This methodology successfully achieved molecular diagnosis in all four analyzed ARCI patients by identifying seven pathogenic variants in ALOX12B and CYP4F22. The multi-gene analysis allowed the identification of additional heterozygous variants in different ARCI genes, i.e., ABCA12 and STUB2B1, which could be negative modifiers of the CIE phenotype associated with ALOX12B deficiency, in our patients. This evidence concerns the gene ALOX12B and autosomal recessive congenital ichthyosis.