The typical clinical features consist of lacy reticular skin pigmentation, nail dystrophy and oral leukoplakia. Apr 12, 2010 dyskeratosis congenita dc is characterized by reticular skin pigmentation, oral leukoplakia and abnormal nails. Dyskeratosis congenita dc is an uncommon hereditary syndrome. What is dyskeratosis congenita dyskeratosis congenita is also known as zinsserengmancole syndrome. Dyskeratosis congenita dkc is a rare progressive boen marrow disorder associated with multi systemic involvement. Mild forms of dc can present with aplastic anaemia. Premature keratinization in individual epithelial cells that have not reached the keratinizing surface layer.
Dyskeratosis congenita induced cirrhosis for liver transplantation. It is also characterized by triad of abnormal skin pigmentation, nail dystrophy and mucosal leukoplakia. These syndromes vary in severity and can affect children and adults. Dyskeratosis congenita skin phenotype demonstrating characteristic reticular skin pigmentation. Bm failure is the principal cause of premature mortality. Dyskeratosis congenita nord national organization for. In the dkc registry, approximately 70% of affected individuals died of bone marrow failure or its complications, and these deaths occurred at a median age of 16 years. Hybridization screening with 28 candidate cdnas resulted in the detection of a. In its classic form, it is characterized by mucocutaneous abnormalities, bm failure, and a predisposition to cancer. Dyskeratosis congenita dc is an inherited bone marrow failure bmf syndrome characterized by the classic triad of abnormal skin pigmentation, nail dystrophy, and oral leukoplakia. Dyskeratosis congenita with a novel genetic variant in the.
Discussion dyskeratosis congenita is a rare multisystem disorder characterized by the triad of abnormal skin pigmentation, nail dystrophy and mucosal leucoplakia. The invitae dyskeratosis congenita panel analyzes genes associated with dyskeratosis congenita dc. Classic triad of this syndrome is skin pigmentation. Dyskeratosis congenita dc was the first tbd to be described. The patients had nail dystrophy, leukoplakia, bone marrow failure, severe bcell immunodeficiency, intrauterine growth retardation, growth retardation, microcephaly, cerebellar hypoplasia, and esophageal dysfunction. Pdf dyskeratosis congenita dc is an inherited bone marrow failure bmf syndrome characterized by the classic triad of abnormal skin pigmentation. Individuals with this congenital disorder often present with unusual skin conditions which indicate the disease, although in some cases, the first indication of dkc is bone marrow failure. In 10 patients from 7 families with severe autosomal recessive dyskeratosis congenita, walne et al. Pdf dyskeratosis congenita dkc is an inherited bone marrow failure bmf syndrome typified by reticulated skin pigmentation, nail.
Dyskeratosis congenita dc is an inherited bone marrow failure syndrome caused by defects in the telomere maintenance pathway. Dyskeratosis congenita with portal hypertension of unknown. People with dc are at increased risk for progressive bone marrow failure bmf, myelodysplastic syndrome mds or acute myelogenous leukemia. Dyskeratosis congenita with a novel genetic variant in the dkc1. Dceg investigators in the clinical genetics branch cgb showed that telomere length, as measured by flow cytometryfish was both sensitive and specific for distinguishing dc from healthy individuals and from those with other ibmfs. Patients with the classic forms of dc are usually diagnosed in childhood, and they have a triad of mucocutaneous features including dysplastic nails. A wide spectrum of features table 1 and figure 1 affecting every system in the body, particularly the bm, have.
Dyskeratosis congenita dc is a rare inherited bone marrow failure syndrome characterized by the triad of dystrophy of the nails 90%, reticular skin pigmentation 90%, and oral leukoplakia 80%. Patients with dc are more likely to develop deficiencies in red blood cells, white blood cells and platelets, leading to aplastic anemia, myelodysplastic syndrome, leukemia and other cancers. A cases reported in the literature through 2008, n 65. The condition, which makes up about 1 percent of all telomere syndromes, is. Dyskeratosis congenita is a rare form of bone marrow failure. In rare cases, a patients telomere syndrome may appear as a condition called dyskeratosis congenita. Sep 22, 2017 dyskeratosis congenita is a disorder that may affect many parts of the body. A 14yearold girl with dyskeratosis congenita dc was evaluated for. Dyskeratosis congenita is a rare skin and bone marrow failure syndrome caused by defective telomere maintenance in stem cells. Pubmed is a searchable database of medical literature and lists journal articles that discuss dyskeratosis congenita autosomal recessive. What is the life expectancy of someone with dyskeratosis.
