Search

The human retroviral-like aspartic protease 1 (ASPRV1) is a retroviral-like protein that was first identified in the skin due to its expression in the stratum granulosum layer of the epidermis. Accordingly, it is also referred to as skin-specific aspartic protease. Similar to the retroviral polyproteins, the full-length ASPRV1 also undergoes self-proteolysis, the processing of the precursor is necessary for the autoactivation of the protease domain. ASPRV1’s functions are well-established at the level of the skin: it is part of the epidermal proteolytic network and has a significant contribution to skin moisturization via the limited proteolysis of filaggrin; it is only natural protein substrate identified so far. Filaggrin and ASPRV1 are also specific for mammalians, these proteins provide unique features for the skins of these species, and the importance of filaggrin processing in hydration is proved by the fact that some ASPRV1 mutations are associated with skin diseases such as ichthyosis. ASPRV1 was also found to be expressed in macrophage-like neutrophil cells, indicating that its functions are not limited to the skin. In addition, differential expression of ASPRV1 was detected in many diseases, with yet unknown significance. The currently known enzymatic characteristics—that had been revealed mainly by in vitro studies—and correlations with pathogenic phenotypes imply potentially important functions in multiple cell types, which makes the protein a promising target of functional studies. In this review we describe the currently available knowledge and future perspective in regard to ASPRV1. [ABSTRACT FROM AUTHOR]

Epidermal nevi are common benign cutaneous hamartomas that may rarely demonstrate histopathologic evidence of epidermolytic hyperkeratosis (EHK), representing cutaneous mosaicism for pathogenic keratin variants. Rarely, individuals with linear epidermal nevi transmit to their children the inherited form of EHK, also known as epidermolytic ichthyosis, characterized by generalized erythema, blistering, and scaling at birth evolving to widespread hyperkeratosis. We present an updated review of reported cases of linear epidermal nevi with EHK exhibiting transmission of epidermolytic ichthyosis to guide important considerations in the care of individuals with epidermal nevi. Clinical characteristics of linear epidermal nevi do not reliably predict the presence of EHK. All reported cases of transmission to offspring have occurred in individuals with linear epidermal nevi involving more than one anatomic area suggesting increased reproductive risk with involvement of two or more anatomic sites. Therefore, genetics consultation is recommended for these individuals with biopsy‐confirmed EHK. For individuals with smaller areas of epidermal nevus involvement, the implications are less well known, though genetics consultation may still be considered for those interested in further discussion of general reproductive risk. [ABSTRACT FROM AUTHOR]

Advancements in the molecular genetics of epidermolysis bullosa (EB) and ichthyosis, two rare inherited skin conditions, have enabled the identification of genetic variants that cause these diseases. Alongside technological advancements in genetic medicine, the identification of variants causal of these rare skin conditions has led to preclinical research and the clinical development of various in vivo and ex vivo gene and cell therapies for their treatment. Gene and cell therapies are considered to be the most advanced forms of personalized medicine, demonstrating safety and efficacy in numerous rare diseases. Although the orphan drug development boom has resulted in regulatory approval of multiple gene and cell therapies for various rare conditions, the application of these modalities to rare inherited skin conditions remains limited. Nonetheless, there are successful examples of both in vivo gene therapy- and ex vivo cell therapy-based approaches developed to treat EB and ichthyosis. This review highlights preclinical research and the clinical development of gene and cell therapies for multiple subtypes of these two devastating congenital skin conditions, including a gene therapy recently approved by the U.S. Food and Drug Administration for the treatment of recessive dystrophic EB. Plain Language Summary: Advances in genetics research for skin diseases such as epidermolysis bullosa and ichthyosis have led to the discovery of many new subtypes of these severe skin conditions. Identifying new subtypes has in turn led to new treatments for these conditions, including gene and cell therapies. Gene and cell therapies aim to address the underlying genetic causes of disease and have already shown success in the clinic. While the development of such treatments for rare skin diseases has been limited, there are notable examples of gene and cell therapies developed for epidermolysis bullosa and ichthyosis. This review highlights recent developments in gene and cell therapy for epidermolysis bullosa and ichthyosis, including a newly approved gene therapy for recessive dystrophic epidermolysis bullosa. [ABSTRACT FROM AUTHOR]

