Ictiosis epidermolítica en un recién nacido: reporte de un caso / Epidermolytic ichthyosis in newborns: clinical case study / Ictiose epidermolítica em recém-nascido: relato de caso

La ictiosis epidermolítica es una genodermatosis de herencia autosómica dominante poco frecuente que requiere un diagnóstico oportuno, idealmente prenatal, para así brindar una asistencia neonatal adecuada, iniciar un tratamiento precoz y de esta manera disminuir su morbimortalidad. Se caracteriza por la formación de ampollas, múltiples erosiones y descamación con eritrodermia desde el nacimiento. Todos los tipos de ictiosis queratinopáticas son causadas por mutaciones en los genes de la familia de queratina KRT1, KRT2 y KRT10. Se presenta el caso clínico de un neonato de 9 días de vida, nacido en el interior del país, con diagnóstico de ictiosis epidermolítica y antecedente familiar de primer grado con la misma enfermedad. El interés de esta publicación radica en la descripción de una genodermatosis de baja frecuencia, reconocer la importancia del diagnóstico precoz, conocer el manejo, las complicaciones y destacar la importancia de la atención por un equipo multidisciplinario conformado por neonatólogo, dermatólogos, genetistas y pediatras.

Epidermolytic ichthyosis is a rare genodermatosis with autosomal dominant inheritance, which requires timely diagnosis, ideally prenatal diagnosis, in order to provide adequate neonatal care, start early treatment and thus reduce morbidity and mortality. It is characterized by the formation of blisters, multiple erosions and scaling with erythroderma from birth. All types of keratinopathic ichthyoses are caused by mutations in the genes of the keratin family KRT1, KRT2 and KRT10. We present the clinical case of a 9-day-old newborn from the interior of the country, with diagnosis and family history of epidermolytic ichthyosis. The interest of this publication lies in the description of a low-frequency genodermatosis, recognizing the importance of early diagnosis, understanding the management, complications and highlighting the importance of a multidisciplinary care team integrated by a neonatologist, dermatologists, geneticists and pediatricians.

A ictiose epidermolítica é uma genodermatose autossômica dominante rara que requer diagnóstico oportuno, idealmente pré-natal, para fornecer cuidados neonatais adequados, iniciar o tratamento precoce e, assim, reduzir sua morbidade e mortalidade. Caracteriza-se pela formação de bolhas, múltiplas erosões e descamação com eritrodermia desde o nascimento. Todos os tipos de ictioses queratinopáticas são causados por mutações nos genes da família da queratina KRT1, KRT2 e KRT10. É apresentado o caso clínico de um recém-nascido de 9 dias, nascido no interior do país, com diagnóstico de ictiose epidermolítica e história familiar de primeiro grau com a mesma doença. O interesse desta publicação reside na descrição de uma genodermatose de baixa frequência, reconhecendo a importância do diagnóstico precoce, conhecendo o manejo, as complicações e destacando a importância do atendimento por uma equipe multidisciplinar composta por neonatologistas, dermatologistas, geneticistas e pediatras.

A rare association of collodion baby with hypothyroidism from tribal area of Jharkhand: a case report

Collodion baby is a rare congenital disorder that resembles the Harlequin foetus but is milder in severity. Although it has been reported that harlequin foetuses are associated with various abnormalities like kidney abnormalities, polydactyly, thymic atrophy, malignant keratoma, and thyroid aplasia, there are few reports of collodion babies associated with congenital abnormalities and/or disease in the literature. The case of a newborn infant admitted with skin shedding and diagnosed with collodion baby concomitant with congenital hypothyroidism is presented here. To the best of our knowledge, this is the first case report of a collodion baby with congenital hypothyroidism in the literature from the tribal region of Jharkhand.

Diagnóstico prenatal de ictiosis arlequín. Comunicación de caso

La ictiosis arlequín, también conocida como queratosis difusa fetal, es un trastorno cutáneo hereditario, extremadamente raro y grave desde el punto de vista fenotípico, con herencia autosómica recesiva. La enfermedad es causada por mutaciones en el gen de la proteína transportadora de casetes de unión a trifosfato de adenosina (ABCA12). La ecografía prenatal y el análisis genético son importantes para el diagnóstico prenatal. El diagnóstico ecográfico prenatal es difícil y los hallazgos incluyen placas de ectropión, pabellón auricular anormal, nariz plana, piel engrosada con apariencia de armadura, labios engrosados con estado sostenido de boca abierta (boca de pez) y fijación en flexión de las extremidades. Estas generalmente son encontradas durante el tercer trimestre. La ecografía tridimensional contribuye a la evaluación de la morfología facial. El pronóstico es generalmente desfavorable. Los neonatos afectados no suelen sobrevivir más allá de los primeros días de vida. Se presenta un caso de diagnóstico prenatal de ictiosis arlequín.

