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).

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.

Identification and In Silico Analysis of a Homozygous Nonsense Variant in TGM1 Gene Segregating with Congenital Ichthyosis in a Consanguineous Family.

Background and Objectives: Lamellar ichthyosis is a rare skin disease characterized by large, dark brown plate-like scales on the entire body surface with minimum or no erythema. This phenotype is frequently associated with a mutation in the TGM1 gene, encoding the enzyme transglutaminase 1 which plays a catalytic role in the formation of the cornified cell envelop. The present study aimed to carry out clinical and genetic characterization of the autosomal recessive lamellar ichthyosis family from Balochistan. Materials and Methods: A consanguineous family with lamellar ichthyosis was enrolled from Balochistan, Pakistan. PCR amplification of all the exons and splice site junctions of the TGM1 gene followed by Sanger sequencing was performed on the genomic DNA. The identified variant was checked by In silico prediction tools to evaluate the effect of the variant on protein. Results: Sanger sequencing identified a homozygous nonsense variant c.131G >A (p.Trp44*) in the TGM1 gene that segregated in the autosomal recessive mode of inheritance in the family. The identified variant results in premature termination of transcribed mRNA and is predicted to cause a truncated or absent translation product transglutaminase-1 (TGase-1) accompanied by loss of catalytic activity, causing a severe clinical phenotype of lamellar ichthyosis in the patients. Conclusions: Here, we report a consanguineous lamellar ichthyosis family with a homozygous nonsense variant in the TGM1 gene. The variant is predicted as pathogenic by different In silico prediction tools.

Ophthalmic findings in patients with autosomal recessive lamellar ichthyosis due to TGM1 mutations in an isolated population.

PURPOSE: To describe the ocular clinical characteristics of a group of Mexican patients with lamellar ichthyosis (LI) arising from TGM1 pathogenic variants. METHODS: Ophthalmological exploration, pedigree analysis and genetic screening were performed in patients with an established clinical diagnosis of lamellar ichthyosis from families located in a small community in the Southeast of Mexico. RESULTS: Nine patients with LI in five families were identified. There were six affected females. All patients (9/9) demonstrated eye lid abnormalities with eight patients showing lid margin abnormalities. Madarosis was present in only three individuals and corneal scarring was documented in two. All nine individuals carried biallelic TGM1 variants, either homozygously or as compound heterozygous. CONCLUSION: Ocular anomalies are common in individuals with TGM1-related LI. The occurrence of a variety of private or rare mutations hampers the identification of a genotype-phenotype correlation for ocular anomalies in this disorder.

Genotype of autosomal recessive congenital ichthyosis from a tertiary care center in India.

BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) refers to non-syndromic ichthyosis caused by mutations in one of the 13 identified genes. There are limited data on the genotype of ARCI and its phenotypic correlation from India. OBJECTIVES: The aim of this study was to characterize the genotype of ARCI among patients from the Indian subcontinent. METHODS: Twenty-eight patients clinically diagnosed as ARCI were recruited prospectively from September 2017 to June 2019 (21 months). DNA was extracted from peripheral blood and analyzed for the 13 described ARCI genes-TGM1, ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, and CASP14 by next-generation sequencing using an in-house panel. The variants identified were confirmed by Sanger sequencing and compared with known pathogenic variants to establish pathogenicity. We also attempted to correlate the phenotype with the genotype. RESULTS: Among the 28 patients recruited (M = 17, F = 11), we identified phenotypes of congenital ichthyosiform erythroderma in 12 (42.9%), 8 with lamellar ichthyosis (28.6%), 5 with intermediate phenotype (17.9%), and 3 with bathing suit ichthyosis (10.7%). Pathogenic and likely pathogenic variants were identified in 22 (78.6%) patients, involving 7 out of the 13 known ARCI genes while 6 (21.4%) did not have pathogenic variants. These included TGM1 mutation in 6 (21.4%), ALOX12B and ALOXE3 in 4 (14.3%) each, NIPAL4 and PNPLA1 in 3 (10.7%) each, and ABCA12 and CERS3 in 1 (3.6%) patient each. Previously unknown pathogenic variants were found in 59.1 % of patients. CONCLUSIONS: Our patients with ARCI were found to have genotypes as previously described in other populations.

Current Strategies for the Gene Therapy of Autosomal Recessive Congenital Ichthyosis and Other Types of Inherited Ichthyosis.