Objectives Escherichia coli can cause infections in the urinary tract and in normally sterile body sites leading to invasive E. coli disease (IED), including bacteraemia and sepsis, with older populations at increased risk. We aimed to estimate the theoretical coverage rate by the ExPEC4V and 9V vaccine candidates. In addition, we aimed at better understanding the diversity of E. coli isolates, including their genetic and phenotypic antimicrobial resistance (AMR), sequence types (STs), O-serotypes and the bacterial population structure. Methods Blood and urine culture E. coli isolates (n  = 304) were collected from hospitalized patients ≥60 years (n = 238) with IED during a multicentric, observational study across three continents. All isolates were tested for antimicrobial susceptibility, O-serotyped, whole-genome sequenced and bioinformatically analysed. Results A large diversity of STs and of O-serotypes were identified across all centres, with O25b-ST131, O6-ST73 and O1-ST95 being the most prevalent types. A total of 45.4% and 64.7% of all isolates were found to have an O-serotype covered by the ExPEC4V and ExPEC9V vaccine candidates, respectively. The overall frequency of MDR was 37.4% and ST131 was predominant among MDR isolates. Low in-patient genetic variability was observed in cases where multiple isolates were collected from the same patient. Conclusions Our results highlight the predominance of MDR O25b-ST131 E. coli isolates across diverse geographic areas. These findings provide further baseline data on the theoretical coverage of novel vaccines targeting E. coli associated with IED in older adults and their associated AMR levels. [ABSTRACT FROM AUTHOR]

Introduction: Kava, a substance derived from the Piper methysticum plant, is enjoying a surge in popularity in the United States due to its purported anxiolytic and analgesic effects. Though ichthyosiform dermopathy is a known adverse effect associated with chronic kava exposure in adults, dermopathy in a newborn due to maternal kava use has not yet been described. Case Report: This is a case of a 41-year-old woman who was taking a combination kava/kratom product throughout her pregnancy. She developed an ichthyosiform dermopathy that resolved after she stopped using the product postpartum. Her male infant had a neonatal course complicated by both neonatal opioid withdrawal syndrome, attributed to maternal kratom and buprenorphine use, as well as a diffuse ichthyosiform rash similar to descriptions of kava ichthyosiform dermopathy in adults. His neonatal course was complicated by Group B streptococcus and Serratia marscecens bacteremia (treated with antibiotics) and seizures (treated with lorazepam and phenobarbital). His rash resolved completely by day of life 22. At 9-month outpatient follow-up, he had no dermatologic abnormalities or rash recurrence. Discussion: Maternal kava use during pregnancy may cause fetal dermopathy presenting as an acquired ichthyosis. More public education is needed about the potential consequences of kava use, particularly during pregnancy. [ABSTRACT FROM AUTHOR]

Background No efficient treatment has yet been established for epidermolytic ichthyosis (EI), which is caused by pathogenic variants of KRT1 or KRT10. Patients with ichthyosis with confetti (IWC) have multiple normal-appearing spots, caused by the revertant somatic recombination of pathogenic variants that occurs at each spot independently. Additionally, some patients with EI have large areas of normal skin due to revertant postzygotic mosaicism. Objectives To assess the feasibility of transplanting cultured epidermal autografts (CEAs) produced from revertant epidermal keratinocytes in patients with EI and IWC. Methods We performed a clinical trial of treatment with CEAs produced from each patient's own revertant epidermal keratinocytes as a proof-of-concept study. This was a single-arm, open, unmasked, uncontrolled, single-assignment, treatment-purpose study. The primary outcome was the percentage area that lacked recurrence of ichthyosis lesions 4 weeks after the final transplant. The secondary outcome was the percentage area lacking recurrence of ichthyosis lesions 24 weeks after the initial transplantation. The trial was registered with the Japan Registry of Clinical Trials (jRCTb041190097). Results We successfully produced CEAs from genetically confirmed revertant skin from two patients with mosaic EI and from one patient with IWC and confirmed by amplicon sequencing and droplet digital polymerase chain reaction analysis that the CEAs mainly consisted of revertant wild-type cells. Single-cell RNA sequencing analysis confirmed the normal proliferation and safety profiling of CEAs. CEAs were transplanted onto desquamated lesional sites in the patients. Four weeks post-transplantation, the percentage area lacking recurrence of ichthyosis lesions in the three patients was 40%, 100% and 100% respectively, although recurrence of ichthyosis lesions was seen at the site of CEA transplantation in all three patients at 24 weeks post-transplantation. Conclusions CEAs from normal skin have the potential to be a safe and local treatment option for EI and IWC. [ABSTRACT FROM AUTHOR]