Three features are especially characteristic of this disorder. Dyskeratosis congenita dkc,also known as zinsserengmancole syndrome is a rare progressive congenital disorder with a highly variable phenotype. Dyskeratosis congenita is a multisystem disorder caused by defective telomere maintenance. Dec 10, 2011 dyskeratosis congenita dc is a multisystem inherited syndrome exhibiting marked clinical and genetic heterogeneity. It is a group of genetic diseases that most commonly manifest with mucocutaneous signs, bone marrow failure andor lung or liver fibrosis there is considerable variability in the severity, age at onset and organ involvement, even within individual families. Transplantation in patients with dyskeratosis congenita, american society for blood and marrow transplantation. Bilateral proliferative retinopathy associated with. My son, lathyn, was born may 2014, was diagnosed with dyskeratosis congenita july 2015 and passed away from it september 2015.
People with dc are at increased risk for progressive bone marrow failure bmf, myelodysplastic syndrome mds or acute myelogenous. The subsets of dc include classic dc, hoyeraal hreidarsson syndrome hhs, revesz syndrome, dclike conditions and isolated subtypes. A wide spectrum of features table 1 and figure 1 affecting every system in the body, particularly the bm. Dyskeratosis congenita dc is a rare genetic disorder of bone marrow failure inherited in an xlinked, autosomal dominant or autosomal recessive pattern. Dc and related short telomere syndromes are caused by mutations that interfere with normal maintenance of telomeres, the regions at the ends of the chromosomes that protect nucleated cells from. B cases enrolled in the nci ibmfs dc cohort through 2007, n 11. Dyskeratosis congenita dc is a multisystem disorder which in its classical form is characterised by.
However, patients usually develop bmf and are predisposed to cancer, with increased risk for squamous cell carcinoma and hematolymphoid neoplasms. Our mission is to provide information and support services to families worldwide affected by dyskeratosis congenita and telomere biology disorders, to encourage the medical communitys research in finding causes and effective treatments, and to facilitate improved diagnosis by educating medical providers. Xlinked dyskeratosis congenita is caused by mutations in a. Dyskeratosis congenita dkc, also known as zinsserengmancole syndrome, is a rare, progressive bone marrow failure syndrome characterized by the triad of reticulated skin hyperpigmentation, nail dystrophy, and oral leukoplakia.
Xlinked dyskeratosis congenita is caused by mutations in. He j, et al, targeted disruption of dkc1, the gene mutated in xlinked dyskeratosis congenital causes embryonic lethality. Dyskeratosis congenita dc is a rare condition classified under a broad spectrum of genetic disorders known as telomere diseases. Wed like to understand how you use our websites in order to improve them. The dkc1 gene is located on the x chromosome, which is one of the two sex chromosomes. Dyskeratosis congenita dc is characterized by reticular skin pigmentation, oral leukoplakia and abnormal nails. Jan 27, 2020 dyskeratosis congenita dkc, also known as zinsserengmancole syndrome, is a rare, progressive bone marrow failure syndrome characterized by the triad of reticulated skin hyperpigmentation, nail dystrophy, and oral leukoplakia.
Patients with dc have varied clinical presentations, which may include the. Dyskeratosis congenita dc is an inherited disorder characterized by bone marrow failure, cancer predisposition, and additional somatic abnormalities. Hematopoietic stem cell transplantation hsct can cure the bone marrow failure, but it does not eliminate the risks of other complications, for which lifelong. The case reported is the first in a negro and showed the previously unrecorded abnormalities.
These diseases can often cause bone marrow failure and lung disease. Stem cells, telomerase and dyskeratosis congenita mason. Dyskeratosis congenita study national cancer institute. Dyskeratosis congenita autosomal recessive genetic and. Patients with dc have very short telomeres and approximately onehalf have. It is associated with a high risk of developing aplastic anemia.
Features are variable and include bone marrow failure, pulmonary and liver fibrosis, and premature graying of the hair summary by armanios et al. These telomeropathies also include hoyeraalhreidarsson syndrome hh and revesz syndrome, which are severe forms of dyskeratosis congenita, as well as a subset of idiopathic pulmonary fibrosis, aplastic anemia. In truth, dc is a highly heterogeneous disorder that is difficult to. Cumulative survival in cases with dyskeratosis congenita after bone marrow transplantation, calculated using the method of kaplan and meier. Click on the link to view a sample search on this topic. In males who have only one x chromosome, one altered copy of the gene in each cell is sufficient to cause the condition. Dyskeratosis congenita or zinssercoleengman syndromeis is a rare inherited bone marrow failure syndrome ibmfs characterized by diagnostic triad of reticulated skin hyperpigmentation, nail dystrophy, and oromucosal leukoplakia 1. It is a group of genetic diseases that most commonly manifest with mucocutaneous signs, bone marrow failure andor lung or liver fibrosis. Pdf the diagnosis and treatment of dyskeratosis congenita.
