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ABSTRACT Shwachman‐Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome characterized by the triad of exocrine pancreatic dysfunction, cytopenia, and skeletal abnormalities. We report a 5‐month‐old boy with SDS who presented with generalized ichthyosis in the neonatal period that evolved into more eczematous skin eruptions, accompanied by severe failure to thrive. This report highlights the importance of including SDS as a differential diagnosis in patients who present with early ichthyosis, failure‐to‐thrive, gastrointestinal symptoms and cytopenia. [ABSTRACT FROM AUTHOR]

Background: The Mendelian Disorders of Cornification (MeDOC) comprise a large number of disorders that present with either localised (palmoplantar keratoderma, PPK) or generalised (ichthyoses) signs. The MeDOC are highly heterogenic in terms of genetics and phenotype. Consequently, diagnostic process is challenging and before implementation of the next generation sequencing, was mostly symptomatic, not causal, which limited research on those diseases. The aim of the study was to genetically characterise a cohort of 265 Polish patients with MeDOC and to get insight into the skin lesions using transcriptome and lipid profile analyses. Results: We detected causal variants in 85% (226/265) patients. In addition to the primary gene defect, a pathogenic variant in another gene involved in MeDOC pathology was identified in 23 cases. We found 150 distinct variants in 33 genes, including 32 novel and 16 recurrent (present in > 5 alleles). In 43 alleles large rearrangements were detected, including deletions in the STS, SPINK5, CERS3 and recurrent duplication of exons 10–14 in TGM1. The RNA analysis using samples collected from 18 MeDOC patients and 22 controls identified 1377 differentially expressed genes - DEG. The gene ontology analysis revealed that 114 biological processes were upregulated in the MeDOC group, including i.e. epithelial cell differentiation, lipid metabolic process; homeostasis; regulation of water loss via skin; peptide cross-linking. The DEG between TGM1 and ALOX12B patients, showed that RNA profile is highly similar, though fatty acid profile in epidermal scrapings of those patients showed differences e.g. for the very long chain fatty acids (VLCFAs; FAs ≥ C20), the very long-chain monounsaturated fatty acids (VLC-MUFAs, FAs ≥ C20:1) and the n6 polyunsaturated fatty acids (n6 PUFAs). Conclusion: Our results show that NGS-based analysis is an effective MeDOC diagnostic tool. The Polish MeDOC patients are heterogenic, however recurrent variants are present. The novel variants and high number of TGM1 and SPINK5 copy number variations give further insight into molecular pathology of MeDOC. We show that secondary variants in MeDOC-related genes are present in a significant group of patients, which should be further investigated in the context of phenotype modifiers. Finally, we provide novel RNA and lipid data that characterise molecularly MeDOC epidermis. [ABSTRACT FROM AUTHOR]

Darier disease and Hailey-Hailey disease are rare autosomal dominant genodermatoses that negatively impact patient quality of life. In addition, they pose challenges to dermatologists who manage these diseases. There is currently no treatment that reliably induces remission for either disease, leaving patients dependent on symptom management. Oral and topical retinoids are the most commonly used therapies but have numerous side effects that often lead to discontinuation or inability to tolerate long-term treatment (Burge and Wilkinson in J Am Acad Dermatol 27:40–50, 1992). Due to the rarity of these diseases, there are no clinical trials investigating treatment options for the persistent flares patients experience. In light of this, dermatologists have tried various methods used in the management of other inflammatory disorders including photodynamic therapy (PDT). A systematic review was conducted to investigate this treatment option which yielded a total of 12 studies that had reported the use of photodynamic therapy (PDT) as a treatment option for Darier or Hailey-Hailey disease. Though results showed that PDT can induce disease remission for up to several months or years, there are many unanswered questions that need to be addressed before adopting PDT as a leading treatment option for those genodermatoses. In particular, cost, tolerability, and efficacy and safety in patients who are skin of color need to be further studied. Lastly, recommendations on treatment duration, number of sessions, photosensitizing agents, lasers, and continuation or discontinuation of topical and systemic medications need to be appraised before formal recommendations can be made. [ABSTRACT FROM AUTHOR]

ABSTRACT Dyskeratosis congenita (DC) is a rare inherited bone marrow disease that classically presents with the triad of oral leukoplakia, nail dystrophy, and reticular hyperpigmentation. It is most commonly caused by a defect in the DKC1 gene involved in telomere stability. Malignant progression of oral leukoplakia to squamous cell carcinoma (SCC) is rare in DC, especially in younger patients, and cutaneous SCC is only reported in 1.5% of cases of DC. Here we report a case of a 12‐year‐old female with a familial heterozygous RTEL1 (regulator of telomere elongation helicase 1) gene mutation associated with a severe phenotype of DC characterized by multiple cutaneous SCCs. [ABSTRACT FROM AUTHOR]