Background: Patients with inherited ichthyosis suffer from scaling due to mutations affecting the epidermal barrier. Symptomatic treatment with ointments, bathing and mechanical scale removal can alleviate the disease, but therapy is time and cost intensive. Objectives: We investigated costs, time and disease burden of ichthyoses. The study addresses difficulties of the healthcare situation for patients with ichthyoses and reveals potential improvements. Materials and Methods: We developed a questionnaire addressing time and financial effort for the treatment. Additionally, we collected data of the Dermatology Life Quality Index (DLQI) and the Pruritus Life Quality (5PLQ) questionnaires to determine the impact of ichthyosis and associated pruritus on quality of life (QoL). Results: We recruited 144 patients with ichthyosis (median age: 23; 53.5% female) from the Department of Dermatology in Muenster (Germany) and the German patient support group including common, rare and syndromic subtypes. Eighty‐seven percent reported applying topical therapeutics at least once per day, 66.4% several times with an overall median duration of 15 min. Highest single expenditure of time was due to balneotherapy (n = 115; median bathing time: 40 min). In 81.9%, the health insurance did not completely cover the costs for topical treatment causing additional financial burden to the patient with a median of 71 € per quarter, herein creams being the largest cost factor (50 €). Patients with Netherton syndrome showed the highest median expenditure (170 €). The QoL impairment under treatment was moderate (median DLQI: 8.5 points). Pruritus was prevalent in 79.9% and showed a distinct impact on QoL (median 5PLQ: 7.5 points) without any significant difference between the subtypes (p = 0.37). Conclusion: Patients suffering from ichthyoses have a large and lifelong overall burden in mild and severe subtypes. Since continuous topical treatment is required, financial and psychosocial support needs to be considered beyond dermatological care. [ABSTRACT FROM AUTHOR]

Background Hypothesis/Objectives Animals Materials and Methods Results Conclusions and Clinical Relevance Autosomal recessive ichthyosis leads to structural or biochemical changes that impair skin barrier function.To assess (1) the phenotype and genotype in a litter of Jack Russell Terriers with autosomal recessive congenital ichthyosis (ARCI), and (2) the defective skin barrier and determine if a topical ceramide can modulate the barrier.A healthy dam and litter of Jack Russell Terrier puppies (healthy male, affected male and female), one affected adult Jack Russell Terrier and one unrelated healthy Jack Russell Terrier.A severe cornification defect was identified via examination of affected puppies. As the phenotype worsened, the affected puppies received a topical application of ω‐0‐acylceramide for 10 days. Before humane euthanasia, the skin barrier was evaluated via transepidermal water loss (TEWL), corneometry and pH in affected dogs. Genomic testing was performed, and skin samples were analysed by light and electron microscopy.Affected puppies were homozygous for the 1980 bp LINE‐1 insertion in the TGM1 (transglutaminase 1) gene; the unaffected littermate and the dam were heterozygous carriers. ARCI puppies were underweight and had a severe hyperkeratotic phenotype that impaired mobility. TEWL was markedly higher in affected dogs. The cutaneous pH of affected puppies was higher than the normal littermate. Treatment of the skin with ω‐0‐acylceramide normalised the pH to match the littermate and decreased TEWL. Electron microscopy revealed marked attenuation of the cornified envelope.Dogs with TGM1‐deficient ARCI have an impaired skin barrier. Topical therapy can partially repair the barrier defect. [ABSTRACT FROM AUTHOR]

Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous disorder with aberrant skin scaling and increased transepidermal water loss (TEWL). Current treatments for ARCI are limited and suboptimal. We present the case of a 27-year-old man with ARCI resulting from a homozygous missense variant in TGM1. RNA-sequencing of lesional skin revealed aberrant Janus kinase–signal transducer and activator of transcription signalling, providing a rationale for innovative treatment with a Janus kinase inhibitor. We prescribed oral tofacitinib (11 mg daily) for 26 weeks. Rapid improvements in erythema and fissuring occurred within the first month. Sustained reductions in 5-D itch scale and Dermatology Life Quality Index scores were also observed. TEWL decreased for the first 10 weeks but increased thereafter. Tofacitinib downregulated inflammatory genes and pathways, while enhancing skin barrier markers. Moreover, transglutaminase 1 distribution was normalized although enzymatic activity remained deficient. This study suggests that oral tofacitinib may be a useful therapy to consider for patients with ARCI. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate how diagnostic practice in congenital ichthyoses has evolved during the years 2000–2020 and what kind of gene variants of congenital ichthyosis have been found. Methods: The study cohort of this register‐based research consisted of a total of 88 patients, whose diagnostic testing was conducted, and ichthyosis diagnoses set at the Department of Dermatology and the Department of Clinical Genetics at Tampere University Hospital during the years 2000–2020. Results: Diagnosis of ichthyosis was confirmed with genetic testing in 33 cases, and with conventional diagnostic methods, such as clinical findings, skin biopsy and family history of ichthyoses, in 55 cases. We observed four novel variants in patients with the clinical diagnoses of congenital ichthyoses. Conclusion: When genetic testing became available, it was offered primarily to patients with severe forms of ichthyosis. During the study period next‐generation sequencing became the genetic testing method of choice providing new opportunities in diagnostics. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Cutaneous scaling and associated clinical syndrome displayed in X‐linked ichthyosis mandates multidisciplinary care. Patient with ichthyosis confronts a numerous challenge to an anesthesiologist and demands a rigorous management. As these patients are very vulnerable perioperatively, meticulous care and support are utmost. Ichthyosis is a group of genetic conditions distinguished by the appearance of hyperkeratotic scales on the skin's surface. X‐linked ichthyosis results from a mutation in the steroid sulfatase (STS) gene, which encodes the steroid sulfatase enzyme. Here we report a case of a 6‐year‐old child with X‐linked ichthyosis. He presented to our operation theater for correction of left‐sided undescended testis and underwent surgery uneventfully. To handle X‐linked ichthyosis perioperatively, meticulous planning and efficient anesthetic administration are critical. [ABSTRACT FROM AUTHOR]

Abstract Advancements in the molecular genetics of epidermolysis bullosa (EB) and ichthyosis, two rare inherited skin conditions, have enabled the identification of genetic variants that cause these diseases. Alongside technological advancements in genetic medicine, the identification of variants causal of these rare skin conditions has led to preclinical research and the clinical development of various in vivo and ex vivo gene and cell therapies for their treatment. Gene and cell therapies are considered to be the most advanced forms of personalized medicine, demonstrating safety and efficacy in numerous rare diseases. Although the orphan drug development boom has resulted in regulatory approval of multiple gene and cell therapies for various rare conditions, the application of these modalities to rare inherited skin conditions remains limited. Nonetheless, there are successful examples of both in vivo gene therapy- and ex vivo cell therapy-based approaches developed to treat EB and ichthyosis. This review highlights preclinical research and the clinical development of gene and cell therapies for multiple subtypes of these two devastating congenital skin conditions, including a gene therapy recently approved by the U.S. Food and Drug Administration for the treatment of recessive dystrophic EB.

A clinical case of ocular surface xerosis in a patient with previously undiagnosed skin ichthyosis is presented. Clinical manifestations of change occurring in the eyes of the patient disease are outlined, and a complex of therapeutic measures to maintain the eye surface in ichthyosis is proposed.

Background and Objectives: Juvenile autoimmune hepatitis (AIH) is an inflammatory, immune-mediated liver disease that affects individuals from infancy to adolescence. The clinical presentation of AIH can mimic other hepatic disorders, such as viral hepatitis, toxic hepatitis, and Wilson's disease, often manifesting with symptoms like fatigue, nausea, vomiting, jaundice, fever, and pruritus.Case Presentation: A 16-year-old male with a history of congenital ichthyosis, xerosis cutis, mild intermittent asthma, and environmental allergic rhinitis presented to the clinic with upper respiratory symptoms. Upon examination, the patient was found to be jaundiced, prompting an urgent referral for further evaluation. This led to a diagnosis of autoimmune hepatitis and inflammatory bowel disease.Discussion: Juvenile autoimmune hepatitis is a rare but serious inflammatory liver disorder that primarily affects infants and adolescents. Due to its similarities with various other liver diseases, differential diagnosis can be quite challenging. Overall, the prognosis for our patient appears to be positive.

