Systemic inflammatory diseases due to germ line EGFR mutations, with features suggestive of autoinflammatory keratinization diseases

Abstract

We read with great interest the mutation report of fatal neonatal nephrocutaneous syndrome in 18 Roma children by Mazurova et al. 1 Systemic inflammatory diseases caused by a germ line mutation in EGFR encoding epidermal growth factor receptor (EGFR) were first reported in 2014, as neonatal inflammatory skin and bowel disease (Online Mendelian Inheritance in Man #616069). 2 Later, Ganetzky et al. 3 described a lethal syndrome of epithelial dysfunction with progeroid features caused by the identical EGFR mutation. Mazurova et al. 1reported premature children with multisystem diseases, including one surviving 13-year-old boy with severe skin symptoms including ichthyosiform skin desquamation, as well as dentinogenesis imperfecta, Fanconi-like syndrome and secondary hyperaldosteronism. These findings extend the spectrum of EGFR mutations and provide further evidence for the genetic basis of disorders due to EGFR deficiency. 1 Inspired by their report, we propose that systemic inflammatory diseases caused by germ line EGFR mutations be categorized as autoinflammatory keratinization diseases (AiKD). 4 Figure 1. Suggested inflammatory pathways and processes induced by germ line EGFR mutations in the present autoinflammatory keratinization disease. CXCL1, C-X-C motif chemokine 1; EGFR, epidermal growth factor receptor; IL, interleukin; JNK1, c-Jun Nterminal kinase 1; NF-jB, nuclear factor-jB; PLA2, phospholipase A2.