Lamellar Ichthyosis Research Articles

Epidermolytic Hyperkeratosis Type 1 with a New Heterozygous Mutation in KRT1 Gene: A Case Report

Background: Epidermolytic hyperkeratosis (EHK) formerly known as bullous ichthyosiform erythroderma, is a rare autosomal dominant inheritance condition with a prevalence ranging from 1:200,000 to 1:300,000. The underlying etiology of which is a mutation in the genes responsible for keratin proteins synthesis, primarily in KRT1 and KRT10 genes, cataloged under OMIM number 113800. Clinicopathological presentations include blistering in the neonatal period followed by ichthyotic hyperkeratosis in childhood and adolescence, characterized by the hallmark features of generalized dry skin, scaling, hyperkeratosis, and frequently associated with erythroderma. EHK may present with or without palmoplantar keratoderma involvement, depending on the keratin gene variant. Case report: A 24-year-old male of Arab descent was born with diffuse skin hyperkeratotic plates featuring erythematous fissures, covering his entire body, resembling a collodion baby. His birth was full-term via cesarean section without complications, although he later developed developmental dysplasia of the hip. By the time he started primary school, he began experiencing severe thickening of the skin around his joints, reducing flexibility and leading to contractures and significant disfigurement. He is undergoing treatment with acitretin. Genetic testing using Next-Generation Sequencing (NGS) was performed to identify the responsible gene, revealing a novel heterozygous variant in the KRT1 gene (OMIM 139350), while no variant was detected in the KRT10 gene. Conclusion: EHK type 1 manifests with a new heterozygous variant in the KRT1 gene. This rare disorder, associated with variant in genes related to keratin production such as KRT1 and KRT10, results in distinctive skin features present from birth, as well as joint problems and fungal foot infections. Genetic testing has confirmed the presence of a variant in the KRT1 gene.

From Phenotype to Genotype: A Collodion Baby Case Linked to CERS3 Mutation

The term “Collodion baby” is used to describe a newborn appearing with a tight, shiny, and parchment like film covering the entire body. The collodion baby is not a distinct condition but a presentation shared by various disorders. This phenotype may evolve into a range of abnormalities, such as lamellar ichthyosis, Harlequin ichthyosis, non-bullous congenital ichthyosiform erythroderma, and intermediate phenotypes. We report a case of a collodion baby who was found to have a rare mutation in CERS3 gene. Despite the potential for numerous complications arising from impaired skin barrier function, the patient experienced a remarkable recovery following meticulous management and was subsequently discharged home.

Alopecia patterns and trichoscopic findings in patients with autosomal recessive congenital ichthyosis.

Autosomal recessive congenital ichthyosis (ARCI) is a rare genodermatosis categorized among nonsyndromic ichthyoses. While ARCI patients often manifest hair abnormalities, their impact on the quality of life remains underreported in the literature. This study aims to comprehensively characterize the clinical and trichoscopic findings of alopecia in ARCI patients. A prospective study spanning from January 2019 to December 2021 (3 years) was conducted at the Dermatology Department of Habib Thameur Hospital, Tunis, Tunisia. Clinical and trichoscopic examinations were performed on the hair of the participants, with molecular studies conducted on 15 patients. The study included 30 patients, predominantly female (male/female = 0.58), with a mean age of 20 years. Twenty-eight patients were born from consanguineous marriages. Lamellar ichthyosis was observed in 22 cases, while congenital ichthyosiform erythroderma and bathing suit ichthyosis were each present in 4 cases. The ARCI severity score, assessed using the Visual Index For Ichthyosis Severity scale, had a mean value of 15 (4-28). Alopecia emerged as a prominent finding in 11 patients, presenting as hairline recession (13%), multiple patchy alopecia (27%), and alopecia of the eyebrows (13%). Trichoscopic findings included interfollicular and perifollicular scaling, perifollicular lamellar hyperkeratosis, peripilar casts, interfollicular erythema, loss of hair openings, predominance of single hair follicles, broken hair, vellus hair, anisotrichosis, pili torti, dystrophic hair, and comma hair. Several trichoscopic findings showed statistically significant associations with the severity of ARCI. In our study, we only included 30 patients due to the rarity of this genodermatosis. Contrary to previous perceptions, alopecia is a notable finding in ARCI, particularly in patients with a severe form. This study provides a detailed characterization of alopecia in ARCI, shedding light on its prevalence and associated trichoscopic features, thereby enhancing our understanding of this dermatological condition.

