Severe Hypernatremia as Presentation of Netherton Syndrome

Abstract

Netherton syndrome is a rare, multisystem, autosomal recessive genodermatosis characterized by a triad of manifestations: congenital ichthyosis, immune dysregulation, and scalp anomalies. We report the case of a 1-month-old male infant evaluated for failure to thrive and feeding difficulties. At birth, the infant was admitted to intensive care for severe hypernatremia (natremia 186 mg/dL). Upon entering the ward, the general conditions were poor. He presented with diffuse erythrodermia. A dermatological evaluation showed evidence of “invaginated trichuriasis,” a typical sign of Netherton syndrome. Netherton syndrome is caused by a genetic mutation causing loss of function of the SPINK5 gene it encodes for the LEKTI protein, normally expressed in epithelia. Loss of LEKTI induces severe skin barrier defect. The history of the disease is characterized by serious potential complications in the first months of life, such as the risk of hypernatremic dehydration induced by high skin permeability, recurrent and/or severe infections, and growth retardation.

Keywords

hypernatremia - genodermatosis - Trichorrhexis invaginata

Publication History

Article published online:
22 November 2023

• References

• 1 Mallory SB, Krafchik BR. What syndrome is this?. Pediatr Dermatol 1992; 2: 157-160
• 2 Roda Â, Mendonça-Sanches M, Travassos AR, Soares-de-Almeida L, Metze D. Infliximab therapy for Netherton syndrome: a case report. JAAD Case Rep 2017; 3 (06) 550-552
• 3 Shi ZR, Xu M, Tan GZ, Wang L, Guo Q, Tang ZQ. A case of Netherton syndrome with mutation in SPINK5 and FLG. Eur J Dermatol 2017; 27 (05) 536-537
• 4 Briot A, Lacroix M, Robin A, Steinhoff M, Deraison C, Hovnanian A. Par2 inactivation inhibits early production of TSLP, but not cutaneous inflammation, in Netherton syndrome adult mouse model. J Invest Dermatol 2010; 130 (12) 2736-2742
• 5 Comel M. [Ichthyosis linearis circumflexa]. Dermatologica 1949; 98 (03) 133-136
• 6 Netherton EW. A unique case of trichorrhexis nodosa; bamboo hairs. AMA Arch Derm 1958; 78 (04) 483-487
• 7 Orphanet: Comel Netherton Syndrome (2008). Accessed November 18, 2020 at: https:// www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=938& Disease_Disease_Search_diseaseType=ORPHA&Disease_Disease_Search_ diseaseGroup=634&Disease(s)/group%20of%20diseases=Comel-Nethertonsyndrome&title=Comel-Netherton-syndrome&search=Disease_Search_Simple
• 8 Bitoun E, Chavanas S, Irvine AD. et al. Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families. J Invest Dermatol 2002; 118 (02) 352-361
• 9 Bellon N, Hadj-Rabia S, Moulin F. et al. The challenging management of a series of 43 infants with Netherton syndrome: unexpected complications and novel mutations. Br J Dermatol 2021; 184 (03) 532-537
• 10 Jones SK, Thomason LM, Surbrugg SK, Weston WL. Neonatal hypernatraemia in two siblings with Netherton's syndrome. Br J Dermatol 1986; 114 (06) 741-743
• 11 Oddie SJ, Craven V, Deakin K, Westman J, Scally A. Severe neonatal hypernatraemia: a population based study. Arch Dis Child Fetal Neonatal Ed 2013; 98 (05) F384-F387
• 12 Panagoda R, De Cure N, McCuaig R, Kent AL. Neonatal hypernatraemic dehydration. J Paediatr Child Health 2015; 51 (06) 653-654
• 13 Lacroix M, Lacaze-Buzy L, Furio L. et al. Clinical expression and new SPINK5 splicing defects in Netherton syndrome: unmasking a frequent founder synonymous mutation and unconventional intronic mutations. J Invest Dermatol 2012; 132 (3, Pt 1): 575-582
• 14 Descargues P, Deraison C, Prost C. et al. Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsin-like hyperactivity in Netherton syndrome. J Invest Dermatol 2006; 126 (07) 1622-1632
• 15 Chavanas S, Bodemer C, Rochat A. et al. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet 2000; 25 (02) 141-142
• 16 Guerra L, Fortugno P, Sinistro A. et al. Betapapillomavirus in multiple non-melanoma skin cancers of Netherton syndrome: case report and published work review. J Dermatol 2015; 42 (08) 786-794
• 17 National Center for Biotechnology Information. ClinVar [VCV000459573.6]. Accessed December 19, 2021 at: https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000459573.6
• 18 Sarri CA, Roussaki-Schulze A, Vasilopoulos Y. et al. Netherton syndrome: a genotype-phenotype review. Mol Diagn Ther 2017; 21 (02) 137-152
• 19 Tartaglia-Polcini A, Bonnart C, Micheloni A. et al. SPINK5, the defective gene in Netherton syndrome, encodes multiple LEKTI isoforms derived from alternative pre-mRNA processing. J Invest Dermatol 2006; 126 (02) 315-324
• 20 Herz-Ruelas ME, Chavez-Alvarez S, Garza-Chapa JI, Ocampo-Candiani J, Cab-Morales VA, Kubelis-López DE. Netherton syndrome: case report and review of the literature. Skin Appendage Disord 2021; 7 (05) 346-350
• 21 Mazereeuw-Hautier J, Vahlquist A, Traupe H. et al. Management of congenital ichthyoses: European guidelines of care, part one. Br J Dermatol 2019; 180 (02) 272-281
• 22 Zingkou E, Pampalakis G, Sotiropoulou G. Cathelicidin represents a new target for manipulation of skin inflammation in Netherton syndrome. Biochim Biophys Acta Mol Basis Dis 2020; 1866 (10) 165831