Harlequin ichthyosis, also known as diffuse fetal keratosis, is an extremely rare and phenotypically severe hereditary skin disorder with autosomal recessive inheritance. This disease is caused by mutations in the adenosine triphosphate-binding cassette transporter protein (ABCA12) gene. Prenatal ultrasonography and genetic analysis are important for prenatal diagnosis. Prenatal ultrasonographic diagnosis is difficult, and findings include ectropion plates, an abnormal auricular pinna, a flat nose, thickened skin with an armor-like appearance, thickened lips with sustained open mouth (fish mouth) status, and flexion fixation of the extremities. These are usually found during the third trimester. Three-dimensional ultrasonography contributes to the evaluation of facial morphology. The prognosis is generally poor. Affected neonates usually do not survive beyond the first days of life. A case of prenatal diagnosis of harlequin ichthyosis is presented.

Mutations in CERS3 Gene Underlies a Case of Autosomal Recessive Congenital Ichthyosis / 罕见病研究

Autosomal recessive congenital ichthyosis caused by CERS3 mutations is extremely rare in clinical practice. We recently identified a family of autosomal recessive congenital ichthyosis and performed multigene exome sequencing for hereditary skin diseases to identify causative genes. Mutation analysis revealed compound heterozygous mutations of c.746A>G(from the mother) and exon12 deletion(from the father)in CERS3 were detected in the proband, which were verified by Sanger sequencing and co-segregated with the ichthyosis phenotype in the proband and her parents. These mutations were both reported for the first time. For the treatment, the proband received an oral acitretin capsules of 20 mg once daily. After 3-month follow up, the patient's lesion improved significantly.

Ictiosis vulgar asociada a síndrome de Ehlers Danlos tipo clásico en una niña / Ichthyosis Vulgaris Associated with Ehlers Danlos Syndrome Classic Type in a Girl

Introducción: La ictiosis vulgar y el síndrome de Ehlers Danlos tipo clásico integran dos genodermatosis que presentan en común un patrón de herencia autosómico dominante, pero muestran manifestaciones clínicas variadas. Es infrecuente encontrar concomitancia de ambas dermatosis en un mismo paciente, y cuando ocurre la heterogeneidad clínica hace complejo el diagnóstico. Objetivo: Exponer un caso que presentó ictiosis vulgar asociada con el síndrome de Ehlers Danlos tipo clásico, en el que el análisis del árbol genealógico contribuyó a orientar el diagnóstico. Presentación del caso: Paciente femenina de 10 años de edad, atendida en la consulta especializada de genodermatosis en Las Tunas. Presentaba, desde edades tempranas, lesiones escamosas localizadas en las piernas y brazos, y que empeoraban durante el invierno. Desde los nueve años comenzó a mostrar luxaciones frecuentes de hombro derecho e hiperextensibilidad de la piel. Constaban antecedentes familiares de piel escamosa en miembros de la familia materna e hipermovilidad articular en varios miembros de la familia paterna: El árbol genealógico contribuyó a orientar el diagnóstico y a realizar la atención médica adecuada. Conclusiones: Se trató un caso interesante porque resulta infrecuente encontrar en un mismo paciente dos enfermedades genéticas, lo cual implicó dificultades en el momento de confirmar el diagnóstico, así como su atención. A este diagnóstico, en el caso de ambas genodermatosis, contribuyó el análisis del árbol genealógico familiar, herramienta fundamental en la determinación de enfermedades genéticas(AU)

Introduction: Ichthyosis vulgaris and Ehlers Danlos syndrome classic type comprise two genodermatoses that share an autosomal dominant pattern of inheritance, but show varied clinical manifestations. It is rare to find concomitance of both dermatoses in the same patient, and when this occurs the clinical heterogeneity makes the diagnosis complex. Objective: To present a case of ichthyosis vulgaris associated with classic Ehlers Danlos syndrome, in which analysis of the family tree helped to guide the diagnosis. Case presentation: 10-year-old female patient seen at the specialised genodermatosis clinic in Las Tunas. She presented, from an early age, with scaly lesions located on the legs and arms, which worsened during the winter. From the age of nine he began to show frequent dislocations of the right shoulder and hyperextensibility of the skin. There was a family history of scaly skin in members of the maternal family and joint hypermobility in several members of the paternal family: the family tree helped to guide the diagnosis and appropriate medical care. Conclusions: This was an interesting case because it is rare to find two genetic diseases in the same patient, which implied difficulties at the time of confirming the diagnosis, as well as its care. The analysis of the family tree, a fundamental tool in the determination of genetic diseases, contributed to this diagnosis in the case of both genodermatoses(AU)

