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Skin Therapy Letter Jan 2020The ichthyoses, also termed the disorders of keratinization, are a heterogenous group of skin diseases in which a distinctive horny layer arises secondary to excessive... (Review)
Review
The ichthyoses, also termed the disorders of keratinization, are a heterogenous group of skin diseases in which a distinctive horny layer arises secondary to excessive transepidermal water loss. Although occasionally acquired, the majority of ichthyoses are inherited and can be pinpointed to characteristic genetic mutations. Management depends on disease severity and includes topical agents and lifestyle modifications with or without oral retinoids. Genetic counseling is also an important consideration. This review aims to highlight advances in our understanding of disease pathogenesis as well as the holistic approach necessary to adequately manage ichthyosis patients.
Topics: Dermatologic Agents; Genetic Counseling; Humans; Ichthyosis; Life Style; Mutation; Retinoids; Severity of Illness Index
PubMed: 32023022
DOI: No ID Found -
Indian Journal of Dermatology,... 2022
Review
Topics: Acantholysis; Diagnosis, Differential; Humans; Ichthyosis; Skin; Skin Diseases
PubMed: 34245536
DOI: 10.25259/IJDVL_1028_20 -
BMJ Case Reports Feb 2021
Topics: Humans; Hyperkeratosis, Epidermolytic; Skin
PubMed: 33602779
DOI: 10.1136/bcr-2020-240424 -
Human Genetics Oct 2023DBR1 encodes the only known human lariat debranching enzyme and its deficiency has been found to cause an autosomal recessive inborn error of immunity characterized by...
DBR1 encodes the only known human lariat debranching enzyme and its deficiency has been found to cause an autosomal recessive inborn error of immunity characterized by pediatric brainstem viral-induced encephalitis (MIM 619441). We describe a distinct allelic disorder caused by a founder recessive DBR1 variant in four families (DBR1(NM_016216.4):c.200A > G (p.Tyr67Cys)). Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life. Patient-derived fibroblasts displayed the characteristic accumulation of intron lariats in their RNA as revealed by targeted and untargeted analysis, in addition to a marked reduction of DBR1 on immunoblot analysis. We propose a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility and highlight the apparent lack of correlation with the degree of DBR1 deficiency.
Topics: Child; Humans; Alleles; Causality; Encephalitis; Fibroblasts; Ichthyosis
PubMed: 37656279
DOI: 10.1007/s00439-023-02597-3 -
The British Journal of Dermatology Jul 2023
Topics: Humans; Toll-Like Receptor 2; Ichthyosis; Ichthyosis, Lamellar; Phenotype; Health Services
PubMed: 37418647
DOI: 10.1093/bjd/ljad177 -
Molecular Genetics and Metabolism 2021Cutaneous signs and symptoms may facilitate the diagnosis or can help in identifying complications or side effects of overtreatment of inherited metabolic diseases. The... (Review)
Review
Cutaneous signs and symptoms may facilitate the diagnosis or can help in identifying complications or side effects of overtreatment of inherited metabolic diseases. The principal manifestations can be grouped into vascular lesions, ichthyosis, papular and nodular skin lesions, abnormal pigmentation, photosensitivity, skin laxity, hair shaft involvement, and nail abnormalities. We have summarized associations of these cutaneous signs and symptoms in 252 inherited metabolic diseases. This represents the sixth of a series of articles attempting to create and maintain a comprehensive list of clinical and metabolic differential diagnoses according to system involvement.
Topics: Diagnosis, Differential; Humans; Ichthyosis; Metabolic Diseases; Metabolism, Inborn Errors; Overtreatment; Skin; Skin Diseases
PubMed: 34304991
DOI: 10.1016/j.ymgme.2021.07.005 -
MMW Fortschritte Der Medizin Nov 2023
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Journal of Medical Genetics Jul 2023Genetic deletions at Xp22.31 are associated with the skin condition X linked ichthyosis (XLI), and with a substantially increased risk of atrial fibrillation/flutter...
BACKGROUND
Genetic deletions at Xp22.31 are associated with the skin condition X linked ichthyosis (XLI), and with a substantially increased risk of atrial fibrillation/flutter (AF), in males. AF is associated with elevated thrombosis, heart failure, stroke and dementia risk.
METHODS
Through: (a) examining deletion carriers with a diagnosis of AF in UK Biobank, (b) undertaking an online survey regarding abnormal heart rhythms (AHRs) in men/boys with XLI and female carriers of XLI-associated deletions and (c) screening for association between common genetic variants within Xp22.31 and idiopathic AF-related conditions in UK Biobank, we have investigated how AHRs manifest in deletion carriers, and have identified associated risk factors/comorbidities and candidate gene(s). Finally, we examined attitudes towards heart screening in deletion carriers.