Abstract dyskeratosis congenita dc is the prototypical member of a family of diseases caused by defective telomere maintenance. Dyskeratosis congenita can have different inheritance patterns. Dyskeratosis congenita an overview sciencedirect topics. Dyskeratosis congenita dc is a progressive, multisystem, inherited disorder of telomere biology with high risks of morbidity and mortality from bone marrow failure, hematologic malignancy, solid tumors and pulmonary fibrosis. Diseasespecific hematopoietic cell transplantation. First described as a discrete syndrome in 1910 1, dyskeratosis congenita dc is a disease that can. Pdf clinical and genetic features of dyskeratosis congenita. Dyskeratosis congenita is a rare genetic form of bone marrow failure, the inability of the marrow to produce sufficient blood cells. Xlinked recessive dyskeratosis congenita dkc is a rare bonemarrow failure disorder linked to xq28. Dyskeratosis congenita and telomere disorders panel disorder. His symptoms started at around 6 months which was a developmental delay, so he had an mri done that showed he had vanishing. Vulliamy tj, et al, mutations in dyskeratosis congenita, blood 107.
First described as a discrete syndrome in 1910, dyskeratosis congenita dc is a disease that can be pigeonholed into a number of alternative classifications including premature aging syndrome, bone marrow failure syndrome and cancer predisposition syndrome, amongst others. Images in clinical medicine from the new england journal of medicine dyskeratosis congenita. The classic triad may not be present in all individuals. Aplastic anaemia aa, dyskeratosis congenita dc, dyskerin, hoyeraalhreidarsson syndrome hh, telomerase name of the diseaseincluded diseases dyskeratosis congenital is also known as zinsserengmancole syndrome. The prevalence of dc is estimated to be 1 in 1,000,000. The initial mutations were identified by exome sequencing of 1 family. Dyskeratosis congenita nord national organization for rare. Dyskeratosis congenita, stem cells and telomeres sciencedirect. Cancer in dyskeratosis congenita blood american society.
Dyskeratosis congenita induced cirrhosis for liver. The spectrum of diseases encompassed by the term dyskeratosis congenita dc has expanded considerably since its initial description in 1910. Patients with dc are more likely to develop deficiencies in red blood cells, white blood cells and platelets, leading to aplastic anemia, myelodysplastic syndrome, leukemia and. It is a multisystem disorder which is heterogeneous at the genetic and clinical levels. Evidence exists for telomerase dysfunction, ribosome deficiency, and protein synthesis dysfunction in this disorder. The entity was classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, but these components do not always occur. Dyskeratosis definition of dyskeratosis by medical. Dyskeratosis congenita dc is an xlinked recessive trait which is characterized by bone marrow failure and a triad of mucosal leukoplakia, nail dystrophy, and. It has a wide array of clinical features and patients may be cared for by many medical sub specialties. When dyskeratosis congenita is caused by dkc1 gene mutations, it is inherited in an xlinked recessive pattern.
Dyskeratosis congenita hematology american society of. Pdf dyskeratosis congenita, stem cells and telomeres. Dyskeratosis congenita is a disorder that may affect many parts of the body. Team telomere a community for telomere biology disorders.
First described in the medical literature in 1906, dyskeratosis congenita was originally thought to be a. Dc is a clinically and genetically heterogeneous telomere disorder characterized by abnormal skin pigmentation, nail dystrophy, oral leukoplakia and increased risk of progressive bone marrow failure and malignancies. Dyskeratosis congenita genetics home reference nih. Vulliamy tj, et al, the rna component of telomerase is mutated in autosomal dominant dyskeratosis congenital, 2001, nature 4. Dkc1, tinf2, terc and tert gene analysis in dyskeratosis. Dyskeratosis congenita can have different inheritance patterns when dyskeratosis congenita is caused by dkc1 gene mutations, it is inherited in an xlinked recessive pattern. The diagnosis and treatment of dyskeratosis congenita. Download article pdf view full text htmlmachine readable. Dyskeratosis congenita, also known as dkc or dc, is a rare genetic disorder that causes bone marrow failure. Dyskeratosis congenita and telomere disorders panel. Dyskeratosis congenita dc, a telomere biology disorder, is characterized by a classic triad of dysplastic nails, lacy reticular pigmentation of the upper chest andor neck, and oral leukoplakia. Hybridization screening with 28 candidate cdnas resulted in the detection of a 3. The hoyeraalhreidarsson syndrome is a severe variant of dc. Dyskeratosis congenita jama dermatology jama network.
Our mission a community of telomere biology disorders. Dyskeratosis is latin and means the irreversible degeneration of skin tissue, and congenita means inborn. A number of mutations in genes coding for proteins that function to. Dyskeratosis congenita is also known as zinsserengmancole syndrome. It is a genetic disorder that also affects skin, nails and mucosa. Dyskeratosis congenita dc is a rare, inherited, skin and bone marrow failure disease. Dyskeratosis definition of dyskeratosis by medical dictionary.
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