Epidermal growth factor receptor deficiency: Expanding the phenotype beyond infancy

Area of Science:

• Genetics and Molecular Biology
• Dermatology
• Immunology

Background:

• Transmembrane tyrosine kinase receptors, like the epidermal growth factor receptor (EGFR), are crucial for cell signaling.
• Dysregulation of EGFR is implicated in various cancers.
• EGFR deficiency is a rare genetic disorder causing multisystemic issues.

Purpose of the Study:

• To present the clinical phenotype and long-term outcomes of the longest-surviving patient with EGFR deficiency.
• To deepen the understanding of the natural history of this rare genetic disorder.
• To investigate the genetic basis of EGFR deficiency.

Main Methods:

• Whole-exome sequencing to identify genetic variants.
• Clinical phenotyping of the patient, including dermatological and immunological assessments.
• Review of existing literature on EGFR deficiency.

Main Results:

• A homozygous loss-of-function variant in EGFR (c.1283G>A; p.[G428D]) was identified.
• The patient presented with severe skin issues (friable skin, ichthyotic rash, alopecia) and recurrent infections.
• Despite early mortality in other cases, this patient stabilized with supportive care, showing dermatological improvement and reduced infections by age 8.

Conclusions:

• EGFR deficiency is a severe multisystemic disorder with significant dermatological and immunological manifestations.
• The longest-surviving patient demonstrates that stabilization is possible with supportive interventions.
• This case expands the understanding of EGFR deficiency's natural history and potential therapeutic avenues.