Palmoplantar keratoderma (PPK) is a hereditary cutaneous disorder characterized by a marked hyperkeratosis of the palms and soles. A variant that was inherited in an autosomal dominant form was highlighted in a 20-month-old girl-child. The proband was brought to the Paediatric Outpatient Department by her mother because of an unusual but a familiar thickening of the palms and soles, having married to the proband’s father who is having a similarly thickened palms and soles. The disorder was noticed in the proband, two weeks after birth, initially with reddening of the palms and soles, followed by blistering and eventual thickening of the palms and soles, occurring over one-and-half months. There were no associated systemic symptoms and the hair, the teeth and nails were not affected. PPK, although a common cutaneous disorder, has been reported sparingly in Nigeria. The index case was diagnosed histologically to be the nonepidermolytic type and a high dose of vitamin A and salycylic acid ointment were administered with a little improvement in the keratoses.

Rationale: Lepromatous leprosy can have many atypical presentations, obscuring early diagnosis. We present a case of lepromatous leprosy, presenting with atypical features, which made a diagnostic dilemma. Patient concerns: A 48-year-old man presented with bilateral lower limb oedema and scaly “ichthyosis like” skin rash in both hands and feet, hepatosplenomegaly and pancytopenia, over a course of three months, without any classical features of leprosy. A skin biopsy revealed an unexpected diagnosis of borderline lepromatous leprosy. Diagnosis: Lepromatous leprosy. Interventions: Multi-drug regimen treatment with rifampicin, dapsone and clofazimine for lepromatous leprosy. Outcomes: The patient made a good clinical recovery. Lessons: In endemic settings, clinicians should be aware of similar atypical manifestations of leprosy to face the global challenge of eradicating this chronic deforming disease.

Background: The etiology of nephrotic syndrome can vary, with underlying metabolic diseases being a potential factor. Cobalamin C (cblC) defect is an autosomal recessive inborn error of metabolism caused by mutations in the MMACHC gene, resulting in impaired vitamin B12 processing. While cblC defect typically manifests with hematological and neurological symptoms, renal involvement is increasingly recognized but remains rare. Case Presentation: We describe a 7-month-old male patient presenting with fatigue and edema. His first laboratory findings showed anemia, thrombocytopenia, hypoalbuminemia and proteinuria and further examinations reveals hemolysis in peripheric blood smear. During his follow up respiratory distress due to pleural effusion in the right hemithorax was noticed. And fluid leakage to the third spaces supported nephrotic syndrome diagnosis. The patient's condition deteriorated, leading to intensive care admission due to, hypertensive crisis, and respiratory distress. High total plasma homocysteine and low methionine levels raised suspicion of cobalamin metabolism disorders. Genetic testing confirmed biallelic MMACHC gene mutations, establishing the diagnosis of cblC defect. Treatment with hydroxycobalamin, folic acid, and betaine led to remarkable clinical improvement. Discussion/Conclusion: This case underscores the significance of recognizing metabolic disorders like cblC defect in atypical presentations of nephrotic syndrome. Early diagnosis and comprehensive management are vital to prevent irreversible renal damage. While cblC defects are more commonly associated with atypical hemolytic uremic syndrome, this case highlights the importance of considering cobalamin defects in the differential diagnosis of nephrotic syndrome, especially when associated with accompanying findings such as hemolysis. Our case, which has one of the highest homocysteine levels reported in the literature, emphasizes this situation again. [ABSTRACT FROM AUTHOR]

