ILVEN is increasingly understood as a mosaic inflammatory disorder caused by post-zygotic (somatic) mutations in keratinocyte-related genes. Recent genomic reports have implicated mutations in genes including GJA1 (connexin 43) and CARD14 among others; however, the genetic landscape is heterogeneous and research is evolving. The molecular findings help explain phenotypic overlap with other inflammatory disorders. Most cases are sporadic, but a familial cases do exis, with the condition occurring in a mother and her daughter. Another case was described in a father and son. It also has been proposed that activation of an
autosomal dominant lethal mutation that survives by mosaicism may be the cause of the lesions. The mutated cells may survive in the due to proximity of normal cells. Another theory is that
retrotransposable elements may be the cause of all skin conditions along the Lines of Blashko. Some dogs have a coat variation based upon a similar mechanism.
Associated Mutations •
ABCA12 mutation causes a lamellar granule dysfunction and lipid barrier defect which in turn causes a linear
ichthyosiform ILVEN-like plaques •
CARD14 mutation activates the
NF-κB and
IL-12/
IL-23/
IL-17 pathway that causes a psoriaform ILVEN •
GJA1 (also known as Connexin 43) mutation causes a type of
gap junction dysfunction also known to cause
erythrokeratodermia variabilis et progressiva •
HRAS the mutation that involved in ILVEN is a
RAS-
MAPK pathway hyperactivation (
RASopathy-related). •
KRT10 mutation causes
keratinocyte differentiation abnormality causes systematized ILVEN with hyperkeratosis •
NSDHL mutation disrupts
cholesterol biosynthesis in a manner similar to
CHILD syndrome, but in Blaschko-linear plaques •
PMVK mutation causes impaired
mevalonate pathway with second-hit mosaicism causes ILVEN-like linear porokeratosis with cornoid lamellae ==Histopathology==