Form Of Ichthyosis Research Articles

Strategies for Differential Diagnosis and Management of Ichthyosis in Newborns

Congenital ichthyosis represents agroup of heterogeneous inherited skin diseases characterized by generalized keratinization disorder in the form of hyperkeratosis, caused by abnormalities in epidermal differentiation. The neonatal period is crucial for patients with ichthyosis due to the risk of developing complications, comorbidities, and fatal outcomes. Most complications arise from impaired skin barrier function. This article discusses the manifestations of ichthyosis in newborns, describes risks and complications, and suggests strategies for monitoring and treating patients. Purpose of the study: to present contemporary data on differential diagnosis and treatment strategies for newborn patients with congenital ichthyosis. Materials and Methods: review of Russian and international sources dedicated to the etiology, diagnosis, and treatment of ichthyosis was conducted. Results: Differential diagnosis of ichthyosis in the neonatal period is acrucial task, hence the most life-threatening subtypes are considered. The most severe progression with ahigh risk of fatal outcomes is characteristic of Harlequin ichthyosis. Collodion baby presents with less pronounced symptoms, is not afinal diagnosis, and may later develop clinical manifestations typical of ichthyosiform erythroderma, lamellar ichthyosis, or self-resolving congenital ichthyosis. Netherton syndrome is characterized by acombination of congenital ichthyosis with structural abnormalities of the hair shaft and apropensity for atopy. Epidermolytic ichthyosis, accompanied by the formation of blisters and erosions on the skin, requires differential diagnosis not only with other forms of ichthyosis but also with bullous epidermolysis, staphylococcal scalded skin syndrome, and toxic epidermal necrolysis. Every newborn with described manifestations requires support from amultidisciplinary team of specialists and timely therapeutic and diagnostic measures aimed at preventing the development of complications and deterioration of the patient’s condition. Conclusion: An analysis of global literature data and the practical experience of the authors indicate the complexities of differential diagnosis of ichthyosis forms in the neonatal period. To improve skin condition, prevent infectious complications, and correct electrolyte and respiratory disturbances, symptomatic treatment should begin before adefinitive diagnosis is established.

ORAL RETINOID TREATMENT IN A NEWBORN WITH LAMELLAR ICHTHYOSIS

Ichthyosis is a heterogeneous group of conification disorders characterized by hyperkeratosis involving the skin. One form of ichthyosis, lamellar ichthyosis (LI), is autosomal recessively inherited with an incidence of 1/300,000. The diagnosis is based on clinical findings, skin biopsy and genetic analysis. Treatment includes moisturizing the skin, reducing fluid loss and keratolytics. Oral retinoids have been found to be very successful in the treatment of LI(1). In this case, a premature newborn diagnosed with LI is presented because of its rarity and good response to oral retinoid treatment.

CLINICAL AND MOLECULAR GENETIC ASPECTS OF STRÜMPEL'S HEREDITARY SPASTIC PARAPLEGIA IN UZBEKISTAN

The research work is based on a prospective and retrospective observation of 95 patients with hereditary spastic paraplegia (HSP), who constituted the main group. Among the examined patients of the main group, there were 58 (61%) boys and 37 (39%) girls. The average age in the main group was 7.8±0.48 years. All patients complained of limb weakness of varying degrees, gait disturbance. The age gradation of the patients ranged from 2 years to 15 years. When studying the pedigrees of patients with HSP, in 34 cases the marriage was related, which amounted to 35.7%. It was found that in 48% of cases (27 families) there were patients with a similar disease in families. During the clinical and neurological examination of patients with HSP, we revealed both pure spastic paraplegia, characterized only by motor disorders (82.1%), and spastic paraplegia with complications (17.8%) in the form of impaired craniocerebral insufficiency, dysfunction of the pelvic organs (7.3%), a history of seizures (5.2%), polyneuropathies (11.5%), extraneural symptoms were detected in 3 (3.1%) patients, i.e. congenital skin changes in the form of ichthyosis. In 2 patients with uncomplicated HSP, whole genome sequencing in the SPAST/SPG4 gene was performed; in both cases, homozygous carriage of pathogenic autosomal dominant mutations chr2:32369901CAT>C and c.1617-105 T>C in the coding region of the SPG4 gene in exon 15 responsible for for the synthesis of the protein spastin in the nervous system.

