Longest surviving patient with a homozygous splice-altering EGFR pathogenic variant presenting with skin autoinflammation and a Bartter-like salt-losing tubulopathy.
Leila Youssefian, Sajjad Biglari, Fatemeh Vahidnezhad et al.
✦ AI-curated · Sources linked
Case in brief
An adolescent patient with a Bartter-like phenotype presented with progressive nephrocalcinosis, hypercalciuria, and skin autoinflammation. Genetic analysis revealed a homozygous splice-altering variant in the EGFR gene, leading to aberrant splicing and reduced protein levels. This variant was associated with the patient's symptoms and allowed for survival into adolescence, contrasting with previously reported severe outcomes linked to EGFR variants.
What made this case unusual
The case highlights a homozygous splice-altering EGFR variant that resulted in a hypomorphic effect, allowing for prolonged survival despite severe clinical manifestations typically associated with EGFR mutations.
Diagnostic / clinical pearl
Clinicians should consider the possibility of hypomorphic variants in EGFR when evaluating patients with atypical presentations of Bartter syndrome and associated autoinflammatory conditions.
Why it matters
This case expands the understanding of EGFR-related disorders, illustrating that certain splice-altering variants can lead to a milder phenotype and prolonged survival, which may influence genetic counseling and management strategies.