RESUMO
Resumen Las ictiosis congénitas autosómicas recesivas (ICAR) son poco frecuentes a nivel mundial con una incidencia de 1:300,000 nacimientos, se caracterizan por trastornos de la queratinización, entre sus variantes engloban las formas no sindrómicas de ictiosis, como la ictiosis laminar (IL), la eritrodermiaictiosiforme congénita (EIC) y actualmente se incluyen la ictiosis arlequín, el bebé colodión autorresolutivo, el bebé colodión autorresolutivoacral y la ictiosis en traje de baño. Desde el punto de vista genético son heterogéneas, originadas por una mutación en el gen de la transglutaminasa 1 y se las haasociado a TGM1, ALOXE3, ALOX12B, NIPAL4, CYP4F22 y ABCA12. Clínicamente, la ictiosis se caracteriza principalmente por piel gruesa, escamas laminares adherentes con hendiduras profundas. En este trabajo pretende revisar los conocimientos actuales en el campo de las ICAR, incluyendo aspectos clínicos, histológicos, ultraestructurales, genético-moleculares, tratamiento,y también su manejo clínico.
Abstract The autosomal recessive congenital ichthyosis (ARCI) is a rare worldwide condition with an incidence of (1: 300,000 births), characterized by disorders of keratinization, among its variants encompass the non-syndromic forms of ichthyosis, such as laminar ichthyosis (IL) , congenital ichthyosiform erythroderma (EIC) and currently include harlequin ichthyosis, self-healing colodion baby, acral self-healing colodion baby and ichthyosis in swimsuits. From a genetic point of view, they're heterogeneous, originated by a mutation in the gene of transglutaminase 1 and associated with TGM1, ALOXE3, ALOX12B, NIPAL4, CYP4F22 and ABCA12. Clinically, ichthyosis is mainly characterized by thick skin, adherent lamellar scales with deep clefts. The aim of this work is to review the current knowledge in the field of ICAR, including clinical, histological, ultrastructural, genetic-molecular and therapeutic aspects as well as its clinical management.
Assuntos
Humanos , Feminino , Pré-Escolar , Transglutaminases/biossíntese , Ictiose Lamelar/patologia , Ictiose Lamelar/tratamento farmacológico , Ictiose/epidemiologia , Ictiose Lamelar/diagnósticoRESUMO
An unusually high frequency of the lamellar ichthyosis TGM1 mutation, c.1187G > A, has been observed in the Ecuadorian province of Manabí. Recently, the same mutation has been detected in a Galician patient (Northwest of Spain). By analyzing patterns of genetic variation around this mutation in Ecuadorian patients and population matched controls, we were able to estimate the age of c.1187G > A and the time to their most recent common ancestor (TMRCA) of c.1187G > A Ecuadorian carriers. While the estimated mutation age is 41 generations ago (~1,025 years ago [ya]), the TMRCA of Ecuadorian c.1187G > A carrier haplotypes dates to just 17 generations (~425 ya). Probabilistic-based inferences of local ancestry allowed us to infer a most likely European origin of a few (16% to 30%) Ecuadorian haplotypes carrying this mutation. In addition, inferences on demographic historical changes based on c.1187G > A Ecuadorian carrier haplotypes estimated an exponential population growth starting ~20 generations, compatible with a recent founder effect occurring in Manabí. Two main hypotheses can be considered for the origin of c.1187G > A: (i) the mutation could have arisen in Spain >1,000 ya (being Galicia the possible homeland) and then carried to Ecuador by Spaniards in colonial times ~400 ya, and (ii) two independent mutational events originated this mutation in Ecuador and Galicia. The geographic and cultural characteristics of Manabí could have favored a founder effect that explains the high prevalence of TGM1 c.1187G > A in this region.
