Overview of genetic causes of patients with congenital ichthyosis: single centre experience

Background. Congenital ichthyosis is a heterogeneous group of keratinisation disorders characterised primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, but patients can have systemic symptoms. There are variable inheritance patterns and several genetic causes. Aim. The aim of the current study was to analyse genetically tested patients, and their genetic causes. Methods. A total of 15 patients having symptoms of ichthyosis were consulted by dermatologist and clinical geneticist in the Hospital of Lithuanian University of Health Sciences, Kauno Klinikos, in the period from 2020 to 2024. Demographic data, genotypes, phenotypes from electronical medical records were analysed. Genetic testing was performed using whole exome sequencing with virtual genetic skin disorders panel. Large gene deletions confirmed with molecular karyotyping. Results. Genetic diagnosis of ichthyosis was confirmed to all 15 patients, 8 (53.33%) male patients. Variants in STS, ALOX12B, ABCA12, KRT10, KRT2, ZMPSTE24 genes were detected. Seven (43.75%) patients had a variant in STS gene, inherited as X linked recessive manner. Six patients had hemizygous deletion Xp22.31, and one patient had a frame shift variant. Clinically dry skin with mild scaling was noted. Two patients also had mild erythema. Two(18.75%) patients had a variant in ALOX12B gene. Two patients had compound heterozygous variant. One of them had hypopigmentation and hyperkeratosis, and another had erythroderma, painful palmoplantar keratoderma with fissures. The 3rd patient with two potentially pathogenic variants was born as a collodion baby. One patient had a compound heterozygous variant in ABCA12 gene. The phenotype was found of scaling skin with moderate dandruffs, poor nail growth, pruritus. One patient had a heterozygous variant in KRT10 gene. It lead to autosomal dominant congenital bullous ichthyosiform erythroderma which presented with hyperkeratotic lichenification, erosions with yellow crusts on skin. One patient had a heterozygous variant in KRT2 gene that caused superficial epidermolytic ichthyosis. Hypertrichosis, hyperkeratotic brown-yellow like skin was noted. One (12.50%) patient had a homozygous variant in ZMPSTE24 gene. It caused restrictive dermopathy (ORPHA:1662). Limb contractures, pulmonary hypoplasia and skin cracks were noted. Both patients died during the first weeks of life. Conclusion. Causes of congenital ichthyoses was genetically heterogenous, predominantly with STS gene deletion. Hence, genetic testing is crucial for prognosis and classification, as ichthyosis manifests differently due to affected gene.