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Hepatology (Baltimore, Md.) Dec 2023Dyskeratosis congenita (DC) and related telomere biology disorders (TBD) are characterized by very short telomeres and multisystem organ involvement including liver...
BACKGROUND AND AIMS
Dyskeratosis congenita (DC) and related telomere biology disorders (TBD) are characterized by very short telomeres and multisystem organ involvement including liver disease. Our study aimed to characterize baseline hepatic abnormalities in patients with DC/TBD and determine risk factors associated with liver disease progression.
APPROACH AND RESULTS
A retrospective review was performed on a cohort of 58 patients (39 males) with DC/TBD who were prospectively evaluated at a single institute from 2002 to 2019. The median age at initial assessment was 18 (1.4-67.6) years, and median follow-up duration was 6 (1.4-8.2) years. Patients with autosomal or X-linked recessive inheritance and those with heterozygous TINF2 DC were significantly younger, predominantly male, and more likely to have DC-associated mucocutaneous triad features and severe bone marrow failure compared with autosomal dominant-non- TINF2 DC/TBD patients. Liver abnormality (defined at baseline assessment by laboratory and/or radiological findings) was present in 72.4% of patients with predominantly cholestatic pattern of liver enzyme elevation. Clinically significant liver disease and portal hypertension developed in 17.2% of patients during the 6-year follow-up; this progression was mainly seen in patients with recessive or TINF2 -associated DC. Significant risk factors associated with progression included the presence of pulmonary or vascular disease.
CONCLUSIONS
Our experience shows a high prevalence of cholestatic pattern of liver abnormality with progression to portal hypertension in patients with DC/TBD. Presence of pulmonary and/or vascular disease in patients with recessive or TINF2 DC was an important predictor of liver disease progression, suggesting the need for increased vigilance and monitoring for complications in these patients.
Topics: Humans; Male; Female; Dyskeratosis Congenita; Digestive System Diseases; Telomere; Hypertension, Portal; Vascular Diseases; Disease Progression; Biology; Mutation; Telomerase
PubMed: 37184208
DOI: 10.1097/HEP.0000000000000461 -
Oxford Medical Case Reports May 2024Dyskeratosis congenita (DKC) is a rare genetic disorder characterized by lacy reticular skin hyperpigmentation, bone marrow failure, nail dystrophy, and oral...
Dyskeratosis congenita (DKC) is a rare genetic disorder characterized by lacy reticular skin hyperpigmentation, bone marrow failure, nail dystrophy, and oral leukoplakia. To the best of our knowledge, only around 200 cases were reported in the medical literature, and in this report, we present another distinctive case from Syria. This case report describes a male patient with generalized reticular pigmentation and abnormal nails since childhood. The patient reported a history of recurrent urethral stenosis and corneal density. Dermoscopic examination revealed pigmented lines arranged in a netlike pattern. Histopathological findings were nonspecific. Hematological values were unremarkable. A contrast CT scan revealed changes in the bladder wall. The final diagnosis of Dyskeratosis Congenita was made based on the clinical criteria. This disorder can present with additional cutaneous manifestations and systemic complications. Treatment are generally prescribed to maintain bone marrow function, based on the fact that it is the major cause of death. Regular monitoring and screening for associated conditions are recommended.
PubMed: 38784779
DOI: 10.1093/omcr/omae049 -
Blood Feb 2022
Topics: Biology; Dyskeratosis Congenita; Family; Humans; Telomere
PubMed: 35175322
DOI: 10.1182/blood.2021014533 -
Genes Mar 2022Dyskeratosis congenital (DC) is the first genetic syndrome described among telomeropathies. Its classical phenotype is characterized by the mucocutaneous triad of... (Review)
Review
Dyskeratosis congenital (DC) is the first genetic syndrome described among telomeropathies. Its classical phenotype is characterized by the mucocutaneous triad of reticulated pigmentation of skin lace, nail dystrophy and oral leukoplakia. The clinical presentation, however, is heterogeneous and serious clinical complications include bone marrow failure, hematological and solid tumors. It may also involve immunodeficiencies, dental, pulmonary and liver disorders, and other minor complication. Dyskeratosis congenita shows marked genetic heterogeneity, as at least 14 genes are responsible for the shortening of telomeres characteristic of this disease. This review discusses clinical characteristics, molecular genetics, disease evolution, available therapeutic options and differential diagnosis of dyskeratosis congenita to provide an interdisciplinary and personalized medical assessment that includes family genetic counseling.
