Dyskeratosis congenita and a rare brain abscess / Disqueratosis congénita y absceso del sistema nervioso central

Abstract Dyskeratosis congenita is a rare inheritable disease which causes peculiar dermatological features and bone marrow failure with an increased risk of severe infections and neoplasia. Actinomyces spp. is part of the oral cavity flora. Invasive infections are mostly seen in immunocompromised hosts. We report a case of a rare central nervous infection and an underling inheritable disease.

Resumen La disqueratosis congénita es una enfermedad hereditaria, caracterizada por alteraciones cutáneas y aplasia medular. La principal causa de muerte son las infecciones y el desarrollo de neoplasias. Actinomices spp. son patógenos comensales de la cavidad oral y el tracto urinario, que en raras ocasiones suelen causar infecciones invasivas en el ser humano. Suelen ser más frecuentes en pacientes inmunocomprometidos o con mala higiene dental. Presentamos el caso de una lesión ocupante de espacio a nivel del sistema nervioso central con una inmuno deficiencia heredable.

Dyskeratosis congenita

Dyskeratosis congenita (DC) is a genetic syndrome with progressive multisystem involvement classically characterized by the clinical triad of oral leukoplakia, nail dystrophy, and reticular hyperpigmentation. Frequent complications are bone marrow failure, increased rate of malignancy, lung and liver diseases. DC results from an anomalous progressive shortening of telomeres resulting in DNA replication problems inducing replicative senescence. We report a death due to DC in a 16-year-old male with bone marrow failure and multiple organ dysfunction. At autopsy, nail dystrophy and skin hypopigmentation were observed. Gross and microscopic examinations of the internal organs showed cardiac hypertrophy, multiple lung consolidations and prominent interstitial fibrosis, liver cirrhosis, and fibrosis. Multiple foci of extramedullary hematopoiesis were identified, including on the epidural surface of the dura, that is an infrequent location, mimicking a focal area of epidural hemorrhage. Only a few autopsy studies about DC are reported in the literature. Further research should be done to understand the pathophysiology of the disease and its complications.

Research progress of dyskeratosis congenita / 中华口腔医学杂志

Dyskeratosis congenita (DC) is a rare disease and a genetic heterogeneity of bone marrow failure, characterized by muco-cutaneous triad of mucosal leukoplakia, abnormal skin pigmentation, nails dystrophy and often involving multiple organs or systems. The inheritance patterns of DC include X-linked recessive, autosomal dominant and recessive patterns. However, the inheritance patterns in 30%-40% of DC patients remained unknown. Dyskeratosis congenita is difficult to diagnose because of its genetic and clinical heterogeneity. This article will review and discuss the state-of-the-art progresses in genetics, clinical manifestation, diagnosis, differential diagnosis, treatment and prognosis of DC.

Diagnosis and treatment of dyskeratosis congenita in Chinese children / 中华实用儿科临床杂志

Objective To analyze and summarize the characteristics of Dyskeratosis congenita(DC)in Chinese children,so as to provide reference for early diagnosis and reasonable prevention and treatment of DC.Methods The data collected from 43 cases with DC in the domestic literature in recent 10 years,as well as the clinical data of 2 cases with DC treated at Tongji Hospital,Medical School,Tongji University,and a total of 45 cases with DC were analyzed and compared with those reported in the literatures of foreign countries.Results Based on the detailed data of 2 typical cases at Tongji Hospital,Medical School,Tongji University,and the data of 45 cases in China were summarized,so the major differences in the main characteristics of DC between Chinese Children and the foreigners were as follows:(1)Onset were earlier(mean age 4.5 years,median age of 3 years),but the diagnosis was delayed(mean age of 17.9 years,median age of 18 years).(2)The presence of skin pigmentation,nail lesions and mucosal leukoplakia,such as the proportion of the complete DC triad was higher(42/45 cases,93.3％).(3)There was an earlier onset of hematopoietic suppression(mean age 5.6 years).(4)Telomerase related gene mutation types were relatively minor,DKC1(7 cases)and TINF2(6 cases)were reported in recent years,and no other type of mutation was found.(5)Effective therapy of hematopoietic reconstitution was administered in 2 cases after allogeneic hematopoietic stem cell transplantation(allo-HSCT).The effective rates were about 70％(7/10 cases)in treating bone marrow failure with low dose androgen and low dose glucocorticoid.Conclusions DC is very common in infants in China,the clinical manifestations of triad are more typical,but the age of diagnosis was significantly delayed.Improving the understanding of DC and combination with the detection of related gene mutation may improve the early diagnosis rate and clinical efficacy with allo-HSCT or effective drug maintenance therapy,and also provide reference for propitious familial eugenics and prenatal examination.

