A male infant was found to have bilateral exudative retinopathy at 6 months of age. A month later severe aplastic anaemia was diagnosed, eventually leading to the infant's death. Additional features of this seemingly new syndrome were intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia because of cerebellar hypoplasia, cerebral calcifications, extensor hypertonia, and progressive psychomotor retardation.
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... Revesz syndrome (OMIM #268130) was described for the first time in 1992 . It is another infrequent variant of DC due to pathogenic variants in the TINF2 gene . ...
... The representing symptoms are the presence of bilateral exudative retinopathy, which is associated in most cases with intracranial calcification, and the classic alterations of DC, such as early bone marrow failure  and mucocutaneous disease. Intrauterine growth retardation, cerebellar hypoplasia and developmental delay may also be present . ...
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.
... Some cases of HHS associated with abnormalities of the eye like bilateral exudative retinopathy and Coats retinopathy; named as Revesz syndrome. 11 The boy also had eye abnormality-white eye reflex of right eye, Though genetic confirmation was not possible; classic clinical features of early onset of disease with ectodermal changes of nails, oral leukoplakia, marrow failure, microcephaly, brain abnormality, eye abnormality with negative TORCH matches with severe form of DC-HHS/Revesz syndrome. ...
Dyskeratosis congenita is a rare type of inherited bone marrow failure syndromes
(IBMFs) characterized by ectodermal dysplasia, bone marrow failure and cancer
predisposition. Accelerated telomere shortening is supposed to be the causal
mechanism of this disease. Features of ectodermal dysplasia appears early and
may give clues of suspicion of forthcoming bone marrow disease. It has variable
presentation and severe form of disease presents earlier. This a case report on a 2
year 2-month old boy who presented with features of bone marrow failure and had
abnormality of skin, nail and oral mucosa.
Key word: Dyskeratosis congenita (DC
... In addition, exudative retinopathy, intracranial calcifications, and cerebellar hypoplasia are commonly present. 1,4,5 The retinal features include avascular areas in the peripheral retina with telangiectatic vessels, arterio-venous anastomotic loops, neovascularizations, retinal exudates, and exudative and/or tractional retinal detachments. 3,6-9 So far, six cases of Revesz syndrome that underwent ocular treatments for the retinal complications have been reported. ...
Revesz syndrome is a rare type of the dyskeratosis congenita spectrum disorder that is characterized by nail dystrophy, oral leukoplakia, and abnormal skin pigmentation. The retinal features are similar to those of exudative retinopathy with avascular areas of the peripheral retina. There are only a few publications describing patients with Revesz syndrome who underwent ocular treatments for the retinal complications. We report a Case of Revesz syndrome with bilateral retinal detachments that were successfully reattached by pars plana vitrectomy.
A 3-year-old Japanese girl with Revesz Syndrome had progressive vitreal hemorrhages and tractional retinal detachments in both eyes. She underwent pars plana vitrectomy with lensectomy on both eyes. A retinal attachment with vision improvement was achieved by a single surgery for the right eye and after repeated surgeries for the left eye. Postoperative electroretinographic (ERG) examinations of the right eye showed a negative type ERG with the b-wave/a-wave ratio <1.0. There were extensive areas of avascular retina detected by fluorescein angiography and a thinning of the inner and outer retina detected by optical coherence tomography.
Conclusion and importance
Pars plana vitrectomy can effectively treat the extensive retinal detachment in an eye with Revesz syndrome. However, postoperative retinal ischemia can be detected by careful imaging.
... This resembles Revesz but cerebellar and hematologic manifestations are less prominent. It is due to compound heterozygous mutations in CTC1 . ...
Revesz syndrome is a rare telomeropathy characterized by bone marrow failure and exudative retinopathy. We report the case of a 2-year-old male child, initially treated with bilateral laser photocoagulation for retinopathy of prematurity. He developed exudative changes in the right eye, presumed to be Coats disease. Later, the left eye developed a total vitreous hemorrhage. Proliferative retinopathy was noted intraoperatively. Systemic features of bone marrow failure, growth retardation, and nail pigmentation were present. Genetic testing confirmed the diagnosis of Revesz syndrome. We describe our approach to diagnosis and surgical management of the case. [Ophthalmic Surg Lasers Imaging Retina 2022;53(6): 346-348.].
The inherited bone marrow failure syndromes (IBMFS) are a clinically and molecularly heterogeneous group of cancer-prone disorders. Many IBMFS are associated with specific clinical characteristics and/or dysmorphic features. The IBMFS associated with increased risk of leukemia, myelodysplastic syndrome (MDS), and certain solid tumors include Fanconi anemia, dyskeratosis congenita, and Diamond Blackfan anemia. Individuals with Shwachman Diamond syndrome, severe congenital neutropenia, congenital amegakaryocytic thrombocytopenia, or thrombocytopenia absent radius syndrome may be at increased risk of leukemia. Patients with IBMFS have syndrome-specific pathogenic germline variants in genes critical in DNA repair, telomere biology, ribosome biology, or hematopoiesis.