Background: Owing to the highly contagious nature of SARS-CoV-2, the use of personal protective equipment (PPE) among the healthcare workers (HCWs) is mandatory. However, PPE associated adverse effects are also there. Objective: To study the adverse effects associated with PPE and their preventive measures amongst the HCWs. Material and Methods: A descriptive study was conducted among 200 HCWs working in a Covid center of a tertiary care center. The participants were sent the questionnaires online. Some of them not having smart phones were interviewed telephonically. Their information profile, the various adverse effects associated with PPE, and the preventive measures being practiced by them were noted. Data was analyzed using descriptive and inferential statistics. Results: Total 97% HCWs reported adverse effects with hazmat suit; 96% with N 95 mask; 92% with goggle and 78% with gloves. The adverse effects associated with the prolonged use of the mask were erythema; erosions and scar at the nasal bridge; ear pain; difficulty in breathing; and headache. Sixty-seven percent of the participants had sweating with the use of gloves, which led to cutaneous exfoliation such as dry hands (55%) and skin itching (43%). Moisturizers and natural oils were used to prevent the dryness of hands. For the pressure related injury over the nasal bridge due to N95 mask, participants used to apply Band-Aid (adhesive bandage) and cotton dressing. Conclusion: Adverse skin reactions related to PPE are common among HCWs. Comprehensive assessment of the skin condition and awareness on adverse skin reactions should be advocated. [ABSTRACT FROM AUTHOR]

Epidermolytic ichthyosis (EI) is an autosomal dominant genetic disease that is part of the keratinopathic ichthyosis (KPI) group (1). It affects 1 in every 200,000 to 300,000 newborns, resulting from a variant in the KRT1 or KRT10 gene that encodes keratin 1 and 10 respectively; proteins present in the keratinocytes of the suprabasal layers of the epidermis, where they form bundles of tonofibrils and serve as early markers of cellular differentiation (2). At birth, patients present erythroderma and blisters, due to the fragility of the cytoskeleton of the epidermal cells and the collapse of the keratin filaments. Skin changes evolve over time to hyperkeratosis (3). We present two cases of patients with EI, in which the genetic study played a key role in the specific diagnosis, helping to establish a targeted treatment, establish prognoses and asses the risk of heritability, bringing us closer to precision medicine. [ABSTRACT FROM AUTHOR]

Background: Ichthyosis is a diverse skin disease characterized by dry skin and itching, particularly affecting the hands. Most forms of this condition are hereditary. Objectives: In this study, we investigated potential new mutations associated with this disease using the new technique of whole-exome sequencing. Methods: In this study, after collecting the patient's blood sample in an EDTA tube and extracting DNA using the salting-out method, next-generation sequencing was performed using the WES method. Following the analysis of the results and identification of the candidate gene, PCR technique and Chromas software were used to confirm the findings. Results: The results indicated the presence of a new variant, NM_001099287: Exon 6:c.C1083A: p.Y361X, in the NIPAL4 gene in a heterozygous form in the parents and a homozygous form in the patient. This variant occurred as a nucleotide substitution in the exon 6 region of the NIPAL4 mRNA sequence. Conclusions: Using the WES technique, it is possible to investigate the presence of new variants related to ichthyosis in a short time and at a low cost. [ABSTRACT FROM AUTHOR]

Ichthyosis is a rare genetic skin disease that typically appears at birth or within the first few months of life. It is caused by mutations in some genes that interfere with the normal development of keratinocytes, causing thickening and peeling of the skin that resembles fish scales. The purpose of this study is to develop and evaluate a comprehensive, easy-to-use tool to measure the overall severity of body ichthyosis in adults and children. In this article an overview of several systems, among the most suitable and convenient, for assessing the severity of ichthyosis is provided. The use of a severity rating system in patient observation is also presented. [ABSTRACT FROM AUTHOR]

Aim: Skin barrier dysfunction can trigger various skin disorders in older adults. Skin barrier assessment is essential for nurses and caregivers to prevent skin disorders; however, the evidence available for clinical assessment is limited. This systematic review aimed to clarify the risk factors of skin barrier dysfunction in older adults. Methods: This review adhered to the Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines. The four databases were searched using multiple terms related to "aged" and "skin barrier." The search was initially run on April 19, 2023, and rerun on October 12, 2023. Peer‐reviewed quantitative studies in English were included, with no publication time limit being set. Two reviewers assessed the risk of bias in a blinded and independent manner using JBI tools. Owing to the heterogeneity of the results, a narrative synthesis was performed. Results: Among the database‐identified 4833 studies, 20 studies were included. The extracted factors were categorized as demographic characteristics, functional characteristics, chronic diseases, nutritional status, skin condition, and environmental factors. However, owing to high risk of bias and inconsistent results across studies, only chronic kidney disease and dry skin were considered risk factors for skin barrier dysfunction in older adults. Conclusions: Assessment of chronic kidney disease and dry skin in daily skin care may guide the development of personalized skincare programs to maintain skin integrity in older adults. Furthermore, cohort studies that consider confounding factors and the reliability of measurements are needed for an in‐depth investigation into skin barrier dysfunction and more risk factors. [ABSTRACT FROM AUTHOR]

