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Dyskeratosis Congenita

Karla Schmitt, Fabian Beier, Jens Panse, Tim H Brümmendorf
Telomere syndromes (syn. Telomeropathies) are inherited disorders hallmarked by accelerated telomere shortening based on a molecular defect within the telomerase/telomere complex. The rare, but well-defined model disorder Dyskeratosis congenita (DKC) characterized by typical skin manifestations and bone marrow failure represents the classical manifestation of telomere syndromes in childhood and adolescence. However, cryptic variants of DKC, clinically manifest through appearance of atypical bone marrow failure, lung fibrosis or liver cirrhosis - especially in adults up to the fifth decade of age - are frequently underdiagnosed...
October 2016: Deutsche Medizinische Wochenschrift
Aristomenis Thanos, Bozho Todorich, Stephen M Hypes, Yoshihiro Yonekawa, Benjamin Thomas, Sandeep Randhawa, Kimberly A Drenser, Michael T Trese
PURPOSE: To report a novel presentation of dyskeratosis congenita masquerading as familial exudative vitreoretinopathy. METHODS: Observational case series involving single family and literature review. RESULTS: A brother and sister were diagnosed with familial exudative vitreoretinopathy at ages 4 and 2, respectively. Both patients were managed with laser photocoagulation. Eight years after the initial presentation, both siblings developed pancytopenia secondary to bone marrow failure...
September 28, 2016: Retinal Cases & Brief Reports
Nieves Perdigones, Juan C Perin, Irene Schiano, Peter Nicholas, Jaclyn A Biegel, Philip J Mason, Daria V Babushok, Monica Bessler
Dyskeratosis congenita (DC) is a rare inherited telomeropathy most frequently caused by mutations in a number of genes all thought to be involved in telomere maintenance. The main causes of mortality in DC are bone marrow failure as well as malignancies including leukemias and solid tumors. The clinical picture including the degree of bone marrow failure, is highly variable and factors that contribute to this variability are poorly understood. Based on the recent finding of frequent clonal hematopoiesis in related bone marrow failure syndromes, we hypothesized that somatic mutations may also occur in DC and may contribute at least in part to the variability in blood production...
September 13, 2016: American Journal of Hematology
Amanda J Walne, Laura Collopy, Shirleny Cardoso, Alicia Ellison, Vincent Plagnol, Canan Albayrak, Davut Albayrak, Sara Sebnem Kilic, Turkan Patıroglu, Haluk Akar, Keith Godfrey, Tina Carter, Makia Marafie, Ajay Vora, Mikael Sundin, Thomas Vulliamy, Hemanth Tummala, Inderjeet Dokal
Dyskeratosis congenita is a highly pleotropic genetic disorder. This heterogeneity can lead to difficulties in making an accurate diagnosis and delays in appropriate management. The aim of this study was to determine the underlying genetic basis in patients presenting with features of dyskeratosis congenita and who were negative for mutations in the classical dyskeratosis congenita genes. By whole exome and targeted sequencing, we identified biallelic variants in genes that are not associated with dyskeratosis congenita in 17 individuals from 12 families...
October 2016: Haematologica
Shaimaa Elmahadi, Hideki Muramatsu, Seiji Kojima
PURPOSE OF REVIEW: Dyskeratosis congenita is an inherited bone marrow failure syndrome caused by defects in telomere maintenance. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for bone marrow failure because of dyskeratosis congenita. The present review summarizes the literature with respect to the diagnosis and treatment of patients with dyskeratosis congenita who received HSCT, and discusses the recent progress in the management of dyskeratosis congenita...
November 2016: Current Opinion in Hematology
Jialin Xu, Payal P Khincha, Neelam Giri, Blanche P Alter, Sharon A Savage, Judy M Y Wong
Dyskeratosis congenita (DC) is an inherited bone marrow failure and cancer susceptibility syndrome caused by germline mutations in telomere biology genes. Germline mutations in DKC1, which encodes the protein dyskerin, cause X-linked recessive DC. Due to skewed X-chromosome inactivation, female DKC1 mutation carriers do not typically develop clinical features of DC. This study evaluated female DKC1 mutation carriers with DC-associated phenotypes to elucidate the molecular features of their mutations, in comparison with unaffected carriers and mutation-negative female controls...
