Fatal neonatal nephrocutaneous syndrome in 18 Roma children with EGFR deficiency

Abstract

Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with tyrosine-kinase signaling activity, involved in many cellular functions including cell growth and differentiation. Germ line loss-of-function mutations in EGFR lead to a severe neonatal skin disorder (Online Mendelian Inheritance in Man #131550). We report 18 premature Roma children from 16 families with birthweights ranging 440-1470 g and multisystem diseases due to the homozygous mutation c.1283G˃A (p.Gly428Asp) in EGFR. They presented with thin, translucent, fragile skin (14/ 15), skin desquamation (10/17), ichthyosis (9/17), recurrent skin infections and sepsis (9/12), nephromegaly (10/16) and congenital heart defects (7/17). Their prognosis was poor, and all died before the age of 6 months except one 13-year-old boy with a severe skin disorder, dentinogenesis imperfecta, Fanconi-like syndrome and secondary hyperaldosteronism. Management of ion and water imbalances and extremely demanding skin care may improve the unfavorable outcome of such patients.

The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions

“…Exons of the SSBP1 gene (NM_001256510) were analysed by Sanger sequencing, exome sequencing proceeded as described previously [ 15 ].…”

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

“…Dear Editor, 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.…”

“…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 1 reported 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.…”

“…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.…”

“…The clinical features of patients associated with EGFR deficiency were as follows: intrauterine growth restriction, thin, translucent and fragile skin (14/15 cases); skin desquamation (10/17 cases); ichthyosis (9/17 cases); recurrent skin infections and sepsis (9/12 cases); nephromegaly (10/16 cases); and congenital heart defects (7/17 cases). 1 Other possible comorbidities are erythroderma, dentinogenesis imperfecta, tubulopathy, necrotizing enterocolitis/intestinal perforation, testicular retention and hyperimmunoglobulin E, although their frequencies have not been reported. All but one of the children died within 2.5 years after birth.…”