A case Report On ichthyosis Vulgaris

Introduction: Ichthyosis is a rare skin condition that primarily affects the trunk or extremities, omitting the flexural areas of the body, and is characterized by dry, fish-like scales (Dahl, 2019). There are around 20 different forms of ichthyosis, the most prevalent of which is hereditary ichthyosis Vulgaris, which often manifests in the first year of life.Acquired variants of the skin condition can be brought on by several thyroid-related systemic problems, exposure to H.I.V., or Hodgkin's lymphoma. Numerous drugs, including herbal remedies for calming beverage kava, might potentially cause it.Present medical history: A 15-year female patient registered to the Skin ward (Dermat) with the main complaint of Skin that is dry, itchy, and scaly, especially on the arms all over the body. Skin that is tense, especially after a bath. Following a general check and study, ichthyosis Vulgaris was diagnosed. The most commonly prescribed treatment intervention and its consequences. The doctor interpreted Ichthyosis Vulgaris. Following a thorough examination and inquiry.Conclusion:-The following is the proposed structured symptom-based and evidence-based approach: strategy includes a guide to ichthyosis Vulgaris diagnosis and treatment. Its goal is to increase awareness about the importance of early detection and treatment of this ailment to enhance your quality of life while avoiding potential problems.

Development of metastatic inguinal squamous cell carcinoma in a patient with Netherton syndrome: A case report

Introduction: Netherton syndrome (NS) is a rare multisystem disorder with both cutaneous and extra-cutaneous manifestations. The syndrome includes the presence of congenital ichthyosis, exhibited by hyperkeratosis and abnormal skin scaling over the entire body. In rare instances, NS has been associated with the development of squamous cell carcinoma (SCC). Case Report: A 54-year-old male with a history of NS and recurrent squamous cell carcinoma presented with an enlarging left inguinal mass. Biopsy of the mass was positive for a new invasive squamous cell carcinoma with regional lymph node involvement and invasion of the left femoral vein. The patient underwent wide local resection, superficial and deep regional lymph node dissection, and resection of the left femoral vein. His hospital course was further complicated by multiple infections and progression of his cancer. He eventually transitioned to hospice care before receiving any additional treatment for his malignancy. Conclusion: This case highlights a patient with NS and a history of recurrent inguinal squamous cell carcinoma. Further investigation is needed to better highlight the complexity of factors associated with the development of squamous cell carcinoma in patients with NS and other forms of ichthyoses.

Ichthyosis and hereditary cornification disorders in dogs.

The stratum corneum (SC), the outermost layer of the epidermis, serves a crucial role in maintaining body hydration and protection from environmental insults. When the stratum corneum is injured or when the genetic blueprints are flawed, the body is at risk of dehydration, secondary infections and allergen sensitization. Advancements in veterinary dermatology have revealed a wide gamut of disease from relatively benign to lethal that specifically arise from flawed structural proteins, enzymes or lipids needed to create the corneocytes and lipid bilayers of the SC. Some conditions closely mimic their human counterparts while others are unique to the dog. This review will focus on forms of ichthyosis in the dog.

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

Background: Ichthyoses are a large group of hereditary cornification disorders, which are both clinically and etiologically heterogeneous and affect mostly all the skin surface of the patients. Ichthyosis has its origin in an ancient Greek word “ichthys” meaning fish, this is because the ichthyosis patients have dry, thickened, and scaly skin. There is an excess accumulation of epidermal cells resulting in the appearance of continuous and widespread scales on the body. There are many varieties of ichthyosis with a broad spectrum of intensity, severity, and associated symptoms, most of them are extremely rare. Ichthyosis vulgaris is the most frequently occurring type of ichthyoses. Method: The present study consists of four Pakistani ichthyosis families (A, B, C, and D). Whole exome sequencing (WES) approach was used to identify the pathogenic sequence variants in probands. The segregation of these variants in other participants was confirmed by Sanger sequencing. Results: Total four variants including, two splice site (TGM1: c.2088 + 1G > A) and (SPINK5: c.882 + 1G > T), a missense (SULT2B1: c.419C > T; p. Ala140Val), and a nonsense (FLG: c.6109C > T; p. Arg2037Ter) variant were identified in families A, C, B, and D, respectively, as causative mutations responsible for ichthyosis in these families. Conclusion: Our study unravels the molecular etiology of the four Pakistani ichthyosis families and validates the involvement of TGM1, SULT2B1, SPINK5, and FLG, in the etiology of different forms of ichthyosis. In addition, this study also aims to give a detailed clinical report of the studied ichthyosis families.