Phacomatosis pigmentokeratotica (PPK) is a RASopathy characterized by the presence of a sebaceous nevus and a papular speckled lentiginous nevus. This case report highlights the associated extracutaneous comorbidities, including life‐threatening arrhythmia, and introduces topical rapamycin as a potential therapeutic avenue for sebaceous nevus in PPK patients. [ABSTRACT FROM AUTHOR]

Genotype-phenotype associations in recessive dystrophic epidermolysis bullosa (RDEB) have been difficult to elucidate. To investigate RDEB genotype-phenotype associations and explore a functional approach to genotype classification. Clinical examination and genetic testing of RDEB subjects, including assessment of clinical disease by RDEB subtype and extent of blistering. Genotypes were evaluated according to each variant's effect on type VII collagen function per updated literature and subsequently categorized by degree of impact on VII collagen function as low-impact (splice/missense, missense/missense), medium-impact (premature termination codon [PTC]/missense, splice/splice), and high-impact (PTC/PTC, PTC/splice). Genotype-phenotype associations were investigated using Kruskal-Wallis and Fisher's exact tests, and age-adjusted regressions. Eighty-three participants were included. High-impact variants were associated with worse RDEB subtype and clinical disease, including increased prevalence of generalized blistering (55.6% for low-impact vs 72.7% medium-impact vs 90.4% high-impact variants, P =.002). In age-adjusted regressions, participants with high-impact variants had 40.8-fold greater odds of squamous cell carcinoma compared to low-impact variants (P =.02), and 5.7-fold greater odds of death compared to medium-impact variants (P =.05). Cross-sectional design. Functional genotype categories may stratify RDEB severity; high-impact variants correlated with worse clinical outcomes. Further validation in larger cohorts is needed. [ABSTRACT FROM AUTHOR]

Abstract Background The Mendelian Disorders of Cornification (MeDOC) comprise a large number of disorders that present with either localised (palmoplantar keratoderma, PPK) or generalised (ichthyoses) signs. The MeDOC are highly heterogenic in terms of genetics and phenotype. Consequently, diagnostic process is challenging and before implementation of the next generation sequencing, was mostly symptomatic, not causal, which limited research on those diseases. The aim of the study was to genetically characterise a cohort of 265 Polish patients with MeDOC and to get insight into the skin lesions using transcriptome and lipid profile analyses. Results We detected causal variants in 85% (226/265) patients. In addition to the primary gene defect, a pathogenic variant in another gene involved in MeDOC pathology was identified in 23 cases. We found 150 distinct variants in 33 genes, including 32 novel and 16 recurrent (present in > 5 alleles). In 43 alleles large rearrangements were detected, including deletions in the STS, SPINK5, CERS3 and recurrent duplication of exons 10–14 in TGM1. The RNA analysis using samples collected from 18 MeDOC patients and 22 controls identified 1377 differentially expressed genes - DEG. The gene ontology analysis revealed that 114 biological processes were upregulated in the MeDOC group, including i.e. epithelial cell differentiation, lipid metabolic process; homeostasis; regulation of water loss via skin; peptide cross-linking. The DEG between TGM1 and ALOX12B patients, showed that RNA profile is highly similar, though fatty acid profile in epidermal scrapings of those patients showed differences e.g. for the very long chain fatty acids (VLCFAs; FAs ≥ C20), the very long-chain monounsaturated fatty acids (VLC-MUFAs, FAs ≥ C20:1) and the n6 polyunsaturated fatty acids (n6 PUFAs). Conclusion Our results show that NGS-based analysis is an effective MeDOC diagnostic tool. The Polish MeDOC patients are heterogenic, however recurrent variants are present. The novel variants and high number of TGM1 and SPINK5 copy number variations give further insight into molecular pathology of MeDOC. We show that secondary variants in MeDOC-related genes are present in a significant group of patients, which should be further investigated in the context of phenotype modifiers. Finally, we provide novel RNA and lipid data that characterise molecularly MeDOC epidermis.