A Brazilian case of IFAP syndrome with severe congenital ichthyosis and limb malformations caused by a rare variant in MBTPS2 / Um caso brasileiro de síndrome IFAP com ictiose congênita grave e malformações de membros causadas por uma variante rara em MBTPS2

Abstract Objective: The classic triad, which defines IFAP syndrome, is ichthyosis follicularis, alopecia, and photophobia. It is a rare X-linked genetic disorder characterized by multiple congenital anomalies with variable severity, caused by pathogenic variants in the MBTPS2 gene, which encodes a zinc metalloprotease that is essential for normal development. This study aimed to report a case of a Brazilian patient with IFAP syndrome presenting skeletal anomalies, which is a rare finding among patients from different families. Case description: We describe a male proband with IFAP syndrome showing severe ichthyosis congenita, cryptorchidism, limb malformation, and comprising the BRESHECK syndrome features. Using whole-exome sequencing, we identified a rare missense variant in hemizygosity in the MBTPS2 gene, which had not been identified in other family members. Comments: This is the first diagnosis of IFAP syndrome in Brazil with a molecular investigation. The present case study thus expands our knowledge on the mutational spectrum of MBPTS2 associated with IFAP syndrome.

RESUMO Objetivo: A clássica tríade de ictiose folicular, alopecia e fotofobia dá nome a uma síndrome rara de origem genética com herança ligada ao cromossomo X (síndrome IFAP, do inglês Ichthyosis Follicularis, Alopecia, and Photophobia). Esta é uma síndrome caracterizada por múltiplas anomalias congênitas de expressividade variável, causada por variantes patogênicas no gene MBTPS2, que codifica uma zinco-metaloprotease essencial para o desenvolvimento normal humano. O objetivo deste estudo é apresentar o relato de caso de um paciente brasileiro com síndrome IFAP que apresentou anomalias esqueléticas, um achado raro entre os pacientes de diferentes famílias. Descrição do caso: Apresentamos um probando do sexo masculino com síndrome IFAP, com ictiose congênita grave, criptorquidia, malformação de membros e as características da síndrome de BRESHECK. Por meio do sequenciamento do exoma completo, identificamos uma variante rara do tipo missense, em hemizigose, no gene MBTPS2, não identificada em outros membros da família. Comentários: Este é o primeiro diagnóstico de síndrome IFAP no Brasil com investigação molecular. A análise molecular e a descrição de uma variante rara no gene MBPTS2 expandem nosso conhecimento sobre o espectro mutacional desse gene associado à síndrome IFAP.

Two- and three-dimensional sonographic findings of harlequin ichthyosis: case report and literature review

Abstract Background Harlequin ichthyosis (HI) is a rare skin disorder with extremely high lethality due to a mutation of the ABCA12 gene. Because of its rarity and the often-late onset, prenatal screening for HI is extremely difficult, and most pregnant women might easily miss the period for optimal examinations. Objective To summarize the sonographic features of HI for prenatal diagnostic purposes. Methods The authors describe a case of HI with no family history who was diagnosed by using prenatal ultrasound scanning. The sonographic features of HI and the clinical characteristics of pregnant women were summarized by searching relevant literature over nearly two decades. Results The unique sonographic presentations including peeling skin, clenched hands and clubfeet, ectropion, flat nose, fetal growth impairment, polyhydramnios and echogenic amniotic fluid may be primarily related to skin disorders in HI fetuses. The authors also identified a novel pathogenic ABCA12 gene mutation and explained the possible pathogenic mechanisms. Study limitations Caution should be exercised in summarizing disease characteristics because of the small number of cases, and the authors are faced with the possibility of incomplete case searching. Conclusions HI has relatively unique sonographic features. Therefore, 2D-ultrasound combined with 3D-ultrasound may be an effective method for the prenatal diagnosis of HI. Moreover, a novel pathogenic ABCA12 gene mutation may provide important clues for future research on the etiology of HI. However, the authors consider that additional studies are needed to provide more evidence for prenatal diagnosis.

