Hovnanian A. Netherton syndrome: Skin inflammation and allergy by loss of protease inhibition. Cell Tissue Res 2013;351:289-300.  Back to cited text no. 1
Chiticariu E, Hohl D. Netherton syndrome: Insights into pathogenesis and clinical implications. J Invest Dermatol 2020;140:1129-30.  Back to cited text no. 2
Miteva M, Tosti A. Dermatoscopy of hair shaft disorders. J Am Acad Dermatol 2013;68:473-81.  Back to cited text no. 3
Sarri CA, Roussaki-Schulze A, Vasilopoulos Y, Zafiriou E, Patsatsi A, Stamatis C, et al. Netherton syndrome: A genotype-phenotype review. Mol Diagn Ther 2017;21:137-52.  Back to cited text no. 4
Renner ED, Hartl D, Rylaarsdam S, Young ML, Monaco-Shawver L, Kleiner G, et al. Comèl-Netherton syndrome defined as primary immunodeficiency. J Allergy Clin Immunol 2009;124:536-43.  Back to cited text no. 5


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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