PA11 A rare case of a severe papulopustular dermatosis secondary to a germline EGFR mutation

Abstract

A Slovakian female neonate presented at 1 month of age with a dry, scaly scalp and erythematous papules affecting the scalp and face. She was born preterm at 35 weeks’ gestation by emergency caesarean section, following a pregnancy complicated by intra­uterine growth restriction, marked polyhydramnios requiring amniocentesis and cervical cerclage. Renal tubulopathy was identified at birth, with negative genetic testing for Bartter syndrome. Clinical features included an extensive papulopustular eruption, minimal scalp hair growth and recurrent methicillin-resistant Staphylococcus aureus cutaneous infections. Scalp biopsy demonstrated a neutrophilic follicular infiltrate. Whole-exome sequencing confirmed a homozygous pathogenic missense loss-of-function mutation in the epidermal growth factor receptor gene (EGFR), c.1283G>A (p.Gly428Asp). She was later diagnosed with bicoronal craniosynostosis, requiring corrective surgery at 9 months of age. Additional complications included unsafe swallow necessitating percutaneous endoscopic gastrostomy–­jejunostomy placement and global developmental delay. No congenital cardiac abnormalities were identified. There was no prior family history, including in an older sibling born preterm at 27 weeks’ gestation. The parents were nonconsanguineous and had two prior miscarriages and one stillbirth at 22 weeks’ gestation due to preterm labour. EGFR encodes a transmembrane tyrosine kinase essential for epithelial growth and differentiation. Germline loss-of-function EGFR mutations are exceptionally rare, with fewer than 25 cases reported worldwide since 2014. Most affected individuals share the same homozygous mutation and are of Slovakian Roma ancestry, suggesting a founder effect. Reported features include severe neonatal skin fragility, ichthyosis, papulopustular eruptions, sparse hair, recurrent infections and multisystem involvement, with antenatal polyhydramnios, growth restriction and craniofacial abnormalities being common. Mortality is high, with survival beyond infancy reported in only one prior case. Our patient, now 4 years old, is receiving ongoing multidisciplinary care with paediatric hospice support. This case highlights the characteristic phenotype of germline EGFR loss of function and the importance of genetic diagnosis in severe neonatal dermatoses.