This is the most severe type of autosomal congenital recessive ichthyosis and the most severe keratinization disorder known. At birth the children are encased in a very thick armor like keratotic cast. Thick yellow keratotic plates can be noted that crack resulting in deep, irregularly branched fissures. In its most severe form even today many children still die in the first weeks of life.

There are also somewhat milder forms resembling collodion baby. Similar to the collodion baby, children suffering from harlequin ichthyosis should be admitted right after birth to a neonatal intensive care unit and require an interdisciplinary therapy.

The disease is due to very peculiar mutations in the gene ABCA12. These mutations even affect the prognosis for survival. If so called homozygous mutations which are identical in both parents are present the prognosis is less good compared to the prognosis if both parents have different (compound heterozygous) mutations in the ABCA12 gene. Homozygous mutations are often found if the parents are related to each other (consanguinity). Nowadays, harlequin ichthyosis is considered to be a distinct form of ARCI (see next chapter).