RESULTS
We show that AHRs may affect up to 35% of deletion carriers (compared with <20% of age-matched non-carriers), show no consistent pattern of onset but may be precipitated by stress, and typically resolve quickly and respond well to intervention. Gastrointestinal (GI) conditions and asthma/anaemia were the most strongly associated comorbidities in male and female deletion carriers with AHR, respectively. Genetic analysis indicated significant enrichment of common AF risk variants around (7 065 298-7 272 682 bp in GRCh37/hg19 genome build) in males, and of common GI disorder and asthma/anaemia risk variants around (7 866 804-7 895 780 bp) in males and females, respectively. Deletion carriers were overwhelmingly in favour of cardiac screening implementation.
CONCLUSION
Our data suggest AHRs are frequently associated with Xp22.31 deletion, and highlight subgroups of deletion carriers that may be prioritised for screening. Examining cardiac function further in deletion carriers, and in model systems lacking steroid sulfatase, may clarify AF pathophysiology.
Topics: Humans; Male; Female; Ichthyosis, X-Linked; Heterozygote; Surveys and Questionnaires; Heart Defects, Congenital; Heart
PubMed: 36379544
DOI: 10.1136/jmg-2022-108862 -
Acta Dermato-venereologica Mar 2020Inherited ichthyoses are classified as Mendelian disorders of cornification (MEDOC), which are defined on the basis of clinical and genetic features and are mainly... (Review)
Review
Inherited ichthyoses are classified as Mendelian disorders of cornification (MEDOC), which are defined on the basis of clinical and genetic features and are mainly divided into non-syndromic and syndromic ichthyoses. Numerous genes, which encode for corresponding proteins, are involved in the normal differentiation of keratinocytes (cornification) and participate in the formation of a functional epidermal barrier. To date, mutations in more than 50 genes are known to result in various types of ichthyoses. Thanks to modern genetic diagnostic methods based on targeted next generation sequencing (NGS), approximately 80-90% of cases can be resolved at present. Further sequencing methods covering the whole exome (WES) or whole genome (WGS) will obviously elucidate another portion of the remaining unknown ichthyoses in the future.
Topics: Alopecia; Chondrodysplasia Punctata; Congenital Disorders of Glycosylation; Humans; Ichthyosis; Ichthyosis Vulgaris; Ichthyosis, X-Linked; Mutation; Photophobia; Skin Diseases, Genetic; Skin Physiological Phenomena
PubMed: 32147747
DOI: 10.2340/00015555-3432 -
The British Journal of Dermatology Oct 2022The ichthyoses are rare genetic keratinizing disorders that share the characteristics of an impaired epidermal barrier and increased risk of microbial infections....
BACKGROUND
The ichthyoses are rare genetic keratinizing disorders that share the characteristics of an impaired epidermal barrier and increased risk of microbial infections. Although ichthyotic diseases share a T helper (Th) 17 cell immune signature, including increased expression of antimicrobial peptides, the skin microbiota of ichthyoses is virtually unexplored.
OBJECTIVES
To analyse the metagenome profile of skin microbiome for major congenital ichthyosis subtypes.
METHODS
Body site-matched skin surface samples were collected from the scalp, upper arm and upper buttocks of 16 healthy control participants and 22 adult patients with congenital forms of ichthyosis for whole metagenomics sequencing analysis.
RESULTS
Taxonomic profiling showed significant shifts in bacteria and fungi abundance and sporadic viral increases across ichthyosis subtypes. Cutibacterium acnes and Malassezia were significantly reduced across body sites, consistent with skin barrier disruption and depletion of lipids. Microbial richness was reduced, with specific increases in Staphylococcus and Corynebacterium genera, as well as shifts in fungal species, including Malassezia. Malassezia globosa was reduced at all body sites, whereas M. sympodialis was reduced in the ichthyotic upper arm and upper buttocks. Malassezia slooffiae, by contrast, was strikingly increased at all body sites in participants with congenital ichthyosiform erythroderma (CIE) and lamellar ichthyosis (LI). A previously undescribed Trichophyton species was also detected as sporadically colonizing the skin of patients with CIE, LI and epidermolytic ichthyosis subtypes.
CONCLUSIONS
The ichthyosis skin microbiome is significantly altered from healthy skin with specific changes predominating among ichthyosis subtypes. Skewing towards the Th17 pathway may represent a response to the altered microbial colonization in ichthyosis. What is already known about this topic? The skin microbiome of congenital ichthyoses is largely unexplored. Microbes play an important role in pathogenesis, as infections are common. The relative abundances of staphylococci and corynebacteria is increased in the cutaneous microbiome of patients with Netherton syndrome, but extension of these abundances to all congenital ichthyoses is unexplored. What does this study add? A common skin microbiome signature was observed across congenital ichthyoses. Distinct microbiome features were associated with ichthyosis subtypes. Changes in microbiome may contribute to T helper 17 cell immune polarization. What is the translational message? These data provide the basis for comparison of the microbiome with lipidomic and transcriptomic alterations in these forms of ichthyosis and consideration of correcting the dysbiosis as a therapeutic intervention.
Topics: Adult; Humans; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Ichthyosis, Lamellar; Lipids; Microbiota; Skin
PubMed: 35633118
DOI: 10.1111/bjd.21687