Chanarin‐Dorfman syndrome (CDS) is a multisystem autosomal recessive disorder due to variants of the ABHD5 gene, characterized by lipid vacuoles in the liver and leukocytes, and possible involvement of eyes, ears, skeletal muscle, and central nervous system. CDS may present with skin changes, most commonly congenital non‐ bullous ichthyosiform erythroderma, however erythrokeratoderma‐like findings have been rarely reported in CDS patients. Herein, we report clinical, histopathological and genetic findings of four patients with CDS presenting with different clinical forms of erythrokeratoderma (three with progressive symmetric erythrokeratoderma‐like features and one with erythrokeratoderma variabilis (EKV)‐like features), including one patient with a novel mutation in ABHD5. Although the typical skin finding of CDS syndrome is reported as non‐bullous congenital ichthyosiform erythroderma, CDS should also be in the differential diagnosis in patients with EKV‐like lesions. [ABSTRACT FROM AUTHOR]

Congenital myasthenic syndrome-25 (CMS-25) is an autosomal recessive neuromuscular disorder caused by a homozygous mutation in VAMP1 gene. To date, only eight types of allelic variants in VAMP1 gene have been reported in 12 cases of CMS-25. Here, we report on an 8-year-old boy with motor developmental delay, axial hypotonia, myopathic face, muscle weakness, strabismus, ptosis, pectus carinatum, kyphoscoliosis, joint contractures, joint laxity, seizures, and recurrent nephrolithiasis. He also had feeding difficulties and recurrent aspiration pneumonia. Brain magnetic resonance imaging at 20 months of age showed left focal cerebellar hypoplasia. Genetic analysis revealed a homozygous missense variant of c.202C > T (p.Arg68Ter) in the VAMP1 gene. Treatment with oral pyridostigmine was started, which resulted in mild improvement in muscle strength. Salbutamol syrup was added a few months later, but no significant improvement was observed. This case report presents novel findings such as focal cerebellar hypoplasia and nephrolithiasis in VAMP1 -related CMS-25. Consequently, this case report extends the clinical spectrum. Further studies are needed to expand the genotype–phenotype correlations in VAMP1 -related CMS-25. [ABSTRACT FROM AUTHOR]

This article explores the topic of pediatric secondary osteoporosis, specifically focusing on vertebral fractures (VFs) and the importance of investigating osteoporosis in children with isolated back pain, as it may indicate underlying systemic diseases. The most common causes of secondary osteoporosis in children are endocrine disorders, gastrointestinal disorders, rheumatologic, oncologic, and renal diseases, medications such as glucocorticoids, and immobility. The diagnosis of childhood osteoporosis relies on dual-energy X-ray absorptiometry (DEXA) and conventional spine radiographs. The article presents two case studies that highlight the importance of early diagnosis and a multidisciplinary approach involving radiologists, pediatricians, and orthopedics in recognizing and treating underlying systemic diseases. [Extracted from the article]