Disceratose congênita - relato de caso e revisão de literatura / Dyskeratosis congenita - case report and literature review

A Disceratose Congênita (DC) é uma síndrome hereditária rara que exibe marcada heterogeneidade clínica e genética, constituindo-se em anormalidades cutaneomucosas, falência medular e predisposição ao câncer. Esta é caracterizada pela tríade de pigmentação reticulada da pele, distrofia ungueal e leucoplasia em mucosas. Alterações dentárias, gastrintestinais, geniturinárias, neurológicas, oftalmológicas, pulmonares e esqueléticas associadas têm sido relatadas. A falência medular é a principal causa de morte precoce e também é descrita predisposição para doenças malignas. Afeta principalmente homens e, reconhecem-se formas recessivas ligadas ao X, autossômicas dominantes e recessivas. Relata-se o caso de um paciente de 40 anos, sexo masculino, que há 7 evolui com quadro de anemia e necessidades transfusionais (sanguíneas). Investigadas causas hemofílica e carencial sem êxito. Mielograma com normocelularidade das linhagens; solicitada biópsia de medula óssea por suspeita de Disceratose Congênita, tendo em vista sintomatologia com presença da tríade da Disceratose Congênita: leucoplasia mucosa, distrofia ungueal, e áreas de hiperpigmentação reticular. Paciente progride sob acompanhamento no serviço hematológico do Hemocentro do Pará. Em função da raridade da doença, pouco mais de 500 casos relatados no mundo, da dificuldade de se chegar ao seu diagnóstico, e de sua gravidade, é de fundamental importância a difusão do conhecimento e ratifica-se a necessidade do acompanhamento médico multidisciplinar, de modo a permitir diagnóstico e tratamento precoce das possíveis complicações.

Dyskeratosis Congenita (DC) is a rare hereditary syndrome that shows marked clinical and genetic heterogeneity, like mucocutaneous abnormalities, bone marrow failure and predisposition to cancer. Dyskeratosis congenita triad is: abnormal skin pigmentation, nail dystrophy and mucosal leukoplakia. Dental, gastrointestinal, genitourinary, neurological, ophthalmic, pulmonary and skeletal disorders have been reported. The leading cause of early death and an additional predisposition to malignancy is bone marrow failure. Dyskeratosis congenita mainly affects men and recessive X-linked, autosomal dominant and recessive forms are recognized. We report the case of a 40-year-old male, 7 years evolving symptoms of anemia and transfusion requirements. Unsuccessfully research by deficiency causes and hemophilia were done. Normal cellular lineages myelogram. Patient progresses under supervision of Hemocenter of Pará (HEMOPA). Depending on the rarity of the disease, little more than 500 cases reported worldwide, the difficulty of arriving at a diagnosis, and its severity, is crucial to spreading knowledge and it confirms the need for a multidisciplinary approach, the to enable early diagnosis and treatment of possible complications.

Malrotation of Gut and Hiatus Hernia in a Child with Familial Dyskeratosis Congenita.

Dyskeratosis congenita (DKC) is a rare inherited genodermatosis. We report familial occurrence of the disease. The index patient 12 years old had all classical features of DKC. There are 4 other siblings in the family suffering from similar disease. In additions to the features of DKC, the index patient presented with pain abdomen and vomiting. On investigation he had malrotation of gut and hiatus hernia. To the best of our knowledge this is being documented for the first time in association with DKC.

Vohwinkel syndrome, ichthyosiform variant - by Camisa - Case report / Sindrome de Vohwinkel, variante ictiosiforme - de Camisa - Relato de caso

Vohwinkel syndrome or keratoderma hereditaria mutilans is a rare autosomal dominant palmoplantar keratosis, which manifests in infants and becomes more evident in adulthood. Its mode of inheritance is autosomal dominant with mutation in loricrin and Connexin 26 genes. Patients with this mutation present hyperkeratosis of the palms and soles, constricting bands of the digits, usually on the fifth, and starfish-shaped hyperkeratosis on the dorsal aspects of the hands and feet. The disease mostly occurs in white women, where constricting fibrous bands appear on the digits and can lead to progressive strangulation and auto-amputation (pseudo-ain-hum).The authors report a rare case of a patient with a clinical ichthyosiform variant of Vohwinkel syndrome.