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.

Vitamin D Supplementation in Congenital Ichthyosis: A Case Series.

Ichthyosis is a group of genetic keratinization disorders characterized by excessive scaling that is associated with hyperproliferative epidermis and/or cellular retention. Whereas normal outer epidermis thickness is 25 μm, it can be 10-fold greater in patients with ichthyosis. As a result, photoactivation of 7-dehydrocholesterol is impaired, causing systemic vitamin D deficiency.In this case series, 25 patients with congenital ichthyosis with vitamin D deficiency (<10 ng/mL) were supplemented with 60,000 IU of vitamin D3 for 10 days followed by daily allowance of 400 to 600 IU of vitamin D3 and 40 mg/kg per day of elemental calcium. The authors assessed improvement in cutaneous scaling and body and tested patients' blood and urine samples at day 1, day 10, 1 month, and 3 months. They also documented patients' Dermatology Life Quality Index score before and after treatment.All patients had normal vitamin D levels; supplementation was discontinued for two patients who reached a level of 100 ng/mL within 10 days. Subjective improvement of symptoms (dryness of the skin, allergic rhinitis, tightness of the skin, and scaling) was observed by both the provider and the patients. There was remarkable improvement in symptoms of severe ichthyosis such as lamellar ichthyosis (tightness of the skin and scaling). Marked improvement in Dermatology Life Quality Index score was also noted.This case series demonstrated remarkable symptomatic relief with vitamin D supplementation in patients with congenital ichthyosis; however, additional research should be conducted with larger sample sizes to support these findings.

A cellular disease model toward gene therapy of TGM1-dependent lamellar ichthyosis

Lamellar Ichthyosis (LI) is a chronic disease, mostly caused by mutations in TGM1 gene, marked by impaired skin barrier formation. No definitive therapies are available and current treatments aim at symptomatic relief. LI mouse models often fail to faithfully replicate the clinical and histopathological features of human skin conditions. To develop advanced therapeutic approaches, as combined ex vivo cell and gene therapy, we established a human cellular model of LI by efficient CRISPR-Cas9-mediated gene ablation of the TGM1 gene in human primary clonogenic keratinocytes. Gene edited cells showed complete absence of Transglutaminase-1 (TG1) expression and recapitulated a hyperkeratotic phenotype with most of the molecular hallmarks of LI in vitro. Using a SINγ-RV vector expressing transgenic TGM1 under the control of its own promoter, we tested an ex vivo gene therapy approach and validate the model of LI as a platform for pre-clinical evaluation studies. Gene-corrected TGM1-null keratinocytes displayed proper TG1 expression, enzymatic activity and cornified envelopes formation, hence restored proper epidermal architecture. Single cell multiomic analysis demonstrated proviral integrations in holoclone-forming epidermal stem cells, which are crucial to epidermal regeneration. This study serves as a proof-of-concept for assessing the potential of this therapeutic approach in treating TGM1 dependent LI.

Collodion Baby And Cholestasis: A Rare Case Report

Collodion baby with cholestasis is an uncommon condition. The term "collodion baby" refers to newborns with thick skin covering their entire body. Neonatal cholestasis is a form of conjugated cholestasis hyperbilirubinemia caused by reduced bile flow. The condition causes persistent jaundice (over two weeks) and elevated conjugated bilirubin. Genetic abnormalities or gene mutations have been reported in neonatal ichthyosis syndrome with cholestasis. A case report of a collodion baby, a rare congenital condition characterized by a parchment-like membrane covering the entire body, was brought to Dr. Soetomo General Academic Hospital. Prolonged jaundice was one of the other findings. A skin biopsy found characteristics consistent with the diagnosis of collodion in a newborn. The paediatric team managed this case, which was treated in collaboration with a dermatologist. This case showed that newborn collodion syndrome required skin care, cholestasis screening, and jaundice management from birth.