H syndrome is a rare autosomal recessive genodermatosis characterized by cutaneous manifestations and other systemic involvement. It presents with features like hyperpigmentation, hypertrichosis, hepatosplenomegaly, hearing loss, hallux valgus, hyperglycemia, low height, hypogonadism, and heart anomalies. Without a high index of suspicion, it is often misdiagnosed with other sclerodermatous cutaneous disorders. This case report highlights the clinical variability of H syndrome. An 8-year-old female child presented with hyperpigmented, hypertrichotic indurated patches with hyperglycemia and short stature. Histopathology showed dense lymphohistiocytic infiltrate and fibrosis in the dermis and subcutaneous tissue. The patient lacked features like heart anomalies, hearing loss, and hallux valgus, suggesting forme fruste presentation of H syndrome. An overlap between features of H syndrome and PHID syndrome is also suspected because of atypical presentation.

Porokeratoses (PK) are a group of uncommon dermatoses characterized by abnormal epidermal differentiation due to a disorder of the mevalonate metabolic pathway. Several clinical subtypes exist that can be associated with the same patient or affect different patients within a family and could, therefore, be different expressions of one disease. All PK subtypes share a common histopathologic finding, the cornoid lamella, a vertical stack of parakeratotic corneocytes embedded in an orthokeratotic horny layer. PK often affects immunosuppressed patients, in whom the course may parallel the level of immunosuppression. The pathogenesis of PK, which had long remained mysterious, has been recently unraveled after discovering pathogenic variants of genes involved in the mevalonate metabolic pathway. The disease is due to germline pathogenic variants of genes of this pathway but requires a second‐hit event to manifest; therefore, PK is considered a dominantly inherited but recessively expressed condition. The prognosis of PK is usually favorable, even though the lesions progress to keratinocyte carcinomas in 7%–16% of patients. The treatment of PK was based on physical (ablative) procedures and various (topical or systemic) treatments, whose efficacy is nevertheless inconsistent and often temporary. The discovery of the metabolic pathway involved in the pathogenesis of PK paved the way for the elaboration of new topical treatments (combination of statins and cholesterol), which are more regularly efficacious compared with older treatments, even though the management of some patients with PK may still be challenging. [ABSTRACT FROM AUTHOR]

Background: Non-melanocytic benign skin tumours encompass a diverse group of lesions, classified based on their cellular origin, such as epidermal, vascular, fibrous, neural, muscle, and adnexal tumours. Though they often reveal solitary lesions, multiple skin tumours focus on genodermatoses. Each syndrome exhibits distinct clinical characteristics and potential complications, including cutaneous and extra-cutaneous malignancies, some of which are potentially life-threatening. Diagnosing genetic syndromes is complex and requires numerous histopathological and immunohistochemistry tests due to similarities between the adnexal tumours and basal cell carcinoma upon pathology. Methods: To illustrate the clinical practice, we conducted a retrospective case study that included eleven patients with genodermatoses referred to a tertiary dermatology clinic from September 2018 to April 2024. We have also conducted a research study on available treatment modalities in this setting. Results: Five patients with excellent aesthetic results were treated using a recently approved FDA plasma device. After searching SCOPUS and PubMed database records, we assessed 96 original articles to present current knowledge regarding the dermato-surgical approach. Conclusions: Multiple skin tumours, especially on the face, may significantly affect patients' quality of life and have psychological consequences. An appropriate treatment selection tailored to the patient's needs should be provided. There is no standardised treatment for multiple benign tumours in genodermatoses, and selected methods with varying efficacy are employed. We presented the utility of a new plasma device in these settings. [ABSTRACT FROM AUTHOR]

Skin cancers are associated with a large number of genodermatoses. Existing knowledge and guidelines on the presentations of these genodermatoses focus disproportionately on White patients. Our goal is to identify notable characteristics in location, frequency, and severity of cutaneous findings along with the median age of skin cancers in skin-of-color (SOC) patients with skin-cancer-associated genodermatoses to improve diagnosis rates. We searched for genodermatoses on six databases. Each case report or case series was reviewed, including reports, published in English, containing adult patient descriptions. Duplicate manuscripts were removed using EndNote. The following case-level data were collected from the manuscripts: age, gender, patient country or region of origin, author country/continent of residence, skin cancer-related, and other key dermatologic features. 381 published articles, with a total of 578 SOC patients, met criteria for inclusion. SOC patients can present with fewer classic findings, such as a lower incidence of basal cell carcinomas (44%) in SOC Gorlin syndrome patients than palmar pits (66%) and mandibular cysts (66%). Differences between SOC populations were also noted, such as leukoplakia being more common in Asian dyskeratosis congenita patients (80%) in comparison to African dyskeratosis congenita patients (44%). SOC patients also have varying onset of skin cancer depending on the genodermatosis, from a median of 25 years of age in Rothmund-Thomson syndrome to 53 in Muir-Torre syndrome. In this review, SOC patients with genodermatoses can have varying presentations. Being cognizant of these characteristics may lead to earlier diagnosis and interventions to mitigate skin-cancer-related morbidity in SOC patients. [ABSTRACT FROM AUTHOR]

