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.

Department of Medical Genetics Masaryk Hospital in Usti nad Labem Regional Health Corporation Usti nad Labem Czech Republic

Department of Neonatology Pediatric University Hospital Kosice Slovak Republic

Department of Pediatrics and Adolescent Medicine General University Hospital 1st Medical Faculty Charles University Prague Czech Republic

Department of Pediatrics Thomayer Hospital 1st Medical Faculty Charles University Prague Czech Republic

Institute of Biology and Medical Genetics General University Hospital 1st Medical Faculty Charles University Prague Czech Republic

Laboratory of Clinical Genetics Medirex Inc Kosice Slovak Republic

Laboratory of Genetics Medirex Inc Bratislava Slovak Republic

Newborn Screening Center Slovak Republic Children's University Hospital Banska Bystrica Slovak Republic

See more in PubMed

Robichaux JP, Elamin YY, Tan Z et al. Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Nat Med 2018; 24: 638-646.

Eck MJ, Yun CH. Structural and mechanistic underpinnings of the differential drug sensitivity of EGFR mutations in non-small cell lung cancer. Biochim Biophys Acta 2010; 1804: 559-566.

Campbell P, Morton PE, Takeichi T et al. Epithelial inflammation resulting from an inherited loss-of-function mutation in EGFR. J Invest Dermatol 2014; 134: 2570-2578.

Ganetzky R, Finn E, Bagchi A et al. EGFR mutations cause a lethal syndrome of epithelial dysfunction with progeroid features. Mol Genet Genomic Med 2015; 3: 452-458.

Hayashi S, Yokoi T, Hatano C et al. Biallelic mutations of EGFR in a compound heterozygous state cause ectodermal dysplasia with severe skin defects and gastrointestinal dysfunction. Hum Genome Var 2018; 5: 11.

Ehmann LM, Ruzicka T, Wollenberg T. Cutaneous side-effect of EGFR inhibitors and their management. Skin Therapy Lett 2011; 16: 1-3.

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