August 29, 2016: American Journal of Hematology
Kalpana Gupta, Swati Tripathi, Nidheesh Agarwal, Anurag Bareth
Dyskeratosiscongenita (DKC) is a genetically heterogeneous disease of defective telomere maintenance that may demonstrate different patterns of inheritance. It is characterized by thetriad of dystrophy of the nails, leukokeratosis of the oral mucosa, and extensive net-like pigmentation of the skin. We report a case ofDKC who presented with a chief complaint of dysphagia.
July 2016: Indian Dermatology Online Journal
Dong-Hun Woo, Qijun Chen, Ting-Lin B Yang, M Rebecca Glineburg, Carla Hoge, Nicolae A Leu, F Brad Johnson, Christopher J Lengner
Patients with dyskeratosis congenita (DC) suffer from stem cell failure in highly proliferative tissues, including the intestinal epithelium. Few therapeutic options exist for this disorder, and patients are treated primarily with bone marrow transplantation to restore hematopoietic function. Here, we generate isogenic DC patient and disease allele-corrected intestinal tissue using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated gene correction in induced pluripotent stem cells and directed differentiation...
September 1, 2016: Cell Stem Cell
Chaitanya Penmatsa, Sharada Reddy Jampanapalli, Sushma Bezawada, Uday Kumar Chowdary Birapu, Vasantha Kumari Radharapu
Zinsser-Cole-Engmann syndrome also called Dyskeratosis Congenita (DKC) is a rare genodermatosis first described by Zinsser in 1906. Mutations in DKC1 gene is responsible for DKC. It is usually inherited as an X-linked recessive trait, resulting in a striking male predilection. It is characterized by a triad of reticular skin pigmentation, nail dystrophy and mucosal leukoplakia. Complications include predisposition to malignancy and bone marrow failure. Here, we report a case of DKC in a 9-year-old boy with classic triad of signs...
June 2016: Journal of Clinical and Diagnostic Research: JCDR
Etsuro Ito, Tsutomu Toki, Kiminori Terui
Inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders characterized by bone marrow failure, congenital anomalies, and an increased risk of malignancies. Diagnosis is often difficult due to the wide variety of clinical expressions. The representative diseases are Diamond Blackfan anemia (DBA), Fanconi anemia (FA), congenital sideroblastic anemia (CSA), congenital dyserhthropoietic anemia, Shwachman Diamond syndrome, and dyskeratosis congenita. Next-generation sequencing technologies have facilitated the discovery of germline mutations that cause IBMFS...
July 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Shahinaz M Gadalla, Payal P Khincha, Hormuzd A Katki, Neelam Giri, Jason Y Y Wong, Stephen Spellman, Jack A Yanovski, Joan C Han, Immaculata De Vivo, Blanche P Alter, Sharon A Savage
BACKGROUND: Telomere length <1st percentile-for-age in leukocyte subsets by flow cytometry with fluorescence in situ hybridization (flow FISH) is highly sensitive and specific in diagnosing patients with dyskeratosis congenita (DC), a telomere biology disorder. METHODS: We evaluated the clinical utility of the high-throughput quantitative real-time PCR (qPCR) relative telomere length (RTL) measurement as a diagnostic test for DC in patients with a priori clinical and/or genetic DC diagnoses...
July 2016: Molecular Genetics & Genomic Medicine
Adedoyin Kalejaiye, Neelam Giri, Carmen C Brewer, Christopher K Zalewski, Kelly A King, Charleen D Adams, Philip S Rosenberg, H Jeffrey Kim, Blanche P Alter
BACKGROUND: The inherited bone marrow failure syndromes (IBMFSs) are diverse disorders with syndrome-specific features; their otologic and audiologic manifestations have not been well described. Our objective was to characterize these in patients with Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS), and to determine the association between physical findings and hearing loss. METHODS: Patients with an IBMFS underwent comprehensive clinical and laboratory evaluations and testing for syndrome-specific gene mutations...
July 18, 2016: Pediatric Blood & Cancer
Mukand Lal, Manoj Thakur, Sandeep Kashyap
Avascular necrosis of head of femur is a rare presentation in Dyskeratosis Congenita (DC). Aplastic anaemia, increased susceptibility to infections and fatal pulmonary complications often complicate the clinical scenario in these patients leading to short life span and difficulty in performing surgical interventions. The diagnosis initially and subsequent management by total hip replacement posed a great challenge. To our knowledge this is the first case report of any intervention in form of total hip Arthroplasty done in DC...
June 2016: Indian Journal of Hematology & Blood Transfusion
Nilufer Ozdemir Kutbay, Banu Sarer Yurekli, Zehra Erdemir, Emin Karaca, Idil Unal, Banu Yaman, Ferda Ozkinay, Fusun Saygili
No abstract text is available yet for this article.