Advancements in Ichthyosis Treatment in Pediatric Patients: Evaluating the Impact of Immune System Inhibitors Targeting TNF-alpha, IL-17A, IL-4, and IL-12

Lamellar, X-linked recessive, and Vulgaris ichthyosis represent rare genetic variants distinguished by abundant dry surface scales. The etiology of childhood ichthyosis involves a combination of acquired and inherited factors. Children with Ichthyosis have a Th17-dominant immune profile, similar to psoriasis, with a correlation between ichthyosis severity, erythema, Trans Epidermal Water Loss (TEWL), and immunological markers. In order to examine the safety and effectiveness of immune system inhibitors that target TNF-alpha, IL-17A, IL-4, and IL-12 in the treatment of pediatric Ichthyosis, a retrospective research study was conducted on 30 pediatric patients aged 6-12 years at tertiary care pediatric dermatology hospitals in UAE, for a time duration of 5 months. IL-17-A is a key cytokine of Ichthyosis, and its specific suppression is considered necessary in contrast to other cytokines. Consequently, the choice of treatment was dictated by elements unique to the condition and the intensity of symptoms, focusing on using Secukinumab as an IL-17-A inhibitor. The findings showed that, following five months of treatment, patients receiving secukinumab showed positive outcomes, with their ichthyosis area severity index score declining by 45 to 50%. Additionally, the proinflammatory rate of cytokines was significantly lower in this group of patients compared to the placebo-treated control group. The safety and Efficacy of Secukinumab compared to Ixekizumab and Brodalumab vs placebo were examined using t-tests, with statistical significance determined at P&lt; 0.05. The present research study concludes that Secukinumab effectively enhances skin texture and reduces scaling severity in Ichthyosis, suggesting clinical relevance. The findings underscore Secukinumab’s potential as a beneficial agent for various ichthyosis types, such as lamellar, X-linked, and vulgaris. The study’s comparison with placebo and other IL-17A inhibitors like Ixekizumab and Brodalumab provides valuable insights into Secukinumab’s Efficacy and potential clinical uses.

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.

Assessing the Application of Large Language Models in Generating Dermatologic Patient Education Materials According to Reading Level: Qualitative Study.

Dermatologic patient education materials (PEMs) are often written above the national average seventh- to eighth-grade reading level. ChatGPT-3.5, GPT-4, DermGPT, and DocsGPT are large language models (LLMs) that are responsive to user prompts. Our project assesses their use in generating dermatologic PEMs at specified reading levels. This study aims to assess the ability of select LLMs to generate PEMs for common and rare dermatologic conditions at unspecified and specified reading levels. Further, the study aims to assess the preservation of meaning across such LLM-generated PEMs, as assessed by dermatology resident trainees. The Flesch-Kincaid reading level (FKRL) of current American Academy of Dermatology PEMs was evaluated for 4 common (atopic dermatitis, acne vulgaris, psoriasis, and herpes zoster) and 4 rare (epidermolysis bullosa, bullous pemphigoid, lamellar ichthyosis, and lichen planus) dermatologic conditions. We prompted ChatGPT-3.5, GPT-4, DermGPT, and DocsGPT to "Create a patient education handout about [condition] at a [FKRL]" to iteratively generate 10 PEMs per condition at unspecified fifth- and seventh-grade FKRLs, evaluated with Microsoft Word readability statistics. The preservation of meaning across LLMs was assessed by 2 dermatology resident trainees. The current American Academy of Dermatology PEMs had an average (SD) FKRL of 9.35 (1.26) and 9.50 (2.3) for common and rare diseases, respectively. For common diseases, the FKRLs of LLM-produced PEMs ranged between 9.8 and 11.21 (unspecified prompt), between 4.22 and 7.43 (fifth-grade prompt), and between 5.98 and 7.28 (seventh-grade prompt). For rare diseases, the FKRLs of LLM-produced PEMs ranged between 9.85 and 11.45 (unspecified prompt), between 4.22 and 7.43 (fifth-grade prompt), and between 5.98 and 7.28 (seventh-grade prompt). At the fifth-grade reading level, GPT-4 was better at producing PEMs for both common and rare conditions than ChatGPT-3.5 (P=.001 and P=.01, respectively), DermGPT (P<.001 and P=.03, respectively), and DocsGPT (P<.001 and P=.02, respectively). At the seventh-grade reading level, no significant difference was found between ChatGPT-3.5, GPT-4, DocsGPT, or DermGPT in producing PEMs for common conditions (all P>.05); however, for rare conditions, ChatGPT-3.5 and DocsGPT outperformed GPT-4 (P=.003 and P<.001, respectively). The preservation of meaning analysis revealed that for common conditions, DermGPT ranked the highest for overall ease of reading, patient understandability, and accuracy (14.75/15, 98%); for rare conditions, handouts generated by GPT-4 ranked the highest (14.5/15, 97%). GPT-4 appeared to outperform ChatGPT-3.5, DocsGPT, and DermGPT at the fifth-grade FKRL for both common and rare conditions, although both ChatGPT-3.5 and DocsGPT performed better than GPT-4 at the seventh-grade FKRL for rare conditions. LLM-produced PEMs may reliably meet seventh-grade FKRLs for select common and rare dermatologic conditions and are easy to read, understandable for patients, and mostly accurate. LLMs may play a role in enhancing health literacy and disseminating accessible, understandable PEMs in dermatology.