Metodología para la atención integral a pacientes con genodermatosis

Las genodermatosis constituyen un grupo de enfermedades genéticas con afectación de la piel y sus anexos. En Cuba, el Programa Nacional de Diagnóstico, Atención y Prevención de Enfermedades Genéticas, en relación a las genodermatosis, no cuenta con protocolos para su diagnóstico, tratamiento y seguimiento. El objetivo del estudio es evaluar una metodología para la atención a los pacientes con genodermatosis. Se realizó en Las Tunas, provincia oriental de Cuba, un estudio cuasi-experimental, aplicándose la variante Delphy del método de expertos, siendo consultados un grupo de especialistas cubanos de dermatología, genética médica clínica y pediatría, con alto nivel científico y experiencia en el trabajo con pacientes con genodermatosis. Diseñándose la metodología que propone el protocolo del diagnóstico, tratamiento y algoritmo de seguimiento para estos pacientes. Se estudiaron 395 pacientes atendidos en el Departamento provincial de Genética Médica. Se estudiaron la tasa de prevalencia, la media de casos diagnosticados por año, la proporción de complicaciones presentadas, el índice de supervivencia e índice de letalidad y para relacionar las variables referentes a la mejoría del estado dermatológico y manifestaciones extracutáneas se utilizó la prueba estadística de Chi cuadrado de Mc-Nemar, con una significación estadística p≤0,05. Después de implementada la metodología, predominó la neurofibromatosis 1, síndrome de Ehlers Danlos clásico e ictiosis vulgar, la media de casos diagnosticados por año aumentó; disminuyeron las complicaciones, predominando las piodermitis (6.13 %); el índice de mortalidad fue bajo (1.27%) con alto índice de supervivencia (98.73%) y mejoría de las manifestaciones dermatológicas (MCNemar X2=90.41558, P=0.000000) y extracutáneas (McNemar X2=24.083334, P=0.000001). La metodología diseñada para la atención a pacientes con genodermatosis fortalece el Programa Nacional de Diagnóstico, Atención y Prevención de Enfermedades Genéticas, demostrando ser efectiva, con mayor número de casos diagnosticados, menor proporción de complicaciones, alta supervivencia, baja letalidad y mejoría clínica de las manifestaciones dermatológicas y extracutáneas.

The genodermatoses constitutes a group of genetic diseases with affectation of the skin and their annexes. In Cuba, the National Program of Diagnostic, Attention and Prevention of Genetic diseases, in relation to the genodermatoses, don't have protocols for their diagnosis, treatment and pursuit. The objective of this study is to evaluate a methodology for the attention to the patients with genodermatosis. Was carried out in The Tunas, oriental county of Cuba, a quasi-experimental study, being applied the varying Delphy of the method of experts, being consulted a group of Cuban specialists of dermatology, genetics clinical doctor and pediatrics, with high scientific level and experience in the work with patient with genodermatoses. Being designed the methodology that proposes the protocol of the diagnosis, treatment and pursuit algorithm for these patients. 395 patients were studied assisted in the provincial Department of Medical Genetics. Were studied the prevalence rate, the stocking of cases diagnosed per year, the proportion of presented complications, the index of survival and lethality index and to relate the relating variables to the improvement of the state dermatologic and extracutaneous manifestations the statistical test of square Chi of Mc-Nemar was used, with a significance statistical p≤0,05. After having implemented the methodology, prevailed the neurofibromatosis, Ehlers Danlos syndrome and ichthyosis vulgaris; the stocking of cases diagnosed per year increased; they diminished the complications, prevailing the piodermitis (6.13%); the index of mortality was low (1.27%) with high index of survival (98.73%) and improvement of the manifestations dermatologic (MCNemar X2=90.41558, P=0.000000) and extracutaneous (McNemar X2=24.083334, P=0.000001). The methodology designed for the attention to patient with genodermatoses strengthens the National Program of Diagnostic, Attention and Prevention of Genetic Illnesses, demonstrating to be effective, with bigger number of diagnosed cases, smaller proportion of complications, high survival, low lethality and clinical improvement of the dermatologic and extracutaneous manifestations.