Xeroderma pigmentosum is a rare autosomal recessive genetic disorder, affecting nucleotide excision repair against ultraviolet radiation. This genodermatosis (a hereditary skin disorder) is distinguished by photosensitivity, alterations in cutaneous pigmentation, premature aging of the skin, and the typically observed onset of cutaneous and internal malignancies towards the conclusion of the first decade of life. In this article, we present a case involving a 4-year-old girl from North India who was born to non-consanguineous parents and developed an extensive fungating growth on her face. Subsequent diagnosis revealed the presence of squamous cell carcinoma, resulting in significant facial disfigurement. While xeroderma pigmentosum is a recognized condition, its occurrence in India, particularly in the northern region, is relatively rare. This report also underscores a noteworthy observation—the emergence of a cutaneous malignancy at such a tender age. [ABSTRACT FROM AUTHOR]

Of patients with a Noonan syndrome phenotype, only about 1% are found to be related to pathological variants in CBL, also known as Noonan syndrome‐like disorder (NSLD). We present a case of a 4‐year‐old boy diagnosed with NSLD, presenting with multiple melanocytic nevi and superficial neurofibromas. A literature review identified common cutaneous findings of NSLD, for example, café‐au‐lait macules (22%), juvenile xanthogranuloma (16%), and thin hair (10%). As there are no documented cases of neurofibromas associated with NSLD, and only a single report of multiple melanocytic nevi, inclusion of these features in the phenotype may be warranted and mitigate the necessity for future biopsies in other children. [ABSTRACT FROM AUTHOR]

PLACK syndrome (OMIM 616295) is a rare genodermatosis associated with peeling skin, leukonychia, acral punctate keratosis, cheilitis, and knuckle pads and is caused by loss‐of‐function mutations in the CAST gene, which encodes calpastatin, a calcium‐dependent protease. This case report highlights a case of PLACK syndrome presenting with the unique findings of striate hyperkeratosis on the palms as well as life‐threatening cardiomyopathy. We review why CAST mutations might impact cardiac function and raise awareness of the potential association between PLACK syndrome and cardiac manifestations. [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]

The article discusses non-pachyonychia congenita conditions found in the International Pachyonychia Congenita Research Registry. Pachyonychia congenita is a rare disorder with specific clinical features, and genetic testing is crucial for an accurate diagnosis. The registry has identified other rare skin disorders with similar phenotypes, such as Clouston syndrome, Olmsted syndrome, and striate palmoplantar keratoderma, caused by different gene variants. Genetic testing is emphasized for accurate diagnosis and appropriate clinical management of these conditions. [Extracted from the article]

ABSTRACT We report on a 13‐year‐old boy diagnosed with hypohidrotic ectodermal dysplasia (HED) due to a pathogenic variant in ectodysplasin A (EDA). He exhibited multiple whitish, millimetric papules clustered on the nasal ala, forehead, temporal, and zygomatic arch areas. Histological examination revealed numerous hyperplastic sebaceous lobules within the upper dermis. The occurrence of sebaceous papules in this distribution among HED patients has rarely been reported. An association with the blockage of the Wnt/β‐catenin pathway due to EDA malfunction has been speculated. [ABSTRACT FROM AUTHOR]

This article presents a case study of an 8-year-old male with multiple café-au-lait macules, axillary freckling, and hypopigmented macules. The patient's sister also had similar features and a history of T-cell lymphoblastic lymphoma. Although the patient initially met the clinical criteria for neurofibromatosis type 1 (NF1), further assessment suggested a diagnosis of constitutional mismatch repair deficiency (CMMRD). Genetic testing confirmed a homozygous pathogenic variant in the PMS2 gene. CMMRD is a rare autosomal recessive syndrome associated with an increased risk of cancer, and early diagnosis is crucial for initiating appropriate surveillance and management. [Extracted from the article]

