Ichthyosis with Confetti (IWC) is an autosomal dominant disorder of keratinization that is exceedingly rare, with approximately 40 cases reported. Although patients generally demonstrate ichthyosiform erythroderma at birth, the disorder is defined by the hundreds of confetti-like white spots that appear in childhood and grow in size and number over time (Choate and Milstone, 2015; Guerra et al., 2015). The histopathology of the red skin surrounding the macules shows perinuclear vacuolization, loss of the granular layer, and parakeratotic hyperkeratosis, whereas the white, revertant macules are histologically normal (Choate and Milstone, 2015).

The mutations identified in IWC to date arise de novo and cause frameshift deletions affecting the carboxyl tail of keratin 10 (K10) or keratin 1 (K1), causing Type I IWC (IWCI) and Type II IWC (IWC-II), respectively (Choate et al., 2010; Choate et al., 2015). Prior investigation of 7 independent IWC-I probands identified distinct mutations causing entry into the same aberrant reading frame invariably replacing the endogenous glycine-rich tail of K10 with a polyarginine sequence (Choate et al., 2010; Guerra et al., 2015). In IWC-II, the K1 glycine tail is maintained, but the final 22 residues of the end domain are replaced with a novel 30 amino acid, non-repeating sequence (Choate et al., 2015).