Recessive x-linked ichthyosis (RXLI)

This type of ichthyosis is the second most frequent type having a prevalence in the population of about 1 : 4000. As it affects almost exclusively males, prevalence in the male population is about 1 : 2000. The disease is x-linked and females are genetic conductors who are free of the disease, or occasionally express minimal signs like minimal scaling on the lower legs.

This disease mostly starts in infancy, but a few patients exhibit right after birth a fine scaling that vanishes after a few weeks. The disease then comes back mostly affecting initially the lower legs with a whitish scaling, resembling ichthyosis vulgaris. With increasing age the scaling turns darker and becomes more adherent and rhombic. The big body folds are usually spared just like in ichthyosis vulgaris. Palms and soles show now increased creases (hyperlinearity). (If they do this may indicate a concomitant filaggrin mutation). A further feature may be changes affecting the cornea of the eye which mostly has no clinical consequences. In our experience one in five affected boys suffered from cryptorchidism or a mild form of testicular maldescent. Moreover, there is a proneness to autism and attention deficit hyperactivity syndrome in 20 to 40% of the patients.

The gene involved concerns the enzyme steroid sulfatase. This enzyme is needed to desulfate cholesterol sulfate among else. A deficiency results in an accumulation of cholesterol sulfate in the lipid lamellae of the stratum corneum. Biochemical screening for the enzyme activity or for accumulated metabolic allow a fast recognition of the disease by a blood test. Genetic mutation testing (screening) is tedious as many mutations are due to gene deletions.

The disease occurs almost exclusively in the male gender as males have only a single copy of the x-chromosome. In contrast to women, males lack the second x-chromosome which allows women to compensate a genetic defect on the other x-chromosome. This means that as a general rule women do not develop the disease, but can transmit a mutant x-chromosome to their sons who will then develop ichthyosis. In extremely rare cases women can develop the disease if both their x-chromosomes happen to be mutated in the STS gene locus. For entire Germany having 82 million inhabitants we expect about five affected women. This is in striking contrast to round about ten thousand affected males.