A síndrome de Vohwinkel ou queratodermia hereditária mutilante é uma queratose palmo-plantar rara, autossômica dominante, que se manifesta em crianças e se torna mais evidente na vida adulta. Seu modo de herança é autossômica dominante com mutação na loricrina e no gen da Conexina 26. Os pacientes com esta mutação apresentam hiperqueratose das palmas das mãos e plantas dos pés, com bandas constritivas dos dígitos, normalmente no quinto dedo e hiperqueratose em forma de estrela do mar nas regiões dorsais das mãos e dos pés. A doença ocorre principalmente em mulheres brancas, onde as bandas constritivas fibrosas aparecerem nos dígitos e podem levar ao estrangulamento progressivo e auto-amputação (pseudo-ainhum).Os autores relatam o caso de uma variante ictiosiforme da síndrome de Vohwinkel.

Interstitial Lung Disease in a Patient with Dyskeratosis Congenita / 결핵및호흡기질환

Dyskeratosis congenita is a rare congenital disorder characterized by a triad of reticular pigmentation of the skin, dystrophic nails, and leukoplakia of the mucous membrane. Sometimes it is associated with bone marrow failure, secondary malignancy and interstitial lung disease. Though it is rare, Dyskeratosis congenita is diagnosed relatively easily when clinicians suspect it. It can be diagnosed just by gross inspection with care. Dyskeratosis congenita should be considered as one cause associated with interstitial lung disease. In Korea, interstitial lung disease with dyskeratosis congenita has not been reported. We report a case and review the literature.

Identification of DKC1 gene mutation in an indian patient.

Dyskeratosis congenita - X-linked variety was diagnosed in a twelve year old male child with cutaneous pigmentary changes and dystrophic changes in nails of hands and feet. His elder brother had similar nail changes and had died at twelve yr of age. We demonstrated the A353V mutation in the proband after sequencing the DKC1 gene. The mother was found to be carrier for the same mutation. She did not have any clinical manifestations. This is the commonest mutation worldwide responsible for X-linked variety of this disease and has been demonstrated for the first time in an native Indian patient.

Disqueratosis congénita ligada al cromosoma X / X-linked congenital dyskeratosis

La disqueratosis congénita es una genodermatosis muy poco frecuente, existiendo aproximadamente 180 casos reportados. Objetivo: Presentar el caso de un paciente de sexo masculino en quien se sospechó el diagnóstico basado en la presentación clínica, confirmado posteriormente mediante estudio molecular. Caso clínico: Escolar de sexo masculino con antecedentes de anemia refractaria a tratamiento e infecciones bacterianas severas, que se presentó clínicamente con hiperpigmentación cutánea reticular, distrofia ungueal, leucoplaquia y falla medular. En el estudio molecular se detectó una mutación del gen DKC1 que determina una sustitución aminoacídica en la posición 353 de Alanina por Valina. Discusión: La disqueratosis congénita es un desorden genético multisistémico, muy poco frecuente. Clínicamente se caracteriza por la presencia de hiperpigmentación cutánea de tipo reticular, distrofia ungueal, leucoplaquia de la mucosa oral y pancitopenia progresiva. La mutación detectada en este caso es una causa importante de Disqueratosis congénita en el mundo.

Dyskeratosis congenita is a rare genetic disorder with approximately 180 cases reported in the literature. Objective: To present the case of a boy, in whom the diagnosis was clinically suspected and later confirmed by molecular analysis of the Dyskerin gene. Clinical Case: A school age boy with a history of anemia resistant to treatment, and severe bacterial infections, who presented with reticulated pigmentation of the skin, nail dystrophy, oral leukoplakia and progressive pancitopenia. Molecular analysis revealed a mutation in the DKC1 gene, that results in an aminoacid change from alanine to valine. Conclusion: Dyskeratosis congenita is a rare inherited disease characterised by cutaneous reticulated hyperpigmentation, nail dystrophy, oral leukoplakia and progressive pancytopenia. The mutation detected in this patient is an important cause of dyskeratosis congenita worldwide.

Dyskeratosis Congenita in a Girl / 대한소아혈액종양학회지

Dyskeratosis congenita (DC) is a rare genetic disorder encompassing abnormal skin pigmentation, dystrophic nails, leukoplakia of mucous membranes and others. Bone marrow failure is the cause of early mortality. Moreover, DC is known for its predisposition to malignancy. X-linked recessive, autosomal dominant and autosomal recessive forms of the disease are recognized. We describe here a rare case of DC in a 4-year-old girl showing dark skin, dystrophic toe nails, and mild bone marrow failure. Autosomal recessive disease was suggested as the patient is female, and tests for DKC1 and hTR mutations were negative. Intermittent treatment with oxymetholone and prednisolone for about 26 months resulted in stable hemoglobin and platelet response.