Background: Epidermolysis bullosa (EB) is a clinically-heterogeneous genodermatosis with severe manifestations in the skin and other organs. The significant burden this condition places on patients justifies the development of gene therapeutic strategies targeting the genetic cause of the disease.Methods: Emerging RNA and DNA editing tools have shown remarkable advances in efficiency and safety. Applicable both in ex vivo- and in vivo settings, these gene therapeutics based on gene replacement or editing are either at the pre-clinical or clinical stage.Results: The recent landmark FDA approvals for gene editing based on CRISPR/Cas9, along with the first FDA-approved redosable in vivo gene replacement therapy for EB, will invigorate ongoing research efforts, increasing the likelihood of achieving local cure via CRISPR-based technologies in the near future.Conclusions: This review discusses the status quo of current gene therapeutics that act at the level of RNA or DNA, all with the common aim of improving the quality of life for EB patients.

Collodion baby is usually a manifestation of autosomal recessive congenital ichthyosis, a heterogeneous group of congenital hyperkeratotic genodermatoses with highly variable severity and genetic background. Herein, we report a case of self-improving collodion ichthyosis, a rare subtype of autosomal recessive congenital ichthyosis, characterized by an almost-complete spontaneous resolution of symptoms.

Epidermolysis bullosa pruriginosa is an extremely rare form of dystrophic epidermolysis bullosa. Its cause is the underlying mutation, most often in the COL7A1 gene. Based upon a specific type of mutation in a patient (missense, non-sense, frameshift, splice-site mutations), a distinct, specific phenotype can be observed. This study presents a case series of three family members from the Pomerania region in Poland, with a novel missense mutation of p.Val2402Gly/-c.7205T>G in exon 94 of the COL7A1 gene. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa simplex (EBS) is a dermatological condition marked by skin fragility and blister formation resulting from separation within the basal layer of the epidermis, which can be attributed to various genetic etiologies. This study presents three pathogenic de novo variants in young children, with clinical manifestations appearing as early as the neonatal period. The variants contribute to the EBS phenotype through two distinct mechanisms: direct keratin abnormalities due to pathogenic variants in the Krt14 gene, and indirect effects via pathogenic mutation in the KLHL24 gene, which interfere with the natural proteasome-mediated degradation pathway of KRT14. We report one severe case of EBS with mottled pigmentation arising from the Met119Thr pathogenic variant in KRT14, another case involving a pathogenic KLHL24 Met1Val variant, and a third case featuring the hot spot mutation Arg125His in KRT14, all manifesting within the first few weeks of life. This research underscores the complexity of genetic influences in EBS and highlights the importance of early genetic screening for accurate diagnosis and management. [ABSTRACT FROM AUTHOR]

This article discusses a rare autoinflammatory syndrome called STING-associated vasculopathy with onset in infancy (SAVI). The article presents a case study of a 7-year-old Chinese girl with SAVI who had a somatic mosaic mutation in the TMEM137 gene. The girl exhibited various clinical manifestations, including cutaneous vasculitis, thrombocytopenia, hypothyroidism, and other complications. The article highlights the importance of genetic mutations in the TMEM173 gene, which lead to the activation of the interferon and NF-jb pathways. The authors also mention the potential use of JAK inhibitors for treating SAVI. [Extracted from the article]

The Indian Association of Dermatologists, Venereologists, and Leprologists (IADVL) has established the I-CuReD registry in India to collect data on rare skin disorders. The registry has recorded 323 patients with genodermatoses, with epidermolysis bullosa and congenital ichthyosis being the most common diseases. The article provides detailed information on the demographics, symptoms, and diagnostic methods used for these patients. The study found a lower number of cases compared to other countries and highlights the need for further research in this area. The authors acknowledge the limitations of their study and hope for more comprehensive studies in the future. [Extracted from the article]

This study underscores the significance of identifying the clinical manifestations of pachyonychia congenita (PC) and emphasizes the patterns of genetic inheritance. A 12‐month‐old boy presented with a “white hairy tongue” and, following a comprehensive evaluation, was diagnosed with PC. His father exhibited similar symptoms. Genetic testing revealed a KRT16 pathogenic variant (c.616 T > G) in both the patient and his father, marking it as a novel variant in the PC literature. This case contributes to a broader understanding of PC's genetic diversity and its clinical presentations. [ABSTRACT FROM AUTHOR]