Mutations in genes such as transglutaminase-1 (TGM1), which are responsible for the formation and normal functioning of a lipid barrier, lead to the development of autosomal recessive congenital ichthyosis (ARCI). ARCIs are characterized by varying degrees of hyperkeratosis and the presence of scales on the body surface since birth. The quality of life of patients is often significantly affected, and in order to alleviate the manifestations of the disease, symptomatic therapy with moisturizers, keratolytics, retinoids and other cosmetic substances is often used to improve the condition of the patients' skin. Graft transplantation is commonly used to correct defects of the eye. However, these approaches offer symptomatic treatment that does not restore the lost protein function or provide a long-term skin barrier. Gene and cell therapies are evolving as promising therapy for ARCIs that can correct the functional activity of altered proteins. However, these approaches are still at an early stage of development. This review discusses current studies of gene and cell therapy approaches for various types of ichthyosis and their further prospects for patient treatment.

Congenital lamellar ichthyosis complicated with erosive pseudo pustulosis: A rare clincal entity. About a case and review of the literature.

INTRODUCTION: Lamellar ichthyosis is a rare congenital disorder that can be encountered by plastic surgeon in a daily practice. Its clinical diagnosis makes it an significant pathology to identify and to know how to treat. MATERIAL AND METHODS: We report the case of a patient suffering from lamellar ichthyosis complicated by erosive pseudo pustulosis of the scalp. Our treatment protocol with two intra-lesional delayed-corticoids (Kenacort ®) injections three months apart showed significant clinical improvement of the lesions. DISCUSSION: Congenital lamellar ichthyosis regroups various clinical presentations. Most of the therapeutic strategies described in the literature involve local and systemic treatments, weighing on patients and leading to modest results. Surgical treatment or hyaluronic injections have also been reported but they raise problematics regarding morbidity and efficiency. CONCLUSION: Our therapeutic strategy by two Kenacort ® injections three months apart is simple, reproductible and has shown efficiency in the treatment of our patient suffering from congenital lamellar ichthyosis complicated with erosive pseudo pustulosis of the scalp.

Molecular epidemiology of non-syndromic autosomal recessive congenital ichthyosis in a Middle-Eastern population.

Autosomal recessive congenital ichthyosis (ARCI) is a rare and heterogeneous skin cornification disorder presenting with generalized scaling and varying degrees of erythema. Clinical manifestations range from lamellar ichthyosis (LI), congenital ichthyosiform erythroderma (CIE) through the most severe form of ARCI, Harlequin ichthyosis (HI). We used homozygosity mapping, whole-exome and direct sequencing to delineate the relative distribution of pathogenic variants as well as identify genotype-phenotype correlations in a cohort of 62 Middle Eastern families with ARCI of various ethnic backgrounds. Pathogenic variants were identified in most ARCI-associated genes including TGM1 (21%), CYP4F22 (18%), ALOX12B (14%), ABCA12 (10%), ALOXE3 (6%), NIPAL4 (5%), PNPLA1 (3%), LIPN (2%) and SDR9C7 (2%). In 19% of cases, no mutation was identified. Our cohort revealed a higher prevalence of CYP4F22 and ABCA12 pathogenic variants and a lower prevalence of TGM1 and NIPAL4 variants, as compared to data obtained in other regions of the world. Most variants (89%) in ALOX12B were associated with CIE and were the most common cause of ARCI among patients of Muslim origin (26%). Palmoplantar keratoderma associated with fissures was exclusively a result of pathogenic variants in TGM1. To our knowledge, this is the largest cohort study of ARCI in the Middle-Eastern population reported to date. Our data demonstrate the importance of population-tailored mutation screening strategies and shed light upon specific genotype-phenotype correlations.

Increased risk of depression and impairment in quality of life in patients with lamellar ichthyosis.

Lamellar ichthyosis (LI) is a genetic skin disorder characterized by dark brown scales, palmoplantar hyperkeratosis, pain, and itching. LI severity could have implications in psychological aspects, causing depression and impairment in the quality of life (QoL) of patients. In this study, we used the Congenital Ichthyosis Severity Index, the Depression Beck Inventory-II (DBI-II), and the Dermatologic Life Quality Index (DLQI) to assess severity, level of depression, and impairment in QoL in a group of patients with LI. We observed that the majority of the patients presented a high severity level concerning the presence of scales (57.7%), while for erythema and alopecia, the severity was less 80% of the analyzed patients presented depression, while only 20.8% of individuals of the control group presented it (P < .001, OR = 15.2). While for QoL, only 4.3% of the patients did not exhibit any impairment. Finally, the increase in the score obtained in DBI-II was correlated with the DLQI score (rs = 0.663, P = .0014). Our results suggest that patients with LI have an increased risk of suffering depression and impairment in their QoL; thus, the management of their disease should be performed from a multidisciplinary perspective to improve the global aspects of their lives.

