Spectrum of ichthyoses in an Austrian ichthyosis cohort from 2004 to 2017

Abstract

Summary Background Ichthyoses are a heterogeneous disease group, which makes clinical classification challenging. An ichthyosis cohort at a center for genodermatoses is presented in detail. Patients and Methods Patients with clinically and/or genetically confirmed ichthyosis seen from 2004 to 2017 and listed in a database were included. Disease onset, phenotype, histology, comorbidities and family history were described in detail. In genetically tested patients, the prevalence of various ARCI genes, ARCI phenotypes and syndromic ichthyoses, as well as genotype‐phenotype correlation and year/method of genetic testing was assessed. Results Of all 198 patients who were included in the cohort, 151 were genetically tested. 81 had ichthyosis vulgaris, 43 X‐linked ichthyosis, 38 autosomal recessive congenital ichthyosis (ARCI), 9 keratinopathic ichthyosis (KPI) and one exfoliative ichthyosis. 26 individuals suffered from syndromic ichthyoses. A good genotype‐phenotype correlation was observed for common ichthyoses and KPI; the correlation was less good in syndromic ichthyoses. In 91 % of ARCI patients an accurate diagnosis was obtained by genetic testing. In only 33 % of syndromic ichthyoses was the definitive diagnosis suspected before genetic testing, which revealed a causative mutation in 86 % of cases. Conclusion This study describes the spectrum of ichthyoses in a center of expertise and shows that genetic testing should become a diagnostic standard for this disease group.

Quality of life and clinical characteristics of self‐improving congenital ichthyosis within the disease spectrum of autosomal‐recessive congenital ichthyosis

“…(11 British SICI patients) and recently from Seidl‐Philipp et al . (13 Austrian SICI patients) 4,6,21 . Our study adds the description of 18 SICI patients to this subject.…”

Novel Homozygous Mutations in the Genes TGM1, SULT2B1, SPINK5 and FLG in Four Families Underlying Congenital Ichthyosis

“…In the mammalian epidermis, the FLG protein plays a chief role in the aggregation of keratin intermediate filaments. Firstly, it is produced in the form of a precursor polyprotein molecule in the keratohyalin granules and then is proteolytically processed into the filaggrin molecules [ 40 , 41 ]. Further studies on knockout models have described that FLG protein is crucial for the development of the skin barrier and genetic alterations in the FLG lead to major predisposing factors for atopic disorders [ 42 ].…”

Mild Phenotype of Arthrogryposis, Renal Dysfunction, and Cholestasis Syndrome 1 Caused by a Novel VPS33B Variant

“…We then hypothesized that perhaps patients with missense variants in VPS33B gene might have an attenuated incomplete phenotype when compared with the ones with loss-of-function variants. On Supplementary Table S1, we compared our patient's phenotype with other patients reported in the literature with missense variants (Gissen et al, 2004;Cullinane et al, 2009;Tornieri et al, 2013;Gruber et al, 2017;Del Brio Castillo et al, 2019;Lee et al, 2019;Qiu et al, 2019;Seidl-Philipp et al, 2020).…”

“…The proband described by Lee et al (2019) had a missense variant in one allele and a splice site variant in the other allele, which could be influencing her phenotype (she carried p.Asp236Val and c.239+5G>A variants). Interestingly, three patients with the same missense p.(Gly131Glu) variant were described as having the phenotype of Keratoderma-ichthyosis-deafness (ARKID) syndrome, a rare multisystem disorder also caused by biallelic mutations in VPS33B (Gruber et al, 2017;Seidl-Philipp et al, 2020). It is important to note that at least six patients with incomplete phenotype have been reported with loss of functions variants, which shows that an incomplete phenotype is not always caused by missense variants-these patient's phenotypes were also summarized on the Supplementary Table S1 (Bull et al, 2006;Smith et al, 2012;Agawu et al, 2019;Agakidou et al, 2020;Duong et al, 2020b;a).…”