Topics: Dyskeratosis Congenita; Humans; Leukoplakia, Oral; Nails, Malformed; Rare Diseases; Telomere
PubMed: 35328050
DOI: 10.3390/genes13030496 -
Frontiers in Pediatrics 2023Dyskeratosis congenita (DC) is a multisystem and ultra-rare hereditary disease characterized by somatic involvement, bone marrow failure, and predisposition to cancer....
BACKGROUND
Dyskeratosis congenita (DC) is a multisystem and ultra-rare hereditary disease characterized by somatic involvement, bone marrow failure, and predisposition to cancer. The main objective of this study is to describe the natural history of DC through a cohort of patients diagnosed in childhood and followed up for a long period of time.
MATERIAL AND METHODS
Multicenter, retrospective, longitudinal study conducted in patients followed up to 24 years since being diagnosed in childhood (between 1998 and 2020).
RESULTS
Fourteen patients were diagnosed with DC between the ages of 3 and 17 years (median, 8.5 years). They all had hematologic manifestations at diagnosis, and nine developed mucocutaneous manifestations during the first decade of life. Seven presented severe DC variants. All developed non-hematologic manifestations during follow-up. Mutations were identified in 12 patients. Thirteen progressed to bone marrow failure at a median age of 8 years [range, 3-18 years], and eight received a hematopoietic stem cell transplant. Median follow-up time was 9 years [range, 2-24 years]. Six patients died, the median age was 13 years [range, 6-24 years]. As of November 2022, eight patients were still alive, with a median age of 18 years [range, 6-32 years]. None of them have developed myeloblastic syndrome or cancer.
CONCLUSIONS
DC was associated with high morbidity and mortality in our series. Hematologic manifestations appeared early and consistently. Non-hematologic manifestations developed progressively. No patient developed cancer possibly due to their young age. Due to the complexity of the disease multidisciplinary follow-up and adequate transition to adult care are essential.
PubMed: 37593443
DOI: 10.3389/fped.2023.1182476 -
Cells Sep 2021In the human cornea, regeneration of the epithelium is regulated by the stem cell reservoir of the limbus, which is the marginal region of the cornea representing the... (Review)
Review
In the human cornea, regeneration of the epithelium is regulated by the stem cell reservoir of the limbus, which is the marginal region of the cornea representing the anatomical and functional border between the corneal and conjunctival epithelium. In support of this concept, extensive limbal damage, e.g., by chemical or thermal injury, inflammation, or surgery, may induce limbal stem cell deficiency (LSCD) leading to vascularization and opacification of the cornea and eventually vision loss. These acquired forms of limbal stem cell deficiency may occur uni- or bilaterally, which is important for the choice of treatment. Moreover, a variety of inherited diseases, such as congenital aniridia or dyskeratosis congenita, are characterized by LSCD typically occurring bilaterally. Several techniques of autologous and allogenic stem cell transplantation have been established. The limbus can be restored by transplantation of whole limbal grafts, small limbal biopsies or by ex vivo-expanded limbal cells. In this review, the physiology of the corneal epithelium, the pathophysiology of LSCD, and the therapeutic options will be presented.
Topics: Animals; Cornea; Corneal Diseases; Epithelial Cells; Epithelium, Corneal; Humans; Stem Cell Transplantation; Stem Cells
PubMed: 34571952
DOI: 10.3390/cells10092302 -
GeroScience Aug 2023Short telomeres are a defining feature of telomere biology disorders (TBDs), including dyskeratosis congenita (DC), for which there is no effective general cure....