Steroid sulphatase (STS) cleaves sulphate groups from steroid hormones, and steroid (sulphate) levels correlate with mood and age‐related cognitive decline. In animals, STS inhibition or deletion of the associated gene, enhances memory/neuroprotection and alters hippocampal neurochemistry. Little is known about the consequences of constitutive STS deficiency on memory‐related processes in humans. We investigated self‐reported memory performance (Multifactorial Memory Questionnaire), word‐picture recall and recent mood (Kessler Psychological Distress Scale, K10) in adult males with STS deficiency diagnosed with the dermatological condition X‐linked ichthyosis (XLI; n = 41) and in adult female carriers of XLI‐associated genetic variants (n = 79); we compared results to those obtained from matched control subjects [diagnosed with ichthyosis vulgaris (IV, n = 98) or recruited from the general population (n = 250)]. Using the UK Biobank, we compared mood/memory‐related neuroanatomy in carriers of genetic deletions encompassing STS (n = 28) and non‐carriers (n = 34,522). We found poorer word‐picture recall and lower perceived memory abilities in males with XLI and female carriers compared with control groups. XLI‐associated variant carriers and individuals with IV reported more adverse mood symptoms, reduced memory contentment and greater use of memory aids, compared with general population controls. Mood and memory findings appeared largely independent. Neuroanatomical analysis only indicated a nominally‐significantly larger molecular layer in the right hippocampal body of deletion carriers relative to non‐carriers. In humans, constitutive STS deficiency appears associated with mood‐independent impairments in memory but not with large effects on underlying brain structure; the mediating psychobiological mechanisms might be explored further in individuals with XLI and in new mammalian models lacking STS developmentally. [ABSTRACT FROM AUTHOR]

HELIX syndrome (Hypohidrosis–Electrolyte disturbances–hypoLacrimia–Ichthyosis–Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 × 180 K microarray followed by Sanger sequencing of the CLDN10 gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene [CLDN10 (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the CLDN10 gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling. [ABSTRACT FROM AUTHOR]

The study aimed to estimate the prevalence of skin problems in children and adolescents with type 1 diabetes (T1D) using insulin pumps (IPs) and/or continuous glucose monitoring (CGM) in our center and analyze their association with various factors. As part of the international ISPAD JENIOUS-initiated SKIN-PEDIC project, we interviewed and examined patients who visited the regional pediatric diabetes center in Opole (Poland) for four weeks regarding the use of IP and/or CGM and the presence of skin problems. Body mass index (BMI) and glycemic parameters were obtained retrospectively from medical records. Among 115 individuals (45.2% girls, 83.5% IP users, 96.5% CGM users), old scars were the most common skin problem (IP users 53.1%; CGM users 66.4%), while ≥2 types of skin problems co-occurred (IP users 40.6%; CGM users 27.3%). Longer IP use was associated with a higher prevalence of skin problems (50% for IP < 1 year, 98.1%-IP 1–3 years, 100% for IP > 3 years; p < 0.001), pointing out extra attention with IP use > 1 year. No significant associations were found between skin problems and gender, age, BMI centile and glycemic parameters. Dermatological complications were common among children using IP and CGM in our center, highlighting the need for vigilant monitoring and early intervention to manage these skin-related issues effectively. [ABSTRACT FROM AUTHOR]

Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9. This single-arm, single-centre trial enrolled children (aged 1–18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF , and without bilateral cochlear implants. A single injection of AAV1-hOTOF was administered into the cochlea through the round window. The primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools. All analyses were done according to the intention-to-treat principle. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063181, and is ongoing. Between Oct 19, 2022, and June 9, 2023, we screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 × 1011 vector genomes [vg] and five received 1·5 × 1012 vg). All participants completed follow-up visits up to week 26. No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1–2 and two (4%) were grade 3 (decreased neutrophil count in one participant). Five children had hearing recovery, shown by a 40–57 dB reduction in the average auditory brainstem response (ABR) thresholds at 0·5–4·0 kHz. In the participant who received the 9 × 1011 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks. In those who received 1·5 × 1012 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks. Speech perception was improved in participants who had hearing recovery. AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9. National Natural Science Foundation of China, National Key R&D Program of China, Science and Technology Commission of Shanghai Municipality, and Shanghai Refreshgene Therapeutics. [ABSTRACT FROM AUTHOR]

Ichthyosis hystrix (Curth-Macklin ichthyosis) is an ultrarare autosomal dominant non-syndromic inherited ichthyosis belonging to the group of keratinopathic ichthyosis characterized by common histology pattern of epidermolytic hyperkeratosis. It is inherited either as an autosomal dominant or sporadic variety. We report the case of a 10-year-old male child with hyperkeratotic scales all over the body in blaschkoid pattern for 1.5 years of age with predominant involvement of flexures and relative sparing of face and scalp. There was no history of similar complaints in any family member. The case is being reported on account of rarity of the disease, that too with a very rare sporadic presentation. [ABSTRACT FROM AUTHOR]