EGFR Mutation in Neonatal Nephrocutaneous Syndrome: Unveiling a Genetic Challenge

Abstract Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that exhibits tyrosine kinase signaling activity, playing a pivotal role in various cellular processes. Overexpression or overactivity of EGFR is significantly associated with inflammatory and malignant diseases, particularly lung cancer. Conversely, germline loss-of-function mutations in EGFR have been distinctly linked to a rare condition known as neonatal nephrocutaneous syndrome. We report a case of a preterm female neonate, born to consanguineous parents and from a pregnancy that was complicated by polyhydramnios. From birth, she displayed distinctive clinical features, including fragile skin and widespread erythema, sparse scalp hair, bilateral ankyloblepharon, thick eyebrows, and arachnodactyly. Subsequently, she developed progeroid features marked by skin desquamation, along with failure to thrive, diarrhea, and severe electrolyte and acid–base imbalances. Additional complications comprised anemia, generalized mucocutaneous candidiasis, external otitis, and recurrent septic episodes. Genetic analysis confirmed a homozygous EGFR mutation c.1283G > A p.(Gly428Asp). The infant's neurological status remained stable, albeit requiring pain management through oral morphine and gabapentin. Palliative care became imperative, given the dismal prognosis. The identified mutation is exceedingly rare, with only 24 reported cases known thus far. Each of these instances resulted in a complex multisystemic condition marked by a wide range of challenging symptoms and signs. This clinical journey highlights the intricate interplay among genetic mutations and complex medical conditions, and underscores the critical significance of multidisciplinary care.