April 2016: Hormones: International Journal of Endocrinology and Metabolism
Sarah A Bannon, Courtney D DiNardo
Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SBS), hallmarked by clinically-recognizable phenotypes (e...
2016: International Journal of Molecular Sciences
Aude-Annick Suter, Peter Itin, Karl Heinimann, Munaza Ahmed, Tazeen Ashraf, Helen Fryssira, Usha Kini, Pablo Lapunzina, Peter Miny, Mette Sommerlund, Mohnish Suri, Signe Vaeth, Pradeep Vasudevan, Sabina Gallati
BACKGROUND: Poikiloderma is defined as a chronic skin condition presenting with a combination of punctate atrophy, areas of depigmentation, hyperpigmentation and telangiectasia. In a variety of hereditary syndromes such as Rothmund-Thomson syndrome (RTS), Clericuzio-type poikiloderma with neutropenia (PN) and Dyskeratosis Congenita (DC), poikiloderma occurs as one of the main symptoms. Here, we report on genotype and phenotype data of a cohort of 44 index patients with RTS or related genodermatoses...
May 2016: Molecular Genetics & Genomic Medicine
Courtney D DiNardo, Sarah A Bannon, Mark Routbort, Anna Franklin, Maureen Mork, Mary Armanios, Emily M Mace, Jordan S Orange, Meselle Jeff-Eke, Jane E Churpek, Koichi Takahashi, Jeffrey L Jorgensen, Guillermo Garcia-Manero, Steve Kornblau, Alison Bertuch, Hannah Cheung, Kapil Bhalla, Andrew Futreal, Lucy A Godley, Keyur P Patel
INTRODUCTION: Although multiple predispositions to hematologic malignancies exist, evaluations for hereditary cancer syndromes (HCS) are underperformed by most hematologist/oncologists. Criteria for initiating HCS evaluation are poorly defined, and results of genetic testing for hereditary hematologic malignancies have not been systematically reported. PATIENTS AND METHODS: From April 2014 to August 2015, 67 patients were referred to the Hereditary Hematologic Malignancy Clinic (HHMC)...
July 2016: Clinical Lymphoma, Myeloma & Leukemia
Amha Gebremedhin, Ashenafi Bekele
Dyskeratosis congenita (DKC) is a rare, progressive bone marrow failure syndrome that is characterized by the triad of reticulated skin pigmentation, nail dystrophy and oral leukoplakia. Current evidence indicates that DKC is a disease of defective telomere maintenance, ribosome deficiency and protein synthesis dysfunction. Mortality is often associated with bone marrow failure (BMF), development of malignancy and other multisystem complications of the disease. Here we report two Ethiopian brothers with classical signs and symptoms of DKC...
October 2015: Ethiopian Medical Journal
Morgan Jones, Kamlesh Bisht, Sharon A Savage, Jayakrishnan Nandakumar, Catherine E Keegan, Ivan Maillard
Mammalian chromosomes terminate in stretches of repetitive telomeric DNA that act as buffers to avoid loss of essential genetic information during end-replication. A multiprotein complex known as shelterin prevents recognition of telomeric sequences as sites of DNA damage. Telomere erosion contributes to human diseases ranging from BM failure to premature aging syndromes and cancer. The role of shelterin telomere protection is less understood. Mutations in genes encoding the shelterin proteins TRF1-interacting nuclear factor 2 (TIN2) and adrenocortical dysplasia homolog (ACD) were identified in dyskeratosis congenita, a syndrome characterized by somatic stem cell dysfunction in multiple organs leading to BM failure and other pleiotropic manifestations...
May 2, 2016: Journal of Clinical Investigation
Michael J Allingham
Dyskeratosis congenita (DC) is the prototypical member of a family of diseases caused by defective telomere maintenance. These "telomeropathies" also include Hoyeraal-Hreidarsson syndrome (HH) and Revesz syndrome, which are severe forms of dyskeratosis congenita, as well as a subset of idiopathic pulmonary fibrosis, aplastic anemia, and Coats' plus syndrome. Retinopathy has only rarely been reported in DC and HH, but is universally present in Coats' plus and Revesz syndromes. The care of these patients is typically a multidisciplinary effort, and this should include monitoring by an ophthalmologist...
April 1, 2016: Ophthalmic Surgery, Lasers & Imaging Retina
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