Dyskeratosis Congenita / 대한피부과학회지

Dyskeratosis congenita is a rare multisystemic genodermatosis of ectodermal dysplasia, and is characterized by the diagnostic triad consisting of reticulated hyperpigmentation, dystrophic nails, and leukoplakia. Complications such a malignancy and bone marrow involvement will be predisposition. A 44-year-old male was presented with reticulated hyperpigmentation, nail dystrophy, oral leukoplakia, mild hyperkeratosis of the palms and soles, and short stature. His brothers were presented with reticulated hyperpigmentation and nail dystrophy, and underwent a surgical operation due to oral cavity cancer. The histopathological findings taken from the reticulated lesion showed epidermal thinning and a mild inflammatory cell infiltration with melanophages in the dermis. We report a typical case of dyskeratosis congenita in a male with family history.

A Case of Dyskeratosis Congenita

Dyskeratosis congenita is a rare genodermatosis of ectodermal dysplasia, which is characterized by the diagnostic triad consisting of reticulated hyperpigmentation, dystrophic nails, and leukoplakia. There is a predisposition to malignancy, particularly at sites of leukoplakia. Bone marrow failure can occur in about a half of the cases. A 16-year-old boy was presented with asymptomatic reticulated pigmentation of the neck and nail dystrophy. The patient also had leukoplakia on the tongue, nasolacrimal duct obstruction and cataract. The histopathological findings taken from the reticulated lesion were consistent with poikiloderma atrophicans vasculare. These clinical and histopathological findings were typical features of dyskeratosis congenita.

A Case of Dyskeratosis Congenita with Myelodysplastic Syndrome / 대한혈액학회지

Dyskeratosis congenita is a rare form of ectodermal dysplasia consisting of dystrophic nails, reticular hyperpigmentation and leukoplakia, that is often associated with aplastic anemia. We have experienced a 17 year-old-man who had reticular pigmentation of the skin and dystrophic changes of the fingers and toe nails. The tongue was smooth and lingual papillae disappeared with formation of adherent white leukoplakic patches. Laboratory data revealed pancytopenia. Bone marrow study showed mild hypocellular marrow with dyserythropoiesis, suggesting the refractory anemia of myelodysplastic syndrome. We report one case of dyskeratosis congenita with myelodysplastic syndrome with a review of literature.

Mutation of DKC1 Gene in a Family of Dyskeratosis Congenita / 中华皮肤科杂志

Objective To identify the mutation of DKC1 gene and its inheritance in a pedigree with dyskeratosis congenita (DKC). Methods The mutation was detected by polymerase chain reaction(PCR)and DNA sequencing, and restriction endonuclease digestion was performed to confirm the mutation. Results A transition mutation of C to T (1058C-T) in DKC1 gene was found in the proband and his brother. This mutation results in an amino acid change from alanine to valine (A353V) in dyskerin protein. The proband′s mother and sister were carriers of this mutation gene with no phenotype of DKC. Conclusion This pedigree is an X-linked form of DKC with 1058C-T mutation in DKC1 gene.

A novel mutation in DKC1 gene in a patient with dyskeratosis congenita / 中华皮肤科杂志

Objective To detect the mutation in DKC1 gene in a patient with dyskeratosis congeni- ta.Methods Fifteen exons of DKC1 gene were amplified by polymerase chain reaction (PCR),and the products were screened for mutations by denaturing high performance liquid chromatography (DHPLC) technology,then DNA sequencing was performed for abnormal exons as shown by DHPLC.The gene muta- tions were verified within 100 unrelated male individuals without dyskeratosis congenita.Results An ab- normal DHPLC elution peak was found in exon 12 of DKC1 gene of the patient,but not in other family members or normal individuals.DNA sequencing showed a 1236G→T transition in DKC1 gene in the pa- tient,which resulted in a 412W→C substitution in DKC1.No mutation was found in other family members and normal individuals.Conclusion The 1236G→T transition in the patient is a novel mutation in DKC1 gene,which could be a causative factor of dyskeratosis congenita.

A Case of Dyskeratosis Congenita / 대한피부과학회지

Dyskeratosis congsnita is a rare congenital disorder characterized by the triad of reticular pigmentation of the skin. dystrophic naila, and leukoplakia of the mucous membrane, and is often associated with severe pancytopenia. A 9-year-old boy had reticular pigmentation of the skin, dystropbic changes of the finger and toe nails, white patches of the buccal mucosa, mild hyperkeratosia of the palms and soles, excesaive lacrimation, dysphagia and severe pancytopenia, Bone marrow showed hypoplastic anemia and decreased cell mediated immunity was noticed.