Compound heterozygous ABCA12 variants identified in a Chinese patient with congenital ichthyosiform erythroderma: Advancing genotype-phenotype correlations and literature review.

Ichthyosis is a common keratotic skin disease with high clinical, etiological and genetic heterogeneity. There are four types of non-syndromic hereditary ichthyoses, among which autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of recessive Mendelian disorders. ARCI present with different phenotypes and ABCA12 pathogenic variants have been shown to cause complex ARCI phenotypes, including harlequin ichthyosis (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). A sporadic male patient, clinically diagnosed with CIE, was enrolled in this study. Exome sequencing was combined with Sanger sequencing to confirm the diagnosis and identify the pathogenic variants. In silico predictions were made using multiple software programs, and the identified variants were interpreted using the ACMG guidelines. A review of all literature reported ABCA12 variants was performed to explore genotype-phenotype correlations. Compound heterozygous ABCA12 variants [c.5381+1G>A and c.5485G>C (p.Asp1829His)] (NM_173076) were identified. The two variants were not detected in the public database. c.5381+1G>A is predicted to affect ABCA12 mRNA splicing and Asp1829 is highly conserved among various species. In silico analysis suggested that these two variants were responsible for the phenotype of the patient. Genotype-phenotype correlation analysis showed that biallelic truncation variants and/or exon/amino acid deletions in ABCA12 are the most common causes of HI. Biallelic missense variants are most common in LI and CIE. The compound heterozygous ABCA12 variants caused the CIE phenotype observed in the patient. The spectrum of ABCA12 pathogenic variants were broaden. Genotype-phenotype correlation analysis provided detailed evidence which can be used in future prenatal diagnosis and can inform the need for genetic counselling for patients with ABCA12-related ARCIs.

Collodion Baby Progressing to Camisa Syndrome: Case Report and Review of Literature in Asian Population

Palmoplantar keratoderma (PPK) is a broad entity comprising wide range of hereditary and acquired disorders. Herein, we present a case of 18-year-old female who presented with complaints of palmoplantar thickening since birth and progressive constriction bands around digits for 3 years. On examination, diffuse transgradient honeycomb type of PPK was present. Fibrous constriction bands (pseudoainhum) were present circumferentially around the distal interphalangeal joint of fifth finger and metatarsophalangeal joint of fifth toe bilaterally. Punch biopsy from palms revealed hyperkeratotic, stratified squamous epithelium with vacuolar degeneration and prominent keratohyaline granules. Audiogram was normal. On the basis of history, clinical examination and investigations, a diagnosis of Camisa syndrome was made and the patient was started on oral retinoids. We also discussed case findings of Camisa Syndrome reported in Asian population.