To determine the clinical characteristics of patients and family members with familial exudative vitreoretinopathy (FEVR) caused by mutations in the KIF11 gene.
Twenty-one patients from 10 FEVR families with mutations in the KIF11 gene were studied. The retinal and systemic features were examined. The genetic analyses performed included Sanger sequencing of the KIF11 gene, whole exome sequencing, as well as array comparative genomic hybridization (CGH) analysis and multiple ligation probe assay (MLPA).
Sequence analysis revealed seven different KIF11 mutations. Array CGH with MLPA revealed two different exon deletions. All probands had advanced FEVR with retinal detachments (RDs) and microcephaly with or without developmental disabilities. Patients with bilateral RDs were more frequently associated with developmental disabilities (P = 0.023). Multimodal imaging of the family members revealed that six of nine patients without RDs (66%) had varying degrees of chorioretinopathy. The retinal folds in FEVR patients were associated with severe retinal avascularization. However, funduscopic changes in the peripheral retina were unremarkable in family members without RDs. A score representing the peripheral vascular anomalies determined from the fluorescein angiograms was lower than that of control eyes of patients with mutations of the Wnt signaling genes (P = 0.0029).
The probands with KIF11 mutations were associated with severe ocular and systemic pathologies, whereas affected family members showed highly variable clinical manifestations. Peripheral vascular anomalies can often be unremarkable in eyes without RDs.
These findings highlight more diverse mechanisms that underlie the pathological changes in patients with FEVR.
In this chapter, we describe the advances in molecular biology methods and discuss how current methods address the highly heterogeneous nature of human genomic variation. We start presenting a historical perspective of early developments that culminated in our knowledge of human genomes’ enormous diversity. Next, we propose a classification of variants according to these criteria: variant’s length, frequency, and consequence. Variant’s length is critical when choosing between two main groups of methods: fragment-based or sequence-based. We explore these two groups in Sect. 3.3. Two other divisions were considered to describe the methods: if they are targeted or genome-wide approaches and if they focus on common or rare variants. Fluorescence in-situ hybridization (FISH), array comparative genomic hybridization (array-CGH), multiplex ligation-dependent probe amplification (MLPA), and triplet repeat primed PCR (TP-PCR) are discussed in the section of fragment-based methods. Sanger sequencing, genotyping microarrays, and a detailed description of next-generation sequencing are covered in the sequence-based section. In Sect. 3.4, we discuss current applications, including a brief workflow for molecular diagnosis, rare-variant association testing, and polygenic risk scores. Finally, Sect. 3.5 explores perspectives and presents a glimpse of promising methods, such as Cell-free DNA, long-read sequencing, and integrative approaches with other ‘omics’. Although it is still difficult to interrogate the full spectrum of human genome variation using a single method, advances might soon overcome these challenges.
Transposable elements (TEs) are sequences capable of “jumping” from one point to another in our DNA through different mechanisms. These genetic elements make up most of our genome and through the evolutionary time, they have been co-opted as a valuable resource to be part of the host regulatory network, given rise to transcription factor binding sites, enhancers, non-coding RNAs, and others. On the other hand, untamed and active elements that evade controlling cellular mechanisms can have a detrimental impact on cellular homeostasis. Studies have shown that TEs are implicated in the pathogenesis of various diseases, including cancer. In this case, their activity can result in somatically acquired insertions, which may cause driver mutations and genomic instability, resulting in a variety of alterations associated with the cancer hallmarks such as immortalization, immune evasion, inflammation, and metastasis, among others. In this chapter, we discuss the diversity and regulation of transposable elements, their impact in our genome, and delve into how their expression can promote tumor progression, impact cancer treatment response, and their possible uses in cancer precision medicine.
A large family with dyskeratosis congenita is reported. There were nine affected males, the findings in five of who are reported. We review 46 cases selected from the literature. The cardinal findings of this inherited multisystem disorder are delineated from these 51 cases. The complications of the disease, including opportunistic infection, are described. The parallel is made between dyskeratosis congenita and Fanconi's anaemia. The X-linked transmission of dyskeratosis congenita is confirmed by the family pedigree in this report. From the analysis of the families reported in the literature, there appears to be genetic heterogeneity in this disease. This study in our family indicates absence of close linkage between the Xga locus and the X-linked recessive form of dyskeratosis congenita.
We describe two sisters who have bilateral Coats reaction of the retina, intracranial calcification, sparse hair and dysplastic nails. The younger sibling has in addition distinct retinal angiomas in one eye. This combination of clinical findings has not been reported previously and is probably due to an autosomal recessive gene defect. Laser photocoagulation and cryotherapy has preserved good function in one eye of each child.
A case of dyskeratosis congenita (DC) with pancytopenia was studied in an attempt to elucidate the cause of the hypocellular bone marrow and pancytopenia. Levels of erythroid hemopoietic stem cells were estimated by clonal cell culture. Results showed a decrease in the number of precursor cells in both the bone marrow and the peripheral blood of this patient.