As genodermatoses são um grupo de doenças genéticas com envolvimento da pele e seus anexos. Em Cuba, o Programa Nacional de Diagnóstico, Cuidado e Prevenção de Doenças Genéticas, em relação às genodermatoses, não possui protocolos para seu diagnóstico, tratamento e acompanhamento. O objetivo do estudo é avaliar uma metodologia para o cuidado de pacientes com genodermatose. Um estudo quase-experimental foi realizado em Las Tunas, província oriental de Cuba, aplicando a variante Delphy do método expert, sendo consultado um grupo de especialistas cubanos em dermatologia, genética médica clínica e pediatria, com alto nível científico e experiência no trabalho com pacientes com genodermatose. Desenho da metodologia que propõe o protocolo de diagnóstico, tratamento e algoritmo de acompanhamento para esses pacientes. Um total de 395 pacientes tratados no Departamento Provincial de Genética Médica foram estudados. Foram estudadas as prevalências, o número médio de casos diagnosticados por ano, a proporção de complicações apresentadas, a sobrevida e o índice de letalidade e para relacionar as variáveis referentes à melhora do estado dermatológico e das manifestações extracutâneas, utilizou-se o teste estatístico Qui-quadrado de Mc-Nemar, com significância estatística p≤0, 05. Após a implementação da metodologia, predominaram a neurofibromatose 1, a síndrome clássica de Ehlers Danlos e a ictiose vulgar, aumentando-se o número médio de casos diagnosticados por ano; complicações diminuídas, predominantemente piodermite (6,13%); a taxa de mortalidade foi baixa (1,27%), com alta sobrevida (98,73%) e melhora dermatológica (MCNemar X2=90,41558, P=0,000000) e extracutânea (McNemar X2=24,083334, P=0,000001). A metodologia desenhada para o cuidado de pacientes com genodermatose fortalece o Programa Nacional de Diagnóstico, Cuidado e Prevenção de Doenças Genéticas, mostrando-se eficaz, com maior número de casos diagnosticados, menor proporção de complicações, alta sobrevida, baixa letalidade e melhora clínica das manifestações dermatológicas e extracutâneas.

Ictiosis Laminar. Un caso familiar recurrente

Introducción: Las ictiosis hereditarias pueden ser sindrómicas y no sindrómicas, estas últimas, de acuerdo con la expresión fenotípica cutánea, incluyen, ictiosis comunes, ictiosis recesiva ligada al cromosoma X, ictiosis congénita autosómica recesiva, ictiosis queratinopática y otras formas. La ictiosis congénita autosómica recesiva, incluye tres fenotipos principales: La ictiosis arlequín, ictiosis laminar y eritrodermia ictiosiforme congénita. Comunicamos un caso clínico de ictiosis laminar recurrente en una familia. Reporte de caso: Recién nacido pretérmino, tiene hermana de 6 años, con diagnóstico de ictiosis lamelar. Madre niega consanguinidad con esposo, y parientes con esta enfermedad. Al nacer se observa cubierto de membrana colodión en toda la piel, ectropión y eclabio. El manejo inicial, fue gasa vaselinada, lagrimas artificiales, gasas húmedas en los ojos. Actualmente baños con crema de ducha, Shampoo y Aceite mineral, cremas y loción hidratantes y Acitretina, está en franca mejoría. Conclusiones: Con la historia clínica y los antecedentes familiares es posible diagnosticar ictiosis laminar. El manejo es multidisciplinario.

Introduction: Hereditary ichthyosis can be syndromic and non-syndromic, the latter, according to the cutaneous phenotypic expression, include common ichthyosis, X-linked recessive ichthyosis, autosomal recessive congenital ichthyosis, keratinopathic ichthyosis and other forms. Autosomal recessive congenital ichthyosis includes three main phenotypes: harlequin ichthyosis, lamellar ichthyosis, and congenital ichthyosiform erythroderma. We report a clinical case of recurrent lamellar ichthyosis in a family. Case Report: Preterm newborn, has a 6-year-old sister, diagnosed with lamellar ichthyosis. Mother denies consanguinity with husband, and relatives with this disease. At birth, it is observed covered with collodion membrane throughout the skin, ectropion and eclabio. The initial management was Vaseline gauze, artificial tears, wet gauze in the eyes. Currently baths with shower cream, Shampoo and mineral oil, moisturizing creams and lotions and Acitretin, is clearly improving. Conclusions: With the medical history and family history it is possible to diagnose lamellar ichthyosis. Management is multidisciplinary.