Genetic Study of X-Linked Recessive Ichthyosis in Eastern Ukraine

X-linked recessive ichthyosis (OMIM 308100) is a form of ichthyosis caused by abnormal keratinization and can result in disability, social maladaptation, and decreased quality of life for patients and their families. In most cases the disease is caused by a complete or partial deletion of the steroid sulfatase (STS) gene. This study estimated the prevalence of X-linked recessive ichthyosis, the inbreeding coefficient (or fixation index) FST, and the selection coefficient in individuals of eastern Ukraine (namely, Kharkiv oblast). The genealogical method was used to assess the genetic structure of families with a history of this disease. Fluorescent in situ hybridization (FISH) was carried out to detect the deletion of the STS gene in patients and their relatives. The prevalence of the disease in eastern Ukraine was 1.5 × 10–4 males, it ranged from 4.9 × 10–5 to 4.9 × 10–4 males in the districts, and from 2.2 × 10–4 males in the town of Krasnograd to 3.7 × 10–3 males in a village of Balakliia district. The burden of X-linked recessive ichthyosis was found to be positively correlated with the inbreeding coefficient FST in all the studied districts (r = 0.976). Over the past 10 years, the inbreeding coefficient FST increased 1.8 times and the prevalence of X-linked recessive ichthyosis increased 1.4–4.3 times in most districts of the region. The clinical genealogical analysis of nine large families revealed no females with X-linked recessive ichthyosis among relatives of probands, while 21.4% (n = 14) of the first-degree male relatives and 12.0% (n = 25) of the second-degree male relatives had ichthyosis. In most patients and their mothers from eastern Ukraine, FISH detected an interstitial deletion of the STS gene, ish del(X)(p22.31p22.31)(STS-), but no KAL1 gene deletions. In men with X-linked recessive ichthyosis, the average number of children per person was 2.5 times lower than in healthy relatives, and their offspring was characterized by the prevalence of females over males in a 3 : 1 ratio. In obligate heterozygous females, the average number of children per person was 2.2, and the sex ratio in the offspring approached 1 : 1.

Types of congenital nonsyndromic ichthyoses.

Congenital ichthyoses are a very heterogeneous group of diseases manifested by dry, rough and scaling skin. In all forms of ichthyoses, the skin barrier is damaged to a certain degree. Congenital ichthyoses are caused by various gene mutations. Clinical manifestations of the individual types vary as the patient ages. Currently, the diagnosis of congenital ichthyoses is based on molecular analysis, which also allows a complete genetic counseling and genetic prevention. It is appropriate to refer the patients to specialized medical centers, where the cooperation of a neonatologist, a pediatric dermatologist, a geneticist and other specialists is ensured.

Molecular Genetics of Keratinization Disorders - What's New About Ichthyosis.

The heritable forms of keratinization disorders, including various forms of ichthyosis and keratodermas, comprise a phenotypically heterogeneous group of diseases which can be divided into syndromic and non-syndromic forms. In the non-syndromic forms, the clinical manifestations are limited to the cutaneous structures while the syndromic ones are associated with a spectrum of extracutaneous manifestations. The inheritance in different families can be autosomal dominant, autosomal recessive or either X-linked dominant or recessive. Currently at least 67 distinct genes have been associated with different forms of ichthyosis. These genes can be grouped on the basis of their physiological involvement, including genes encoding structural components of epidermis, those involved in epidermal lipid metabolism, or those critical for cell-cell adhesion, and keratinocyte differentiation. This overview highlights some of the recent progress made in understanding the molecular genetics of keratinization disorders, and presents selected, recently characterized cases as representative of different forms of heritable ichthyosis.

