P05.023.C When the phenotype is more severe than expected: coexistence of X-linked and dominant ichthyosis in an African patient. Hybrid Poster

Background/Objectives
The most common types of ichthyosis are autosomal dominant or ichthyosis vulgaris and X-linked recessive ichthyosis. Clinical forms of these diseases are quite indistinguishable. Ichthyosis vulgaris is caused by heterozygous mutations in the FLG gene encoding filaggrin. For the X-linked recessive form, mainly males are affected and the majority of the cases are caused by complete deletion of the steroid sulfatase gene (STS) on chromosome Xp22.3. Other cases result from partial deletion or point mutations of the STS gene. Co-segregation of both ichthyosis types has been described previously in several populations, but to the best of our knowledge not in African population. Filaggrin defects seem to synergize with deficient activity of steroid-sulfatase causing exacerbation of the clinical features.
Methods
We present an African patient with a very severe phenotype of ichthyosis. Meticulous phenotyping with molecular confirmation of both X-linked recessive and autosomal form of ichthyosis was obtained.
Results
Accurate clinical examination and skin biopsy led to clinical diagnosis of severe ichthyosis. Subsequently gene panel analysis by exome seqencing confirmed a hemizygote intragentic deletion of STS in co-existence with a heterozyguous likely pathogenic variant in FLG.
Conclusion
Ichthyosis vulgaris and X-linked recessive ichthyosis are well known and clinically similar, with variable severity. We describe the first African patient with confirmed coexistence of both ichthyosis forms, causing severe exacerbation of the clinical features, with impotant mental health implications.
References
Alaverdian DA et al. Metab Pers Ther. 2019
Wang X et al. Med Genet. 2018
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