Genetics of lamellar ichthyosis

Ichthyosis is a dermatological condition that causes the skin in a wide range of integumentary regions of the body to become dry, rough, and scaly. Ichthyosis affect 5–10/100 000 people worldwide. Lamellar ichthyosis (LI) is part of autosomal recessive congenital ichthyosis and is a significant type of inherited ichthyosis in no-syndromic form. Patients with LI are susceptible to depression and low quality of life. TGM1 gene is the primary gene affected in LI. Clinical manifestations of LI are large scales on lower extremities; hence, the management of LI would consist of hydration, keratolytic, and oral retinoid. Genetic counseling are also recommended for patients with LI and their families. This review provides a brief discussion on the genetics of LI.

Cross-Sectional Study on Autosomal Recessive Congenital Ichthyoses: Association of Genotype with Disease Severity, Phenotypic, and Ultrastructural Features in 74 Italian Patients

Background: Autosomal recessive congenital ichthyoses (ARCIs) are a clinically heterogeneous group of keratinization disorders characterized by generalized skin scaling due to mutations in at least 12 genes. The aim of our study was to assess disease severity, phenotypic, and ultrastructural features and to evaluate their association with genetic findings in ARCI patients. Methods: Clinical signs and symptoms, and disease severity were scored in a single-center series of patients with a genetic diagnosis of ARCI. Skin ultrastructural findings were reviewed. Results: Seventy-four consecutive patients (mean age 11.0 years, range 0.1–48.8) affected with lamellar ichthyosis (50/74, 67.5%), congenital ichthyosiform erythroderma (18/74, 24.3%), harlequin ichthyosis (two/74, 2.7%), and other minor ARCI subtypes (four/74, 5.4%) were enrolled. Mutated genes were as follows: TGM1 in 18/74 (24.3%) patients, ALOX12B in 18/74 (24.3%), CYP4F22 in 12/74 (16.2%), ABCA12 in nine/74 (12.2%), ALOXE3 in seven/74 (9.5%), NIPAL4 in seven/74 (9.5%), and CERS3, PNPLA1, and SDR9C7 in 1 patient each (1.4%). Twenty-five previously undescribed mutations in the different ARCI causative genes, as well as two microduplications in TGM1, and two microdeletions in CYP4F22 and NIPAL4 were identified. The mean ichthyosis severity score in TGM1- and ABCA12-mutated patients was significantly higher than in all other mutated genes, while the lowest score was observed in CYP4F22-mutated patients. Alopecia, ectropion, and eclabium were significantly associated with TGM1 and ABCA12 mutations, and large, thick, and brownish scales with TGM1 mutations. Among specific phenotypic features, psoriasis-like lesions as well as a trunk reticulate scale pattern and striated keratoderma were present in NIPAL4-mutated patients. Ultrastructural data available for 56 patients showed a 100% specificity of cholesterol clefts for TGM1-mutated cases and revealed abnormal lamellar bodies in SDR9C7 and CERS3 patients. Conclusion: Our study expands the phenotypic and genetic characterization of ARCI by the description of statistically significant associations between disease severity, specific clinical signs, and different mutated genes. Finally, we highlighted the presence of psoriasis-like lesions in NIPAL4-ARCI patients as a novel phenotypic feature with diagnostic and possible therapeutic implications.

Updated mutational spectrum and genotype-phenotype correlations in ichthyosis patients with ABCA12 pathogenic variants.

Autosomal recessive congenital ichthyoses (ARCI) is a genetically heterogeneous condition that can be caused by pathogenic variants in at least 12 genes, including ABCA12. ARCI mainly consists of congenital ichthyosiform erythroderma (CIE), lamellar ichthyosis (LI) and harlequin ichthyosis (HI). The objective was to determine previously unreported pathogenic variants in ABCA12 and to update genotype-phenotype correlations for patients with pathogenic ABCA12 variants. Pathogenic variants in ABCA12 were detected using Sanger sequencing or a combination of Sanger sequencing and whole-exome sequencing. To verify the pathogenicity of a previously unreported large deletion and intron variant, cDNA analysis was performed using total RNA extracted from hair roots. Genetic analyses were performed on the patients with CIE, LI, HI and non-congenital ichthyosis with unusual phenotypes (NIUP), and 11 previously unreported ABCA12 variants were identified. Sequencing of cDNA confirmed the aberrant splicing of the variant ABCA12 in the patients with the previously unreported large deletion and intron variant. Our findings expand the phenotype spectrum of ichthyosis patients with ABCA12 pathogenic variants. The present missense variants in ABCA12 are considered to be heterogenous in pathogenicity, and they lead to varying disease severities in patients with ARCI and non-congenital ichthyosis with unusual phenotypes (NIUP).