Harlequin fetus: A case report

Harlequin ichthyosis (HI) is the most severe type of congenital ichthyosis. It is extremely rare with very few cases reported in India. It is inherited in an autosomal recessive fashion. The importance of antenatal diagnosis by ultrasonography, DNA-based molecular studies on chorionic villus sampling, and amniocentesis has been emphasized. We report a new case of HI in an infant, diagnosed postnatally by correlation of clinical and histopathological features on skin biopsy. The infant succumbed on the second day of birth despite intensive supportive care. A short review of the literature regarding the condition is also presented.

Harlequin Ichthyosis: Folklore of Demon

Background: Harlequin ichthyosis (HI) is a severe and rare autosomal recessive congenital ichthyosis, characterized by severe hyperkeratosis, extensive fissuring and massive, diamond-shaped scales which limit the child’s movements. The term harlequin comes from the baby’s facial expression and diamond-shaped pattern of the scales like the 17th century entertainers, harlequins. The underlying genetic abnormality has been identified as a mutation in the lipid-transporter gene ABCA 12 on chromosome 2q35. Aim and objectives: To provide a comprehensive knowledge of severe forms of congenital ichthyosis, the harlequin ichthyosis and abolish the superstitious notion regarding the appearance of the neonate. Materials and Methods: The present report is case of premature girl baby delivered at MIMS, Mandya. The neonate presented plaques of rigid fixed skin, separated by deep red fissures, facial features were obliterated by thickened skin, undeveloped nose and pinna, severe ectropion and eclabium. Intensive care was given and survival was prolonged by systemic retinoids. The neonate succumbed to respiratory failure few days later. Results and conclusion: The present study gives a comprehensive knowledge of harlequin ichthyosis and provides emphasis on sensitization of the disease to prevent any misconception or superstition. Also lays emphasis on Genetic counseling of the couple to prevent further occurrences.

Ictiosis arlequín en un neonato / Arlekin ichthyosis in a newborn baby

Se describe el caso clínico de un neonato, producto de parto eutócico, a término y normopeso, asistido en el Hospital Distrital de Barrillas, perteneciente a la zona rural del Departamento Huehuetenango en Guatemala, que al nacer presentó escamas grandes y gruesas diseminadas en la piel, así como eversión de párpados y labios. Se le diagnosticó ictiosis arlequín, por lo que se mantuvo ingresado en la Unidad de Cuidados Neonatales de dicho centro. La evolución fue desfavorable, con persistencia de complicaciones, tales como sepsis grave y alteraciones hidroelectrolíticas, a pesar del tratamiento médico, por lo que falleció a los 6 días de nacido e igual período de hospitalización.

The case report of a newborn baby, product of an eutocic childbirth, at term and normal weight, is described. He was assisted in Barrillas Distrital Hospital, belonging to the rural area of the Huehuetenango Department in Guatemala due to big and thick flakes disseminated in the skin when being born, as well as eversion of eyelids and lips. Arlekin ichthyosis was diagnosed, reason why he was admitted to the Neonates Care Unit of this center. The clinical course was unfavorable, with persistence of complications, such as serious sepsis and hydroelectrolitic disorders, in spite of the medical treatment, reason why he died after 6 days of being born and same period of hospitalization.

Early warning of low maternal unconjugated estriol level by prenatal screening for fetus with X-linked ichthyosis / 中华妇产科杂志

Objective:To analyze the characteristic of prenatal serological screening in fetus with X-linked ichthyosis (XLI), and to explore the relationship between unconjugated estriol (uE 3) levels and XLI. Methods:A total of 56 fetuses with Xp22.31 microdeletion indicated by prenatal diagnosis and 70 fetuses diagnosed with trisomy 21 and 26 fetuses with trisomy 18 in Henan Provincial People's Hospital and Affiliated Hospital of Weifang Medical College from September 2016 to June 2021 were collected. The multiples of median (MoM) values of uE 3, alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) during the second trimester of pregnancy were retrospectively analyzed. Prenatal diagnosis was made by amniotic fluid karyotype analysis and genome copy number variant analysis, parent genetic verification and pathogenicity analysis were performed, and maternal and infant outcomes were followed up. Results:Of 56 pregnant women with fetal Xp22.31 microdeletion, 43 underwent serological screening during the second trimester of pregnancy, of which 42 were abnormal (39 male fetuses and 3 female fetuses). The median uE 3 MoM value of 39 male fetuses [0.06 (0.00-0.21)] was lower than the normal value and significantly lower than that of fetuses with trisomy 21 [0.71 (0.26-1.27)] and fetuses with trisomy 18 [0.36 (0.15-0.84)], the difference was statistically significant ( Z=99.96, P<0.001). While the MoM values of AFP and hCG were all within the normal range. Among the 56 fetuses carrying Xp22.31 microdeletion, 45 were male fetuses and 11 were female fetuses, and the deletion fragments all involved STS gene. Eighty-nine percent (50/56) were inherited from mother (49 cases) or father (1 case), and 11% (6/56) were de novo mutations. Follow-up showed 48 live births (38 males and 10 females) and 8 chose to terminate pregnancy (7 males and 1 female). Among the 38 male newborns, 37 presented with scaly skin changes from 1 to 3 months of age, and one had no clinical manifestations until 4 months after birth. Ten female newborns had no obvious clinical manifestations. Conclusions:The decrease levels of uE 3 MoM on maternal serological screening is closely related to the higher risk of XLI in male fetuses. For pregnant women with low uE 3 in serological screening or with family history of ichthyosis, in addition to chromosomal karyotype analysis, joint detection of genomic copy number variant analysis should be recommended.

