Fatal neonatal nephrocutaneous syndrome in 18 Roma children with EGFR deficiency

J Dermatol. 2020 Jun;47(6):663-668. doi: 10.1111/1346-8138.15317. Epub 2020 Apr 6.

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.

Keywords: epidermal growth factor receptor; ichthyosis; neonate; nephrocutaneous syndrome; progeria.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Czech Republic / epidemiology
  • Dentinogenesis Imperfecta / diagnosis
  • Dentinogenesis Imperfecta / genetics
  • Dentinogenesis Imperfecta / mortality*
  • ErbB Receptors / deficiency
  • ErbB Receptors / genetics
  • Exome Sequencing
  • Heart Defects, Congenital / diagnosis
  • Heart Defects, Congenital / genetics
  • Heart Defects, Congenital / mortality*
  • Homozygote
  • Humans
  • Ichthyosis / diagnosis
  • Ichthyosis / genetics
  • Ichthyosis / mortality*
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Infant, Very Low Birth Weight
  • Kidney Diseases / congenital
  • Kidney Diseases / diagnosis
  • Kidney Diseases / genetics
  • Kidney Diseases / mortality*
  • Loss of Function Mutation
  • Roma / genetics*
  • Severity of Illness Index
  • Slovakia / epidemiology
  • Syndrome

Substances

  • EGFR protein, human
  • ErbB Receptors