Short telomeres are a defining feature of telomere biology disorders (TBDs), including dyskeratosis congenita (DC), for which there is no effective general cure. Patients with TBDs often experience bone marrow failure. NAD, an essential metabolic coenzyme, is decreased in models of DC. Herein, using telomerase reverse transcriptase null (Tert) mice with critically short telomeres, we investigated the effect of NAD supplementation with the NAD precursor, nicotinamide riboside (NR), on features of health span disrupted by telomere impairment. Our results revealed that NR ameliorated body weight loss in Tert mice and improved telomere integrity and telomere dysfunction-induced systemic inflammation. NR supplementation also mitigated myeloid skewing of Tert hematopoietic stem cells. Furthermore, NR alleviated villous atrophy and inflammation in the small intestine of Tert transplant recipient mice. Altogether, our findings support NAD intervention as a potential therapeutic strategy to enhance aspects of health span compromised by telomere attrition.
Topics: Humans; Animals; Mice; NAD; Telomere; Dyskeratosis Congenita; Inflammation; Hematopoietic Stem Cell Transplantation
PubMed: 36826621
DOI: 10.1007/s11357-023-00752-2 -
Medicina 2021Dyskeratosis congenita is a rare inheritable disease which causes peculiar dermatological features and bone marrow failure with an increased risk of severe infections...
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.
Topics: Brain Abscess; Dyskeratosis Congenita; Humans
PubMed: 34633962
DOI: No ID Found -
Medical Hypotheses Jun 2022Dyskeratosis Congenita (DC) is a rare and heterogeneous disease. This disorder is resulted from a defect in the telomere maintenance in stem cells. Telomerase RNA...
Dyskeratosis Congenita (DC) is a rare and heterogeneous disease. This disorder is resulted from a defect in the telomere maintenance in stem cells. Telomerase RNA component, shelterin complex, and telomerase reverse transcriptase are mutated in this disease. Many studies have previously confirmed shorter leukocyte telomere length in DC. On the other hand, the association between telomere length and Coronavirus disease 2019 (COVID-19) indicated that people with a short telomere background mostly show more severe symptoms related to COVID-19, and the mortality rate among them increases as well. Because patients with DC have an abnormally short telomere length, in the current study, we hypothesized that they are at higher risk of developing symptomatic COVID-19 that requires further clinical care.
PubMed: 35464998
DOI: 10.1016/j.mehy.2022.110843 -
Brain and Behavior May 2021This study aimed to summarize the magnetic resonance imaging (MRI) and computed tomography (CT) features of the central nervous system (CNS) in children with...
OBJECTIVE
This study aimed to summarize the magnetic resonance imaging (MRI) and computed tomography (CT) features of the central nervous system (CNS) in children with Hoyeraal-Hreidarsson syndrome.
METHODS
The imaging and clinical data of four children diagnosed with Hoyeraal-Hreidarsson syndrome by clinical and laboratory tests in the Guangzhou Women and Children's Medical Center were gathered and analyzed retrospectively. The clinical manifestations and CNS imaging features of Hoyeraal-Hreidarsson syndrome were summarized based on our results and a literature review.
RESULTS
Our results showed that delayed development, skin pigmentation, nail/toenail dystrophy, thrombocytopenia, and anemia are the most observed clinical presentations of Hoyeraal-Hreidarsson syndrome. Important findings on CNS imaging showed that all patients had cerebellar hypoplasia, delayed myelination, hydrocephalus, brain atrophy, and calcification. The gene mutations in all cases were consistent with those of dyskeratosis congenita, including TINF2 mutations in three cases and DKC1 mutations in one case.
CONCLUSION
Hoyeraal-Hreidarsson syndrome is a severe variant of dyskeratosis congenita. Both DKC1 and TINF2 mutations can lead to the phenotypes of Hoyeraal-Hreidarsson syndrome. In our study, CNS imaging revealed that cerebellar hypoplasia has an important diagnostic value for Hoyeraal-Hreidarsson syndrome while delayed myelination, calcification of the parenchyma, brain atrophy, and hydrocephalus are also important findings on CNS imaging. Combining imaging features with clinical and laboratory indicators can assist the diagnosis of Hoyeraal-Hreidarsson syndrome.
Topics: Brain; Cell Cycle Proteins; Child; Dyskeratosis Congenita; Female; Fetal Growth Retardation; Humans; Intellectual Disability; Microcephaly; Mutation; Neuroimaging; Nuclear Proteins; Retrospective Studies
PubMed: 33734615
DOI: 10.1002/brb3.2079