The Burden of Autosomal Recessive Congenital Ichthyoses on Patients and their Families: An Italian Multicentre Study.

Autosomal recessive congenital ichthyoses (ARCI) are characterized by generalized skin scaling, hyperkeratosis, erythroderma, and disabling features affecting the skin (palmoplantar keratoderma, fissures, pain, itch), eyes, ears, and joints. Disease severity and chronicity, patient disfigurement, and time and costs required for care impose a major burden on quality of life. This multicentre cross-sectional study investigated the impact of ARCI on quality of life of patients and families, using the Dermatology Life Quality Index (DLQI), the Children DLQI (CDLQI) and Family Burden of Ichthyosis (FBI) questionnaires. Disease severity was assessed by a dermatologist. A total of 94 patients were recruited, of whom 52 (55.3%) children. Mean age was 20.1 (median 13.5) years. The mean CDLQI/DLQI score was 7.8, and 21 patients scored >10, indicating a major impairment in quality of life: symptoms, feelings and treatment problems were the most affected domains of quality of life. FBI showed a major repercussion on psychological factors and work. The results of this study highlight the impact of ARCI on specific aspects of patient and family life, underlining the need for psychological support.

Novel progressive acrodysostosis-like skeletal dysplasia, cerebellar atrophy, and ichthyosis.

Acrodysostosis refers to a rare heterogeneous group of bone dysplasias that share skeletal features, hormone resistance, and intellectual disability. Two genes have been associated with acrodysostosis with or without hormone resistance (PRKAR1A and PDE4D). Severe intellectual disability has been reported with acrodysostosis but brain malformations and ichthyosis have not been reported in these syndromes. Here we describe a female patient with acrodysostosis, intellectual disability, cerebellar hypoplasia, and lamellar ichthyosis. The patient has an evolving distinctive facial phenotype and childhood onset ataxia. X-rays showed generalized osteopenia, shortening of middle and distal phalanges, and abnormal distal epiphysis of the ulna and radius. Brain magnetic resonance imaging showed cerebellar atrophy without other brainstem abnormalities. Genetic workup included nondiagnostic chromosomal microarray and skeletal dysplasia molecular panels. These clinical findings are different from any recognized form of acrodysostosis syndrome. Whole exome sequencing did not identify rare or predicted pathogenic variants in genes associated with known acrodysostosis, lamellar ichthyosis, and other overlapping disorders. A broader search for rare alleles absent in healthy population databases and controls identified two heterozygous truncating alleles in FBNL7 and PPM1M genes, and one missense allele in the NPEPPS gene. Identification of additional patients is required to delineate the mechanism of this unique disorder.

Bathing suit ichthyosis: Two Burmese siblings and a review of the literature.

Bathing suit ichthyosis (BSI) is a subtype of autosomal recessive congenital ichthyosis (ARCI) characterized by the development of large platelike scales mainly limited to the trunk. It is caused by temperature sensitive variants in transglutaminase 1, encoded by the gene TGM1. We describe a rare case of intrafamilial variation in phenotypic expressivity in two Burmese siblings with BSI that demonstrates the heterogeneity of the disorder within the same family and even in the same individual across time. We also present a concise review of the genotypic spectrum of BSI from 54 cases reported in the literature as evidence that both environmental and additional genetic factors can significantly alter the clinical phenotype.

Ichthyosis molecular fingerprinting shows profound TH17 skewing and a unique barrier genomic signature.