Congenital ichthyoses sometimes present with severe skin symptoms that significantly affect the patient's quality of life (QOL). Symptomatic treatments are the mainstay therapies, and their efficacy is limited and inadequate. To assess the disease severity and QOL in patients with congenital ichthyoses, and to investigate the effectiveness of current treatments. We conducted a questionnaire-based Japan-wide epidemiological survey of patients with congenital ichthyosis who received medical care from 1 January 2016–31 December 2020. Effectiveness of past and current treatments was assessed. The outcomes were the physician's assessment, disease severity assessed using the clinical ichthyosis score (CIS), and the disease burden estimated using the Dermatology Life Quality Index (DLQI), the Children's Dermatology Life Quality Index (CDLQI), and the Infants' Dermatitis Quality of Life Index. One hundred patients with 14 ichthyosis subtypes from 47 institutes were included in the final analysis. The CDLQI score showed a positive correlation with CIS (rs = 0.59, p = 0.004), while the DLQI score showed no significant correlation (rs = 0.13, p = 0.33). All existing medications were effective for many patients. Etretinate improved QOL and reduced CIS, but side effects including bone growth retardation were reported. Decreased treatment willingness was observed in patients with very low and very high CIS. QOL scores were found to correlate with CIS in children, but not in adults. Considering the adverse events, it is speculated that etretinate is not indicated for children with mild cases. Petrolatum was the most commonly used medication, even in patients who were reluctant to receive treatment. • 100 patients with congenital ichthyosis were included in the present study. • QOL scores were found to correlate with CIS in children, but not in adults. • The true effectiveness of etretinate treatment was demonstrated. • Surprisingly few patients discontinued etretinate due to side effects. • The majority of patients used petrolatum irrespective of treatment willingness. [ABSTRACT FROM AUTHOR]

Background: Acitretin, a synthetic vitamin A derivative, is the most studied and widely used oral retinoid for ichthyoses. Its major disadvantage is the need for contraceptive measures during 3 years after discontinuation. An alternative is needed for women of childbearing age. With alitretinoin, another retinoid, pregnancy is considered safe 1 month after discontinuation. Objectives: The aim of this study was to provide evidence for alitretinoin as an alternative for acitretin for ichthyosis in women of childbearing age. Our experience is shared in a case series combined with an overview of the current literature. Methods: Nine women of childbearing age (19–31 years, median 21) with different subtypes of ichthyosis (autosomal recessive congenital ichthyosis, (superficial) epidermolytic ichthyosis, erythrokeratoderma variabilis, and epidermolytic epidermal nevi, a mosaic form of epidermolytic ichthyosis) were included and treated with 30 mg alitretinoin during 2–28 months. Severity was measured by Ichthyosis Area Severity Index (IASI) and Investigator Global Assessment (IGA). A literature search in Pubmed using the Mesh terms "alitretinoin," "skin diseases, genetic" and "ichthyosis" was performed. Results: Significant reduction in the mean scores of IGA, IASI-erythema, IASI-scaling, and IASI-total was seen. Seven patients are still being treated, 1 patient stopped to become pregnant, 1 patient discontinued due to financial reasons. Observed side effects were reversible headache (n = 6), asteatotic eczema (n = 1), "not feeling well" temporarily (n = 1), and easier blistering of the feet (n = 1). The literature search resulted in six case reports and case series about alitretinoin in ichthyosis and ichthyosis syndromes with in total 29 patients. The vast majority of articles (21/29) reported significant improvement or even complete remission of skin symptoms. However, validated outcome measures to support these results were lacking. Side effects (n = 16) were relatively mild, except for benign intracranial hypertension (n = 1) and autoimmune hypothyroidism (n = 1). Conclusion: Our study shows, with validated outcome measures, that alitretinoin is effective to mitigate the symptoms of ichthyosis in women of childbearing age and a suitable alternative to acitretin. [ABSTRACT FROM AUTHOR]

Genodermatoses are diseases with significant psychosocial impact despite being relatively rare conditions, with a reported incidence that varies between 1:6000 and 1:500,000 [1] and is continually increasing, most likely due to the development of more effective diagnostic methods. Severity of the clinical expression of the genetic defects responsible for the occurrence of genodermatoses varies widely, with some cases taking the form of serious diseases that cause significant alteration of patients' quality of life, as well as that of their families, and also reduce the patients' life expectancy. Given the fact that genodermatoses are chronic, incurable diseases that are frequently associated with incapacitating disabilities and even with malignant degeneration potential, their management requires collaboration among members of a multidisciplinary team and a complex therapeutic regimen, which also demands considerable resources. Therefore, taking into account all these considerations, genodermatoses represent important public health issues. In the current paper we present the results of a prospective and retrospective study conducted between 2013 and 2023 on a number of 253 newly diagnosed patients with various clinical forms of genodermatoses, admitted to Dermatology departments in Bucharest. [ABSTRACT FROM AUTHOR]