A novel mutation in the ALOX12B gene in hereditary ichthyosis: pedigree analysis for a female collodion baby / 中华皮肤科杂志

Objective:To investigate pathogenic genes and inheritance patterns in 3 consecutive collodion babies in a family.Methods:The proband was diagnosed as a collodion baby due to extensive dry and chapped skin all over the body at birth. Phenotypes of the proband's parents were normal, but their first and second children presented with dry and chapped skin at birth and died a few days after birth. DNA was extracted from peripheral blood samples of the patient and her parents for whole-exome capture sequencing, and candidate mutations were verified by Sanger sequencing.Results:Compound heterozygous mutations in the ALOX12B gene were identified in the infant, including a missense mutation c.1405 C>T (p.R469w) inherited from her father and a frameshift mutation c.68_69insC (p.L24fs) inherited from her mother.Conclusions:The infant was diagnosed with hereditary ichthyosis, which was inherited in an autosomal recessive manner. The missense mutation c.1405 C>T and frameshift mutation c.68_69insC in the ALOX12B gene may contribute to the clinical phenotype of this infant, and the frameshift mutation had not been reported in China or other countries.

Mutation analysis of the PNPLA1 gene in three families with congenital ichthyosiform erythroderma / 中华皮肤科杂志

Objective:To detect gene mutations in 3 Chinese families with congenital ichthyosiform erythroderma.Methods:Exome sequencing of peripheral blood DNA was performed for 3 probands clinically diagnosed with congenital ichthyosiform erythroderma by using a gene panel targeting hereditary skin diseases to identify mutation sites. Primers were designed according to the mutation sites for PCR amplification, and Sanger sequencing was performed to verify the mutations in probands and other family members in order to identify the cause of the disease.Results:The probands 1 and 2 presented with generalized skin dryness and scaling, and polygonal dark brown scales on the extensor aspect of the lower limbs; the proband 3 mainly presented with well-circumscribed erythema, papules and scales scattered on the trunk and extremities. All probands denied family history of similar diseases. Genetic testing showed that the proband 1 carried compound heterozygous mutations c.100G>A and c.377G>A in the PNPLA1 gene, which were inherited from her mother and father respectively; the proband 2 carried compound heterozygous mutations c.320T>A and c.434T>C in the PNPLA1 gene, which were inherited from her mother and father respectively; a homozygous mutation c.1300delG was identified in the PNPLA1 gene in the proband 3. The mutations co-segregated with the disease phenotypes in the two families with compound heterozygous mutations. Among the 5 identified mutations, the two missense mutations (c.377G>A and c.320T>A) were firstly reported.Conclusion:Biallelic mutations in the PNPLA1 gene are the causative mutations responsible for autosomal recessive congenital ichthyosis in the three probands, and the newly reported mutations expand the mutation spectrum in the disease.

Novel Pathogenic Mutation of PNPLA1 Identified in Autosomal Recessive Congenital Ichthyosis: A Case Report / 中国医学科学杂志(英文版)

Autosomal recessive congenital ichthyosis (ARCI) is characterized by being born as collodion babies, hyperkeratosis, and skin scaling. We described a collodion baby at birth with mild ectropion, eclabium, and syndactyly. Whole exome sequencing showed a compound heterozygous variant c.[56C>A], p.(Ser19X) and c.[100G>A], p.(Ala34Thr) in the PNPLA1 gene [NM_001145717; exon 1]. The protein encoded by PNPLA1 acts as a unique transacylase that specifically transfers linoleic acid from triglyceride to ω-hydroxy fatty acid in ceramide, thus giving rise to ω-O-acylceramide, a particular class of sphingolipids that is essential for skin barrier function. The variant was located in the patatin core domain of PNPLA1 and resulted in a truncated protein which could disrupt the function of the protein. This case report highlights a novel compound heterozygous mutation in PNPLA1 identified in a Chinese child.