Assuntos
Ictiose Lamelar/patologia , Transglutaminases/genética , Equador , Genótipo , Haplótipos , Humanos , Ictiose Lamelar/genética , Polimorfismo de Nucleotídeo Único , Análise de Componente Principal , Sequências de Repetição em Tandem/genéticaRESUMO
BACKGROUND: Autosomal recessive congenital ichthyoses (ARCI) have been associated with different phenotypes including: harlequin ichthyosis (HI), congenital ichthyosiform erythroderma (CIE), and lamellar ichthyosis (LI). While pathogenic variants in all ARCI genes are associated with LI and CIE phenotypes, the unique gene associated with HI is ABCA12. In HI, the most severe ARCI form, pathogenic variants in both ABCA12 gene alleles usually have a severe impact on protein function. The presence of at least one non-truncating variant frequently causes a less severe congenital ichthyosis phenotype (LI and CIE). METHODS: We report the case of a 4-year-old Ecuadorian boy with a severe skin disease. Genetic diagnosis was performed by NGS. In silico predictions were performed using Alamut software v2.11. A review of the literature was carried out to identify all patients carrying ABCA12 splice-site and missense variants, and to explore their genotype-phenotype correlations. RESULTS: Genetic testing revealed a nonsense substitution, p.(Arg2204*), and a new missense variant, p.(Val1927Leu), in the ABCA12 gene. After performing in silico analysis and a comprehensive review of the literature, we conclude that p.(Val1927Leu) affects a well conserved residue which could either disturb the protein function or alter the splicing process, both alternatives could explain the severe phenotype of our patient. CONCLUSION: This case expands the spectrum of ABCA12 reported disease-causing variants which is important to unravel genotype-phenotype correlations and highlights the importance of missense variants in the development of HI.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Ictiose Lamelar/genética , Mutação com Perda de Função , Fenótipo , Pré-Escolar , Códon sem Sentido , Humanos , Ictiose Lamelar/patologia , Masculino , Mutação de Sentido Incorreto , Sítios de Splice de RNARESUMO
Self-healing collodion baby is a well-established subtype of this condition. We examined a male newborn, who was covered by a collodion membrane. The shed membrane was examined with scanning electron microscopy. The outer surface showed a very compact keratin without the normal elimination of corneocytes. The lateral view of the specimen revealed a very thick, horny layer. The inner surface showed the structure of lower corneocytes with polygonal contour. With higher magnifications villous projections were seen in the cell membrane.
Assuntos
Ictiose Lamelar/patologia , Microscopia Eletrônica de Varredura/métodos , Humanos , Recém-Nascido , Queratinócitos/patologia , MasculinoRESUMO
AbstractSelf-healing collodion baby is a well-established subtype of this condition. We examined a male newborn, who was covered by a collodion membrane. The shed membrane was examined with scanning electron microscopy. The outer surface showed a very compact keratin without the normal elimination of corneocytes. The lateral view of the specimen revealed a very thick, horny layer. The inner surface showed the structure of lower corneocytes with polygonal contour. With higher magnifications villous projections were seen in the cell membrane.
Assuntos
Humanos , Recém-Nascido , Masculino , Ictiose Lamelar/patologia , Microscopia Eletrônica de Varredura/métodos , Queratinócitos/patologiaRESUMO
El término bebé colodión se refiere a una condición transitoria del recién nacido que consiste en la presencia de una membrana translúcida y adherente que recubre casi completamente la superficie corporal. Constituye una manifestación inicial común a varias entidades; las más frecuentes son la ictiosis lamelar y la eritrodermia ictiosiforme congénita no ampollar. A continuación presentamos una serie de 14 pacientes que nacieron como bebé colodión y una revisión actualizada de la literatura.
Assuntos
Humanos , Recém-Nascido , Recém-Nascido , Ictiose Lamelar/patologia , Ictiose , Pele/patologiaRESUMO
Feto arlequim é uma variante grave da ictiose congenita, uma herança autossômica recessiva que causa alteração da queratinização da pele, que incide em cerca de 1/100.000 nascimentos e está geralmente associada a consaguinidade dos pais. Manifesta-se ao nascimento como uma pele espessada que evolui para rachaduras generalizadas, comprometendo as suas funções básicas e predispondo a infecções. Relata-se o caso de um RN do sexo feminino, cujos pais não referem nenhum grau de parentesco. A mesma foi mantida em isolamento em incubadora, mas feleceu no nono dia de vida por insuficiência respiratória restritiva.
Harlequin fetus is a variant of severe congenital ichthyosis, an autosomal recessive heredity make change in the keratinization of skin, which appear around 1/100.000 births and is usually associated with consaguineus parents. At birth it seems like a thicken skin that develops into widespread cracks, affecting its basics functions and predisposes to infections. We report the case of a female newborn, whose parents dont mention any degree of kinship. The baby stood on isolation in incubator, but died at ninth day of life from restrictive respiratory failure.
Assuntos
Humanos , Feminino , Recém-Nascido , Consanguinidade , Ictiose Lamelar , Recém-Nascido Prematuro , Ectrópio/patologia , Ictiose Lamelar/complicações , Ictiose Lamelar/diagnóstico , Ictiose Lamelar/etiologia , Ictiose Lamelar/genética , Ictiose Lamelar/mortalidade , Ictiose Lamelar/patologia , Ictiose Lamelar/terapia , Recém-Nascido Prematuro/crescimento & desenvolvimentoRESUMO
Os autores relatam um caso de uma criança do sexo feminino com ictose congênita, de pais näo consangüíneos, diagnosticado no Hospital Universitário da UFSC. A paciente apresentava descamaçäo cutânea generalizada e palmo-plantar, ectrópio, eclábio e distrofia ungueais em membros superiores, além de alteraçöes histopatologicas que indicaram o diagnóstico de ictiose lamelar recessiva. O tratamento foi realizado com cremes hidratantes e queratolíticos. Os autores apresentam comentários sobre o diagnóstico diferencial e tratamento das formas mais comuns desta patologia