Harlequin ichthyosis: a rare genetic dermatosis in Nigeria

Harlequin ichthyosis (HI) is a rare genetic skin disorder characterized by dry, thickened, scaly, fish-like skin with an autosomal recessive inheritance pattern. It is the severest form of ichthyosis and is associated with poor survival. We report a case of HI that presented to our facility and highlight the challenges associated with the management of this condition in our environment.

Features of quantitative indicators of finger and palmar dermatoglyphics in males and females with ichthyosis

Heterogeneity by types of genodermatoses inheritance from the group of ichthyosis, which include virtually all possible variants, is the basis for the application of one of the genetic methods of human study - the method of dermatoglyphics. The purpose of the study is to determine the peculiarities of the quantitative indexes of finger and palmar dermatoglyphics in men and women with ichthyosis. Dermatological examination was performed in 49 patients with ichthyosis and 136 dermatologically healthy persons. The sample of patients was conducted randomly. All persons received informed consent for conducting observations. Fingerprint and palm prints are obtained by scanning fingerprints on paper by the Futronic's FS8 USB2.0 Fingerprint Scanner using the ftrScanApiEx.exe program, and then transferring data to a personal computer. Processing of dermatoglyphics data was carried out according to the method of Cummins H. and Midlo Ch. (1961). The quantitative indices of both finger and palmar dermatoglifics were determined. The calculation of the received results was carried out in the licensed software package “Statistica 5.5”. The average sample values (M) and dispersion (σ) were determined in the groups of the subjects surveyed. Using the Mann-Whitney U-test determined the probability of differences in the results obtained for individual groups. A certain complex of quantitative signs of palmar dermatoglyphics is revealed, which is characteristic for men suffering from ichthyosis, which includes indexes of the intensity of the comb formations, the value of the length of the segment c-t, the value of the palm corners and the Cummins index. In women suffering from ichthyosis, such a complex includes, as in men, indicators of the intensity of the combs and the length of the segment c-t, except for which - also the value of palm comb accounts. Given the specific lamellar form of ichthyosis, the dermatoglyphic picture (monomorphism of established signs on both hands: the presence of a single 4-finger flexural fold, a pattern in the III interdigital gap, low localization of the carpal angle atd, and the presence of the ulnar loop, complicated by the internal pattern on the III finger of the left and the IV the finger of the right hand brushes), the authors concluded that the study of ichthyosis should be carried out necessarily for each form of ichthyosis separately, which significantly increases the resolution of the method of dermatoglyphics.

Study of prevalence of different forms of ichthyosis in Kharkiv region

Ichthyosis is genetically and clinically heterogenic group of epidermis keratinization disorders. Its prevalence is geographically different. Aim. The aim of this research was to evaluate ichthyosis prevalence in Kharkiv region. Methods. The collection of clinical-genealogical history was carried out by the method of single registration of the proband on the basis of the Regional Clinical Dermatological and Venereological Health Center No. 1 and the Dermatovenerological Health Centers of the Kharkiv Region in 2017. Results. The ichthyosis prevalence in Kharkiv region was 2.5·10–4 in 2017. The ichthyosis prevalence varied from 6.7∙10‑5 in Krasnohrad district to 1.0∙10‑3 in Dvorichna district. The least prevalence was in the population of Vovchansk city (1.1∙10‑4) and the highest one was in the population of Dvorichna city (10.7∙10‑4). The differences between the prevalence of ichthyosis vulgaris in Kharkiv region in 2008-2017 were established. Conclusions. It was found that the decrease of ichthyosis prevalence in Kharkiv region was 1.6 times during last 10 years. This index for ichthyosis vulgaris was decreased 1.9 times at the same period. Monogenic dermatoses, as an example of ichthyosis, can be used both to monitor the burden of genetic disorders in the region and to solve the problems of general and personal genetic safety in the population.
 Keywords: ichthyosis vulgaris, X-linked recessive ichthyosis, prevalence.

