CYP4F22-Related Autosomal Recessive Congenital Ichthyosis Q80.-

Autosomal recessive congenital ichthyosis type V (-ARCI5) belongs to the heterogeneous group of genetic dermatoses characterized by keratinization disorders, generalized scaling and extreme dryness of the skin. The ARCI group of ichthyoses refers to diseases that were previously referred to as ichthyosis congenita.

Type V (ARCI 5) is characterized by mutations in the fatty acid alpha-hydroxylase gene CYP4F22. Among the ARC I-associated genes, CYP4F22 encodes proteins and enzymes involved in the biosynthesis of ceramide. Ceramide is responsible for the integrity of the skin permeability barrier as well as for the formation of the intracellular lipid bilayer. The CYP4F22 phenotype of ARCI depends on the type of gene mutation. Most patients are born with marked erythroderma without collodion membrane, with hyperlinearity of the palms and soles and extensive scaling of the scalp (Dumenigo A et al. 2022) .

The CYP4F22 gene is located on chromosome 19p13.12 and encodes a P450 cytochrome homolog of leukotriene B4-ω-hydroxylase. CYP4F22 is the fatty acid ω-hydroxylase gene required for the production of acylceramide, an important lipid for the integrity of the skin permeability barrier. This gene is also involved in the 12(R)-lipoxygenase signaling pathway, which is used for arachidonic acid metabolism and eicosanoid synthesis (Dumenigo A et al. 2022).

Variants in other genes (e.g. homozygous CYP4F22 mutation and monoallelic FLG variant) lead to overlapping clinical manifestations of autosomal recessive congenital ichthyosis and mild ichthyosis vulgaris. Mutations that lead to a loss of function of fillagrin predispose to atopic dermatitis and can also act as modifiers in other forms of ichthyosis (Casetti F et al. (2024).

Congenital ichthyosis associated with CYP4F22 can occur at birth with or without a collodion membrane, depending on the type of gene mutation. Patients with a homozygous CYP4F22 missense mutation are not born with a collodion membrane, whereas patients with one or two mutations in the substrate binding region can be born with a collodion membrane (Dumenigo A et al. 2022). Most patients with a CYP4F22 mutation are born with marked erythroderma without collodion membrane, hyperlinearity of the palms and soles and scaling of the scalp and develop a milder LI or CIE phenotype later in life.

S. under ichthyosis

Remarkable therapeutic successes with dupilumab and ustekinumab (Casetti F et al. 2024).

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