Clinical Spectrum of Congenital Ichthyosis in Pediatric Age Group from a Tertiary Care Center in India

Objective: Ichthyosis is a disorder of cornification, which can be acquired or inherited, and encompasses various forms of generalized scaling and superficial roughness of the skin secondary to impaired skin barrier. It can be often associated with systemic manifestations. There is a paucity of Indian studies assessing the clinical and demographic profile of children with inherited ichthyosis. Hence, we conducted this study with the primary objective of assessing the clinical and epidemiological profile of children with congenital ichthyosis (CI). Materials and Methods: The study was conducted over 1 year. All children aged up to 18 years of age, with the clinical diagnosis of CI, were evaluated for epidemiological profile and clinical features. Results: A total of 32 children with CI presented with a mean age of 6 ± 4.81 years. The most common phenotype was ichthyosis vulgaris, seen in 13 (40.6%) children, while X-linked recessive ichthyosis was present in 6 (18.75%) children. Epidermolytic ichthyosis (EI) was also seen in 6 (18.75%) children, out of which 5 were diagnosed with generalized EI and 1 was diagnosed with superficial EI. Lamellar ichthyosis was seen in 4 (12.5%) children. Sjogren–Larsson syndrome (SLS), harlequin ichthyosis, and Netherton syndrome were present in 1 (3.1%) case each. Various extracutaneous abnormalities detected were ectropion (9.3%), lagophthalmos (3.1%), and refractive error with stye (3.1%) on ophthalmological evaluation, gross development delay (8.75%), and neurological involvement in the form of spastic quadriplegia (one patient with SLS). Conclusions: CI comprises various skin diseases and can range from mild to very severe presentation with systemic involvement. Identification of the phenotypic expression of ichthyosis is a prerequisite for making prognostic predictions, therapeutic decisions, and offering genetic counseling.

Autosomal Dominant Lamellar Ichthyosis Due to a Missense Mutation in the Gene NKPD1

The identification of monogenic causes for cornification disorders has enhanced our understanding of epidermal differentiation and skin barrier function. Autosomal dominant lamellar ichthyosis (ADLI) is a rare condition, and ASPRV1 was the only gene linked to ADLI to date. We identified a heterozygous variant (ENST00000686631.1:c.1372G>T, p.(Val458Phe)) in the NKPD1 gene in seven individuals from a four-generation German pedigree with generalized lamellar ichthyosis by whole exome sequencing. Segregation analysis confirmed its presence in affected individuals, resulting in a LOD score of 3.31. NKPD1 encodes the NTPase KAP Family P-Loop Domain-Containing Protein 1, implicated in the plasma membrane, its role in human disease is as yet unknown. Skin histology showed moderate acanthosis and compact orthohyperkeratosis, and the ultrastructure differed clearly from that in ASPRV1-ADLI. While NKPD1 mRNA expression increased during keratinocyte differentiation, stratum corneum ceramides exhibited no significant changes. However, affected individuals showed an elevated ratio of protein-bound ceramides to omega-esterified ceramides. This highlights NKPD1's role in ADLI, impacting ceramide metabolism and skin lipid barrier formation, as demonstrated through functional characterization.

Genetic inheritance in tandem: Non-syndromic autosomal recessive congenital ichthyosis with beta-thalassaemia: A rare coincidence