Introduction: Epidermolysis bullosa (EB) represents a group of rare disorders, genetically determined, characterized by skin fragility, blister formation and erosions due to minimal trauma. Depending on the ultrastructural level of skin cleavage, above or below the basement membrane, epidermolysis bullosa can be classified into four major types: simplex, junctional, dystrophic and Kindler Syndrome. In the junctional form of EB, the cleavage level is at the dermo-epidermal junction and the targeted proteins are laminin, type XVII collagen and integrins. The dystrophic form of EB is characterized by cleavage in the dermal layer, collagen VII being the targeted protein. In Kindler EB, multiple levels of cleavage have been described. The mutated gene is FERMT1. Another classification of this disease refers to phenotypic aspects such as extracutaneous lesions, severity, and distribution. The management of epidermolysis bullosa includes supportive wound treatments as well as nutritional support. Case report: We present a case of epidermolysis bullosa presented at birth, in a newborn with no family history of bullous skin conditions. The clinical presentation revealed extensive denuded areas and significant skin fragility as well as mucous and nail involvement. Prenatal diagnosis is very hard to achieve due to increased genetic heterogeneity of the disease. The short-term results were good. The importance of prenatal testing and possibilities of diagnosis are reviewed in this article. Conclusions: EB is a devastating disease. The presented case had a favorable evolution, with good short-term results. Significant morbidity can result from secondary infections of blisters and complications of the extracutaneous manifestations.

Abstract is missing (Quiz)

Severe junctional epidermolysis bullosa is a rare genetic, postpartum lethal skin disease, predominantly caused by nonsense/premature termination codon (PTC) sequence variants in LAMB3 gene. LAMB3 encodes LAMB3, the β subunit of epidermal–dermal skin anchor laminin 332. Most translational reads of a PTC mRNA deliver truncated, nonfunctional proteins, whereas an endogenous PTC readthrough mechanism produces full-length protein at minimal and insufficient levels. Conventional translational readthrough-inducing drugs amplify endogenous PTC readthrough; however, translational readthrough-inducing drugs are either proteotoxic or nonselective. Ribosome editing is a more selective and less toxic strategy. This technique identified ribosomal protein L35/uL29 (ie, RpL35) and RpL35-ligands repurposable drugs artesunate and atazanavir as molecular tools to increase production levels of full-length LAMB3. To evaluate ligand activity in living cells, we monitored artesunate and atazanavir treatment by dual luciferase reporter assays. Production levels of full-length LAMB3 increased up to 200% upon artesunate treatment, up to 150% upon atazanavir treatment, and up to 170% upon combinatorial treatment of RpL35 ligands at reduced drug dosage, with an unrelated PTC reporter being nonresponsive. Proof of bioactivity of RpL35 ligands in selective increase of full-length LAMB3 provides the basis for an alternative, targeted therapeutic route to replenish LAMB3 in severe junctional epidermolysis bullosa.

Pruritus is one of the most debilitating symptoms for patients with epidermolysis bullosa (EB). This study aimed to assess the burden of itch and to address its dimensions across patients with EB. Forty-six patients with EB were recruited from the Saudi EB registry to participate. All participants completed the Leuven Itch Scale. The sample included 5 patients with EB simplex (EBS), 3 with junctional EB (JEB), 34 with dystrophic EB (DEB), and 4 patients had unknown type. Overall, 97.8% patients reported itch. In patients with itch, 73.3% reported that it was often or always present, longer than 2h Itch episodes was reported by JEB (66.7%) and recessive DEB (3.2%). Itch, in all its dimensions, was worst in patients with JEB and DEB than EBS. Itch occurred mostly in a hot environment (80%), when sweating (71.1%), in healing wounds (40%), and during dressing change (35.6%) whereas cold environment resulted in itch in only (2.2%). The burden of pruritus increased with increasing age. This study highlights a challenging area in EB care with a need for specific treatments. [ABSTRACT FROM AUTHOR]