799 Exome, genome, and cDNA sequencing reveal KDSR mutations cause two forms of ichthyosis and identify retinoids as pathogenesis-directed therapy

799 Exome, genome, and cDNA sequencing reveal KDSR mutations cause two forms of ichthyosis and identify retinoids as pathogenesis-directed therapy

Embryonic AP1 Transcription Factor Deficiency Causes a Collodion Baby-Like Phenotype

AP1 transcription factors are important controllers of gene expression in the epidermis, and altered AP1 factor function can perturb keratinocyte proliferation and differentiation. However, our understanding of how AP1 signaling changes may underlie or exacerbate skin disease is limited. We have shown that inhibiting AP1 factor function in suprabasal adult epidermis leads to reduced filaggrin levels and to a phenotype that resembles the genetic disorder ichthyosis vulgaris. We now show that inhibiting AP1 factor function during development in embryonic epidermis produces marked phenotypic changes including reduced filaggrin mRNA and protein levels, compromised barrier function, marked ultrastructural change, and enhanced dehydration susceptibility that resembles the phenotype observed in the flaky tail mouse, a model for ichthyosis vulgaris. In addition, the AP1 factor-deficient newborn mice display a collodion membrane phenotype that is not observed in flaky tail mice or in newborn individuals with ichthyosis vulgaris but is present in other forms of ichthyosis. This mixed phenotype suggests the need for a better understanding of the possible role of filaggrin loss and AP1 transcription factor deficiency in ichthyoses and collodion membrane formation.

Calpain 12 Function Revealed through the Study of an Atypical Case of Autosomal Recessive Congenital Ichthyosis

Congenital erythroderma is a rare and often life-threatening condition, which has been shown to result from mutations in several genes encoding important components of the epidermal differentiation program. Using whole exome sequencing, we identified in a child with congenital exfoliative erythroderma, hypotrichosis, severe nail dystrophy and failure to thrive, two heterozygous mutations in ABCA12 (c.2956C>T, p.R986W; c.5778+2T>C, p. G1900Mfs*16), a gene known to be associated with two forms of ichthyosis, autosomal recessive congenital ichthyosis, and harlequin ichthyosis. Because the patient displayed an atypical phenotype, including severe hair and nail manifestations, we scrutinized the exome sequencing data for additional potentially deleterious genetic variations in genes of relevance to the cornification process. Two mutations were identified in CAPN12, encoding a member of the calpain proteases: a paternal missense mutation (c.1511C>A; p.P504Q) and a maternal deletion due to activation of a cryptic splice site in exon 9 of the gene (c.1090_1129del; p.Val364Lysfs*11). The calpain 12 protein was found to be expressed in both the epidermis and hair follicle of normal skin, but its expression was dramatically reduced in the patient's skin. The downregulation of capn12 expression in zebrafish was associated with abnormal epidermal morphogenesis. Small interfering RNA knockdown of CAPN12 in three-dimensional human skin models was associated with acanthosis, disorganized epidermal architecture, and downregulation of several differentiation markers, including filaggrin. Accordingly, filaggrin expression was almost absent in the patient skin. Using exvivo live imaging, small interfering RNA knockdown of calpain 12 in skin from K14-H2B GFP mice led to significant hair follicle catagen transformation compared with controls. In summary, our results indicate that calpain 12 plays an essential role during epidermal ontogenesis and normal hair follicle cycling and that its absence may aggravate the clinical manifestations of ABCA12 mutations.

Resveratrol induces human keratinocyte damage via the activation of class III histone deacetylase, Sirt1.

Human skin diseases are various and induce chronic inflammatory disorders, including psoriasis, atopic dermatitis and certain forms of ichthyosis. Psoriasis is a chronic inflammatory skin disease characterized by circumscribed, red, thickened plaques. Regulation of the balance between growth, differentiation and death is critical to keratinocytes; when altered, epidermal keratinocytes undergo hyperproliferation, abnormal differentiation and inflammatory infiltration. In the present study, we focused on the effects of resveratrol, found in red wine and peanuts, on the cell death of keratinocytes. We additionally studied the mechanism of resveratrol on Sirt1, a class III histone deacetylase, and Akt phosphorylation. Resveratrol caused apoptosis and increased Sirt1 expression in human HaCaT keratinocytes, following a decrease in the p62 protein level. Inhibition of Sirt1 by Sirt1 inhibitor restored cell viability and protein levels. Furthermore, we showed that resveratrol-induced Sirt1 blocked Akt phosphorylation. The present results indicated that resveratrol inhibited the Akt pathways by inducing Sirt1, thus leading to cell death. These data suggest that resveratrol-mediated activation of Sirt1 histone deacetylase may be a potential therapeutic target for skin diseases including psoriasis.