BACKGROUND: Ichthyoses are a group of rare skin disorders lacking effective treatments. Although genetic mutations are progressively delineated, comprehensive molecular phenotyping of ichthyotic skin could suggest much-needed pathogenesis-based therapy. OBJECTIVE: We sought to profile the molecular fingerprint of the most common orphan ichthyoses. METHODS: Gene, protein, and serum studies were performed on skin and blood samples from 29 patients (congenital ichthyosiform erythroderma, n = 9; lamellar ichthyosis, n = 8; epidermolytic ichthyosis, n = 8; and Netherton syndrome, n = 4), as well as age-matched healthy control subjects (n = 14), patients with psoriasis (n = 30), and patients with atopic dermatitis (AD; n = 16). RESULTS: Using criteria of a fold change of greater than 2 and a false discovery rate of less than 0.05, 132 differentially expressed genes were shared commonly among all ichthyoses, including many IL-17 and TNF-α-coregulated genes, which are considered hallmarks of psoriasis (defensin beta 4A, kynureninase, and vanin 3). Although striking upregulation of TH17 pathway genes (IL17F and IL36B/G) resembling that seen in patients with psoriasis was common to all patients with ichthyoses in a severity-related manner, patients with Netherton syndrome showed the greatest T-cell activation (inducible costimulator [ICOS]) and a broader immune phenotype with TH1/IFN-γ, OASL, and TH2/IL-4 receptor/IL-5 skewing, although less than seen in patients with AD (all P < .05). Ichthyoses lacked the epidermal differentiation and tight junction alterations of patients with AD (loricrin, filaggrin, and claudin 1) but showed characteristic alterations in lipid metabolism genes (ELOVL fatty acid elongase 3 and galanin), with parallel reductions in extracellular lipids and corneocyte compaction in all ichthyoses except epidermolytic ichthyosis, suggesting phenotypic variations. Transepidermal water loss, a functional barrier measure, significantly correlated with IL-17-regulated gene expression (IL17F and IL36A/IL36B/IL36G). CONCLUSION: Similar to patients with AD and psoriasis, in whom cytokine dysregulation and barrier impairment orchestrate disease phenotypes, psoriasis-like immune dysregulation and lipid alterations characterize the ichthyoses. These data support the testing of IL-17/IL-36-targeted therapeutics for patients with ichthyosis similar to those used in patients with psoriasis.

Results of a nationwide epidemiologic survey of autosomal recessive congenital ichthyosis and ichthyosis syndromes in Japan.

BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) and ichthyosis syndrome (IS) are rare genetic skin disorders. OBJECTIVE: To estimate the number of patients with ARCI and IS in Japan and clarify the clinicoepidemiologic features of these diseases. METHODS: We performed a nationwide survey of patients treated for ARCI or IS during January 2005-December 2009. We developed diagnostic criteria and conducted a primary survey in a stratified random sample of Japanese hospitals to quantify the number of outpatients and inpatients with ARCI or IS. We performed a secondary survey of clinicoepidemiologic features in positive cases. RESULTS: The estimated number of patients receiving treatment for ARCI and IS during 2005-2009 was 220 (95% confidence interval [CI] 180-260). The estimated disease distribution was as follows: 95 (95% CI 80-110) patients with nonbullous congenital ichthyosiform erythroderma, 30 (95% CI 20-40) with lamellar ichthyosis, 15 (95% CI 10-20) with harlequin ichthyosis, and 85 (95% CI 50-120) with IS. LIMITATIONS: Patients with a mild case of the disease might not have visited a dermatology department, potentially causing underestimation of affected patients. CONCLUSION: We report the estimated number of patients with ARCI and IS in Japan and sex differences in the age distribution.

Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications.

Enzymes in the cytochrome P450 4 (CYP4) family are involved in the metabolism of fatty acids, xenobiotics, therapeutic drugs, and signaling molecules, including eicosanoids, leukotrienes, and prostanoids. As CYP4 enzymes play a role in the maintenance of fatty acids and fatty-acid-derived bioactive molecules within a normal range, they have been implicated in various biological functions, including inflammation, skin barrier, eye function, cardiovascular health, and cancer. Numerous studies have indicated that genetic variants of CYP4 genes cause inter-individual variations in metabolism and disease susceptibility. Genetic variants of CYP4A11, 4F2 genes are associated with cardiovascular diseases. Mutations of CYP4B1, CYP4Z1, and other CYP4 genes that generate 20-HETE are a potential risk for cancer. CYP4V2 gene variants are associated with ocular disease, while those of CYP4F22 are linked to skin disease and CYP4F3B is associated with the inflammatory response. The present study comprehensively collected research to provide an updated view of the molecular functionality of CYP4 genes and their associations with human diseases. Functional analysis of CYP4 genes with clinical implications is necessary to understand inter-individual variations in disease susceptibility and for the development of alternative treatment strategies.

Mutation update for CYP4F22 variants associated with autosomal recessive congenital ichthyosis.

Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of rare disorders of keratinization characterized by generalized abnormal scaling of the skin. Ten genes are currently known to be associated with ARCI: TGM1, ALOXE3, ALOX12B, NIPAL4 (ICHTHYIN), ABCA12, CYP4F22, PNPLA1, CERS3, SDR9C7, and SULT2B1. Over a period of 22 years, we have studied a large patient cohort from 770 families with a clinical diagnosis of ARCI. Since the first report that mutations in the gene CYP4F22 are causative for ARCI in 2006, we have identified 54 families with pathogenic mutations in CYP4F22 including 23 previously unreported mutations. In this report, we provide an up-to-date overview of all published and novel CYP4F22 mutations and point out possible mutation hot spots. We discuss the molecular and clinical findings, the genotype-phenotype correlations and consequences on genetic testing.

Severe ectropion in lamellar ichthyosis managed medically with oral acitretin.

Congenital ectropion is commonly associated with lamellar ichthyosis. Severe eyelid ectropion may cause corneal exposure, keratopathy, and permanent corneal scarring. We report a neonate with severe, bilateral, congenital ectropion and eclabium managed using oral retinoids. Both corneas were protected with topical antibiotics and lubricating eyedrops and eye ointments. At 12-month follow-up, the child was doing well, with no ectropion or corneal opacity.

An IL-17-dominant immune profile is shared across the major orphan forms of ichthyosis.

BACKGROUND: The ichthyoses are rare genetic disorders associated with generalized scaling, erythema, and epidermal barrier impairment. Pathogenesis-based therapy is largely lacking because the underlying molecular basis is poorly understood. OBJECTIVE: We sought to characterize molecularly cutaneous inflammation and its correlation with clinical and barrier characteristics. METHODS: We analyzed biopsy specimens from 21 genotyped patients with ichthyosis (congenital ichthyosiform erythroderma, n = 6; lamellar ichthyosis, n = 7; epidermolytic ichthyosis, n = 5; and Netherton syndrome, n = 3) using immunohistochemistry and RT-PCR and compared them with specimens from healthy control subjects, patients with atopic dermatitis (AD), and patients with psoriasis. Clinical measures included the Ichthyosis Area Severity Index (IASI), which integrates erythema (IASI-E) and scaling (IASI-S); transepidermal water loss; and pruritus. RESULTS: Ichthyosis samples showed increased epidermal hyperplasia (increased thickness and keratin 16 expression) and T-cell and dendritic cell infiltrates. Increases of general inflammatory (IL-2), innate (IL-1ß), and some TH1/interferon (IFN-γ) markers in patients with ichthyosis were comparable with those in patients with psoriasis or AD. TNF-α levels in patients with ichthyosis were increased only in those with Netherton syndrome but were much lower than in patients with psoriasis and those with AD. Expression of TH2 cytokines (IL-13 and IL-31) was similar to that seen in control subjects. The striking induction of IL-17-related genes or markers synergistically induced by IL-17 and TNF-α (IL-17A/C, IL-19, CXCL1, PI3, CCL20, and IL36G; P < .05) in patients with ichthyosis was similar to that seen in patients with psoriasis. IASI and IASI-E scores strongly correlated with IL-17A (r = 0.74, P < .001) and IL-17/TNF-synergistic/additive gene expression. These markers also significantly correlated with transepidermal water loss, suggesting a link between the barrier defect and inflammation in patients with ichthyosis. CONCLUSION: Our data associate a shared TH17/IL-23 immune fingerprint with the major orphan forms of ichthyosis and raise the possibility of IL-17-targeting strategies.

Concomitant extraspinal hyperostosis and osteoporosis in a patient with congenital ichthyosis.

Ichthyosiform dermatosis is a term referred to a group of disorders that have as their basis a disorder of keratinization (1). These conditions which are present at birth result in a generalized dry, scaly skin without any inflammation. There are several types of ichthyosis based on their clinical presentation and mode of inheritance. The most common types are: ichthyosis vulgaris, X-linked recessive ichthyosis, epidermolytic hyperkeratosis (bullous), lamellar ichthyosis and non-bullous ichthyosiform erythroderma. Lamellar ichthyosis, which is inherited in an autosomal recessive pattern, shows genetic heterogeneity with the most severe type being due to mutations in the transglutaminase-1 gene. This condition presents with skin changes at birth and cases are referred to as collodion babies. Initially, the stratum corneum is smooth and appears as though it is covered with cellophane. This layer is discarded a few days after birth, leaving a generalized inflamed and scaly appearance. The skin is tight at this stage and may cause ectropion, and difficulties in feeding and temperature regulation. Lamellar ichthyosis is characterized by plate-like scales that last for life and can significantly impact the patient's quality of life (2). We report here a case of multiple extraspinal hyperostoses concomitant with marked osteoporosis and vitamin D deficiency in a patient taking acitretin for 20 years due to severe congenital lamellar ichthyosis.