Mutation Analysis of the CYP4F22 Gene in a Family with Autosomal Recessive Congenital Ichthyosis / 罕见病研究

Autosomal recessive congenital ichthyosis (ARCI) is a rare hereditary cornification disorder presented with abnormal skin scaling. In this paper, we used next-generation sequencing to determine the variants in a Chinese ARCI patient. We used sanger sequencing to verify bidirectionally the DNA from the proband and her parents. Results showes that two compound heterozygous variants (c.235G > T and c.641delG) in CYP4F22 gene, and both of the mutations are novel. The parents were heterozygous carriers. The two variants are classified as pathogenic variants based on interpretation guidelines. The compound heterozygous mutations in CYP4F22 gene were the causative mutations responsible for ARCI in proband.

Prenatal diagnosis of a fetus with harlequin ichthyosis caused by novel splice-site mutation in ABCA12 gene / 中华围产医学杂志

This article reported a rare case of harlequin ichthyosis which was indicated with multiple structural abnormalities by prenatal ultrasound and diagnosed by trio-based whole-exome sequencing (Trio-WES). Prenatal diagnosis was performed because the ultrasound at 24 +4 gestational weeks revealed the fetus presenting with eclabium, flattened nose, short mandible, small auricle and abnormal posture of the toes. Copy number variation sequencing (CNV-seq) showed no chromosome aneuploidy or pathogenic copy number variants over 100 kb in the fetal or parental samples. Trio-WES showed that the fetus carried two heterozygous mutations, c.2593-1G>A and c.7444C>T in ABCA12. Sanger sequencing confirmed that c.2593-1G>A, a previously unreported variant, was paternally inherited and c.7444C>T was maternally inherited. Both parents had normal phenotype. The fetus was finally diagnosed with harlequin ichthyosis. After prenatal counseling, the parents made an informed choice to terminate the pregnancy at 28 +4 gestational weeks. The stillborn fetus showed multiple malformations The variants in this case expand the spectrum of variants in ABCA12 gene.

Aproximación diagnóstica ultrasonográfica prenatal al síndrome de Omenn: reporte de caso / Prenatal ultrasound diagnostic approach to Omenn syndrome: case report

Objetivo: reportar el caso de una gestante con diagnóstico ultrasonográfico de alteración del sistema tegumentario fetal y diagnóstico posnatal de síndrome de Omenn. Presentación de caso: se presenta el caso de paciente de 27 años con embarazo de 31 semanas, con exploración ultrasonográfica prenatal que evidencia feto con edema significativo del cuero cabelludo, líquido amniótico ecogénico y descamación de la piel abdominal, con aproximación diagnóstica ultrasonográfica de variante de ictiosis. El recién nacido presentó eritrodermia congénita complicada con infección de piel, con posterior choque séptico y muerte. El estudio genético y patológico concluye síndrome de Omenn. Conclusión: el síndrome de Omenn debe ser tomado en cuenta en los diagnósticos diferenciales cuando en la ultrasonografía prenatal existan hallazgos ultrasongráficos de una alteración del sistema tegumentario. Se requieren estudios que evalúen la exactitud del ultrasonido en el diagnóstico antenatal de las eritrodermias.

Objective: To report the case of a pregnant woman with ultrasound diagnosis of altered fetal tegumental system and postnatal diagnosis of Omenn syndrome. Case presentation: A 27-year-old patient who presented at 31 weeks of gestation with prenatal ultrasound evidence of a fetus with significant scalp edema, echogenic amniotic fluid and scaly abdominal skin, with ichtyosis variant impression on diagnostic ultrasound. The baby was born with congenital erythroderma complicated with skin infection, and later developed septic shock and died. The genetic and pathologic workup led to the conclusion of Omenn syndrome. Conclusion: Omenn syndrome must be considered as part of the differential diagnoses when prenatal ultrasound shows findings of altered tegument system. Studies are required to assess the accuracy of ultrasound for prenatal diagnosis of erythroderma.