Background: Epidermolysis bullosa (EB) features skin and mucosal fragility due to pathogenic variants in genes encoding components of the cutaneous basement membrane. Based on the level of separation within the dermal‐epidermal junction, EB is sub‐classified into four major types including EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler EB (KEB) with 16 EB‐associated genes reported to date. Methods: We ascertained a cohort of 151 EB patients of various Middle Eastern ethnic backgrounds. Results: The cohort was comprised of EBS (64%, 97/151), DEB (21%, 31/151), JEB (12%, 18/151), and KEB (3%, 5/151). KRT14 and KRT5 variants were most common among EBS patients with 43% (42/97) and 46% (45/97) of EBS patients carrying mutations in either of these two genes, respectively. Truncal involvement was more common in KRT14‐associated EBS as compared to EBS due to KRT5 mutations (p <.05). Mutations in COL17A1 and laminin 332‐encoding genes were identified in 55% (10/18) and 45% (8/18) of JEB patients. Scarring alopecia, caries, and EB nevi were most common among JEB patients carrying COL17A1 mutations as compared to laminin 332‐associated JEB (p <.05). Abnormal nails were evident in most DEB and JEB patients while poikiloderma was exclusively observed in KEB (p <.001). Conclusions: EB patients of Middle Eastern origin were found to feature specific phenotype–genotype correlations of relevance to the diagnosis and genetic counseling of patients in this region. [ABSTRACT FROM AUTHOR]

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Xeroderma pigmentosum (XP), a heterogeneous genodermatoses, has a variable clinical spectrum ranging from mild freckling and photosensitivity to severe skeletal and neurological abnormalities and cutaneous malignancies. Herein, we present the case of a 4‐year‐old boy with XP group G who presented with a pellagroid rash. [ABSTRACT FROM AUTHOR]

A 3‐week‐old baby with hydrops fetalis, acute respiratory failure, and shock of unknown etiology developed a diffuse, pustular rash with worsening inflammatory markers and respiratory status despite antimicrobials. Whole exome sequencing revealed a de novo, frameshift mutation in the SAM9DL gene, leading to the diagnosis of SAMD9L‐associated autoinflammatory disease. [ABSTRACT FROM AUTHOR]

Over the past decade, Next-Generation Sequencing (NGS) has advanced our understanding, diagnosis, and management of several areas within dermatology. NGS has emerged as a powerful tool for diagnosing genetic diseases of the skin, improving upon traditional PCR-based techniques limited by significant genetic heterogeneity associated with these disorders. Epidermolysis bullosa and ichthyosis are two of the most extensively studied genetic diseases of the skin, with a well-characterized spectrum of genetic changes occurring in these conditions. NGS has also played a critical role in expanding the mutational landscape of cutaneous squamous cell carcinoma, enhancing our understanding of its molecular pathogenesis. Similarly, genetic testing has greatly benefited melanoma diagnosis and treatment, primarily due to the high prevalence of BRAF hot spot mutations and other well-characterized genetic alterations. Additionally, NGS provides a valuable tool for measuring tumor mutational burden, which can aid in management of melanoma. Lastly, NGS demonstrates promise in improving the sensitivity of diagnosing cutaneous T-cell lymphoma. This article provides a comprehensive summary of NGS applications in the diagnosis and management of genodermatoses, cutaneous squamous cell carcinoma, melanoma, and cutaneous T-cell lymphoma, highlighting the impact of NGS on the field of dermatology.

Introduction: Epidermolysis bullosa (EB) represents a group of rare disorders, genetically determined, characterized by skin fragility, blister formation and erosions due to minimal trauma. Depending on the ultrastructural level of skin cleavage, above or below the basement membrane, epidermolysis bullosa can be classified into four major types: simplex, junctional, dystrophic and Kindler Syndrome. In the junctional form of EB, the cleavage level is at the dermo-epidermal junction and the targeted proteins are laminin, type XVII collagen and integrins. The dystrophic form of EB is characterized by cleavage in the dermal layer, collagen VII being the targeted protein. In Kindler EB, multiple levels of cleavage have been described. The mutated gene is FERMT1. Another classification of this disease refers to phenotypic aspects such as extracutaneous lesions, severity, and distribution. The management of epidermolysis bullosa includes supportive wound treatments as well as nutritional support. Case report: We present a case of epidermolysis bullosa presented at birth, in a newborn with no family history of bullous skin conditions. The clinical presentation revealed extensive denuded areas and significant skin fragility as well as mucous and nail involvement. Prenatal diagnosis is very hard to achieve due to increased genetic heterogeneity of the disease. The short-term results were good. The importance of prenatal testing and possibilities of diagnosis are reviewed in this article. Conclusions: EB is a devastating disease. The presented case had a favorable evolution, with good short-term results. Significant morbidity can result from secondary infections of blisters and complications of the extracutaneous manifestations. [ABSTRACT FROM AUTHOR]