Ichthyosis belongs to the group of Mendelian disorders of cornification. Congenital ichthyosis is inherited as an autosomal recessive trait, so it is also known as autosomal recessive congenital ichthyosis (ARCI). ARCI is classified into two types: syndromic and non-syndromic ARCI. Non-syndromic ARCIs include lamellar ichthyosis, congenital ichthyosiform erythroderma and Harlequin ichthyosis. Syndromic-ARCI is associated with multisystemic involvement, which includes Netherton syndrome, Chanarin-Dorfman disease and others. Other systemic diseases associated with ichthyosis include Gaucher disease type II and hypothyroidism. Chanarin-Dorfman and Gaucher disease-II are additionally associated with hepatosplenomegaly (HSM) and anaemia. We describe a child of congenital ichthyosis with HSM and anaemia thought to be syndromic-ARCI, but diagnosed for beta-thalassaemia (b-thal) concurrently. An infant presented with peeling skin along with absent sweating since birth and recent onset paleness of the body. Examination revealed Ichthyosis (Lamellar-variant), severe pallor and HSM, raising the possibility of Chanarin-Dorfman syndrome and Gaucher’s disease. The investigation revealed an Erlenmeyer flask deformity of the knee, but no Gaucher’s cells were found in the bone marrow. In the absence of lipid vacuoles leaden leukocytes (Jordan’s anomaly), Chanarin-Dorfman disease was also ruled out. Haemoglobin (Hb) high-performance liquid chromatography revealed β-thal major, and both parents were traits, giving us the diagnosis, which was further confirmed by the next-generation gene sequencing for clinical exomes. This report was to highlight non-syndromic ARCI involving the CYP4F22 gene variant, which is a rare finding, and the association of such ichthyosis with β-thal major was an unexpected result. Genetic counselling was provided to the parents in light of the autosomal recessive nature of both diseases. Genes of congenital ichthyosis and β-thal were unrelated, but simultaneous expressions of two autosomal-recessive diseases together are it merely by chance or a new entity.

Newborns with Collodion Skin Disorders

Collodion Baby is a descriptive term for newborns with the entire surface of the body wrapped in a rigid yellowish membrane that resembles solid and translucent parchment paper. A rare disorder that often occurs in preterm babies with low birth weight. Collodion babies can have defects in protein and fat metabolism due to genetic mutations. Management with emollients, fluid and electrolyte balance and overcoming infection. Case Report : Reported newborn came to the emergency room of Soeselo Hospital referral from Puskesmas with Collodion Baby and low birth weight. Yellowish skin is obtained throughout the body such as translucent thick parchment, fissures with some erosion and ecropions in both eyes. The patient is placed in an incubator with a temperature of 30-32o C, emollient therapy, topical antibiotics on fissures and erosions, prophylactic antibiotics and antibiotic creams for ectropion. Discussion : Collodion baby is a condition at risk of serious complications including: risk of infection, hypernatremic dehydration, fluid and electrolyte imbalances and temperature instability caused by epidermal lipid disorders and protein homeostasis, resulting in increased transepidermal water loss (TEWL) caused by mutations in the transglutaminase 1-TGM1, ALOXE3 or ALOX12B, ABCA12, HIPAL4/ichthyin, ABHD5 genes responsible for epidermal homeostasis. Conclusion: Collodion Baby is a disorder with severe corneal damage. The importance of proper and comprehensive management with the aim of minimizing complications can reduce morbidity and mortality.

Assessment Of The Status And Challenges Of The Linkage Between Universities And Industries In Ethiopia: The Case Of Two Universities And Six Industries

The primary objective is to report and document the case of a collodion baby, a rare congenital condition, emphasizing the importance of early and appropriate therapeutic intervention. By presenting this infrequent incidence, the aim is to contribute to the existing medical knowledge regarding the clinical symptoms and complications associated with collodion baby syndrome. Specifically, the goal is to highlight the significance of prompt and adequate management in minimizing potential complications due to skin barrier disruption. This involves implementing a treatment approach focused on eliminating scaling and reducing xerosis without causing excessive irritation to the delicate skin of the affected newborn. Furthermore, the report seeks to enhance clinical awareness among healthcare professionals, providing valuable insights into the symptoms that should be monitored closely and the multidisciplinary care required. Collaboration between pediatricians, dermatologists, otorhinolaryngologists, ophthalmologists, plastic surgeons, and physiotherapists is crucial for comprehensive care, addressing immediate concerns, and ensuring long-term survival and well-being. In summary, the objective is twofold: first, to contribute to the medical literature by documenting a rare collodion baby syndrome, and second, to underscore the importance of early intervention and multidisciplinary care in managing this congenital condition and minimizing associated complications.