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Congenital ichthyosis

Congenital ichthyoses are present since birth and as a rule show a more severe manifestation than the so-called vulgar or noncongenital ichthyosis. The most important and most frequent types of congenital lamellar ichthyosis are the

Autosomal recessive lamellar ichthyosis / autosomal recessive nonbullous congenital ichthyosis.

They are much less frequent than ichthyosis vulgaris. The prevalence has been estimated to be 1 in 100.000. As stated above in Germany the terms “lamellar ichthyosis” or “nonbullous congenital ichthyosis" are used as synonyms. The autosomal recessive lamellar ichthyosis do not form a uniform entity, but a group of different genetically caused diseases. As it has already been discussed above several different loci are known which result in lamellar ichthyosis. The clinical phenotype that is the severity of lamellar ichthyosis can be very variable.

At birth a collodion membrane is frequently present. The skin can be completely red in the sense of a red neonate (the medical term would be erythroderma) whereas other affected show no marked erythema of the skin. The size and colour of the scales are also highly variable. Many have a fine light brown scaling, while in others a much thicker platelike and often dark scaling can be found. The scales are composed of thin layers that lie above each other like different lamella, therefore the term “lamellar ichthyosis”. Due to the extreme dryness of the skin eyelids can become everted and a so-called ectropion can develop. In almost all cases palms and soles show either accentuated creases or some degree of diffuse palmoplantar keratosis. The big body folds such as the antecubital fold, the popliteal folds, the groins, the face and the scalp are usually involved.

The much thickened horny layer results in plugging of the ducts of the sweat glands which means that the capability to perspire is in almost all patients markedly diminished. Many doctors are not aware of this significant problem. In summer or when the temperature is high in the general surroundings this can result in an increase of the body temperature which means fever. Therefore it is important to observe these infants in hot summer months and to provide adequate cooling perhaps even by wet dressings. The children usually learn rather early that heat and also strong sun exposure is not good for them. This should also be considered when thinking of vacations.

Quite a few patients with congenital or lamellar ichthyosis also show defects of the finger and foot nails which can be curved and often have a disturbed growth. Disturbances of the hair are not so common. However, these can occur if there are platelike keratinizations on the scalp and may result in scarring alopecia.

As discussed above mutations in the gene encoding the enzyme transglutaminase have been identified. This gene resides on the long arm of chromosome 14 in the position 11. Transglutaminase-1 is responsible for formation of the cornified cell envelope. As already discussed above a further locus has been found on the long arm of chromosome 2 in the section 33-35 having a function as a lipid transport gene. As also mentioned above two further genetic loci have been identified on the short arm of chromosome 17 encoding genes for epidermal lipoxygenases. A further gene encoding "ichthyin" probably has a functional role in the same "hepoxilin pathway". Further loci on chromosome 9q34 and also on chromosome 19 are known, but the responsible proteins encoded by these genes have not yet been identified. It is not possible to predict from the clinical phenotype the underlying gene and in particular there is no correlation between the severity of ichthyosis in an individual patient and the underlying gene mutation. In particular in those patients having a deficiency of transglutaminase-1 the phenotype can be very broad and range from severe lamellar ichthyosis to that of self healing collodion baby. In the experience of our network patients with lipoxygenase mutations tend to have a rather mild phenotype in most instances.

Transglutaminase-1 activity in the skin a) normal activity with strong presence of the enzyme in the stratum granulosum, b) lacking activity in a patient having transglutaminase-1 deficiency as the cause of his lamellar ichthyosis.
Brigitte.Willis@ukmuenster.de, 16.06.2009