Frequency of Ear Symptoms and Hearing Loss in Ichthyosis: A Pilot Survey Study

Ichthyoses comprise a heterogeneous array of skin conditions resulting from impairment of cornification. Although ear structures can be affected, ear-related symptoms have never been investigated in patients with ichthyosis. In this pilot survey study, our aim was to determine the frequency of ear symptoms, hearing loss, and related medical interventions in patients with ichthyosis. Our secondary aim was to compare the frequency of these items according to age group. An online survey using Redcap was developed and posted online on the Foundation for Ichthyosis and Related Skin Types website for 6 months. Patients or parents of patients with ichthyosis were asked to complete the survey. Data analysis excluded patients with keratitis-ichthyosis-deafness syndrome and surveys that had fewer than two completed items. One hundred thirty-five unique surveys were used for data analysis. Of all participants, 80% reported ear pruritus, 66% reported trouble hearing, 29% reported frequent ear pain, 28% had abnormal hearing test results, and 16% had used hearing aids. Of the 88 participants who reported trouble hearing, 24 (27.3%) had never been to a hearing specialist. Significantly more participants older than 18 years of age (74%, 57/77) reported trouble hearing than participants age 18 years and younger (53%, 31/58; p = 0.02). The frequencies of other ear symptoms and hearing loss were not statistically significantly different between the age groups. Ear pruritus, ear pain, and hearing loss are important concerns in patients with all forms of ichthyosis in all age groups. Early diagnosis and intervention may improve the quality of life of patients with ichthyosis.

Modèles spontanés de maladies humaines chez le chien : exemple des ichtyoses

Ichthyoses encompass a heterogeneous group of genodermatoses characterized by abnormal desquamation over the entire body due to defects of the terminal differentiation of keratinocytes and desquamation, which occur in the upper layer of the epidermis. Even though in humans more than 40 genes have already been identified, the genetic causes of several forms remain unknown and are difficult to identify in Humans. Strikingly, several purebred dogs are also affected by specific forms of ichthyoses. In the Golden retriever dog breed, an autosomal recessive form of ichthyosis, resembling human autosomal recessive congenital ichthyoses, has recently been diagnosed with a high incidence. We first characterized the disease occurring in the golden retriever breed and collected cases and controls. A genome-wide association study on 40 unrelated Golden retriever dogs, using the canine 49.000 SNPs (single nucleotide polymorphisms) array (Affymetrix v2), followed by statistical analyses and candidate gene sequencing, allowed to identify the causal mutation in the lipase coding PNPLA1 gene (patatin-like phospholipase domain-containing protein). Screening for alterations in the human ortholog gene in 10 autosomal recessive congenital ichthyoses families, for which no genetic cause has been identified thus far, allowed to identify two recessive mutations in the PNPLA1 protein in two families. This collaborative work between "human" and "canine" geneticists, practicians, histopathologists, biochemists and electron microscopy experts not only allowed to identify, in humans, an eighth gene for autosomal recessive congenital ichthyoses, but also allowed to highlight the function of this as-yet-unknown skin specific lipase in the lipid metabolism of the skin barrier. For veterinary medicine and breeding practices, a genetic test has been developed. These findings illustrate the importance of the discovery of relevant human orthologous canine genetic diseases, whose causes can be tracked in dog breeds more easily than in humans. Indeed, due to the selection and breeding practices applied to purebred dogs, the dog constitutes a unique species for unravelling phenotype/genotype relationships and providing new insights into human genetic diseases. This work paves the way for the identification of rare gene variants in humans that may be responsible for other keratinisation and epidermal barrier defects.

Complications of ichthyosis beyond the skin

Although ichthyoses are noted for their skin features, like many dermatologic conditions, patients are often impacted in ways beyond the skin. Much has been described in recent years regarding quality of life and skin disorders. This is certainly the case for ichthyosis. For neonates or others with diffuse involvement of their skin, nutritional needs are often exceeding normal requirements. These can often result in growth abnormalities. Lastly, with specific subtypes of ichthyosis, compromise of tissues around the eyes and ears can be of concern to some patients. Certainly, some forms of ichthyosis are routinely complicated by such findings. It is important for practitioners caring for individuals with ichthyosis to have these issues in mind.