Ultrastructural features resembling those of harlequin ichthyosis in patients with severe congenital ichthyosiform erythroderma

Congenital ichthyoses are a group of heterogeneous disorders of cornification. Autosomal recessive congenital ichthyosis (ARCI) can be clinically subdivided into congenital ichthyosiform erythroderma and lamellar ichthyosis. Ultrastructurally, ARCI is classified into four groups: ichthyosis congenita (IC) types I–IV. The genetic background of the ARCI disorders is heterogeneous, but only one disease gene, transglutaminase 1, has been detected so far. We describe six patients with severe congenital ichthyosis from six different Scandinavian families. They could not be classified ultrastructurally into the four IC groups because of atypical findings of electron microscopy. These included abnormal lamellar bodies, alterations in keratohyalin, remnant organelles and lipid inclusions in the upper epidermal cells, which resembled the ultrastructural findings of harlequin ichthyosis (HI), although the HI phenotype was not present at birth. Some clinical features, such as thick scales, erythroderma, alopecia and ectropion were common to all patients. Ichthyosis was usually accentuated in the scalp and four patients had clumped fingers and toes. None of the patients carried the transglutaminase 1 mutation. We conclude that ultrastructural findings resembling those detected in previous HI cases (type 1 and 2) can also be found in patients who do not have classic clinical features of that rare ichthyosis. This may be due to lack of specificity of ultrastructural markers for HI or to its clinical heterogeneity.