Revesz syndrome (RS) is a rare genetic condition that is considered a variant of dyskeratosis congenita (DC). RS can present with a range of symptoms often including dysplastic nails, oral leukoplakia, and abnormal skin pigmentation, which are characteristic of DC.
Presentation
Revesz syndrome (RS) is a rare genetic disease. It is generally regarded in literature as a less commonly occurring, more severe, variant of dyskeratosis congenita (DC). Thus the former exhibit features that are typical of DC, such as abnormal nail formation, skin hyperpigmentation, and oral leukoplakia [1]. RS occurs as a result of genetic mutation, specifically in the TINF2 gene coding for a protein that is involved in telomere synthesis. The same gene has been found to be responsible for some forms of DC.
The phenotypic features of RS have not been fully delineated, as there is a small number of reported cases, amongst which there is great variation in clinical presentation [2] [3].
Features that are typical of RS include ocular and periorbital abnormalities such as lid deformities, exudative retinopathy, vitreous hemorrhage, corneal or vitreous opacification, and conjunctival scarring. These features manifest in childhood and may cause a decrease in visual acuity, or blindness. Within the central nervous system (CNS), patients with RS often show a hypoplastic cerebellum and cerebral calcifications. Some patients may present with ataxia [4].
Affected individuals have a high risk of developing malignant tumors and bone marrow failure. The latter may result in neutropenia, pancytopenia, and aplastic anemia, frequently appearing early in life. Additional features of RS include sparse hair, psychomotor retardation, and intrauterine growth restriction [5] [6].
Entire Body System
- Developmental Delay
Medical Term Other Names Description Global developmental delay Psychomotor developmental delay, Psychomotor retardation, Developmental delay, Lack of psychomotor development, Cognitive delay, Delayed intellectual development, Delayed milestones, Psychomotor [rarediseases.oscar.ncsu.edu]
delay sparse and fine hair) in conjunction with bilateral exudative retinopathy, and intracranial calcifications. [orpha.net]
Genes related to Revesz Syndrome TINF2 View recommended genes panels Clinical Features Top most frequent phenotypes and symptoms related to Revesz Syndrome Global developmental delay Ataxia Growth delay Nystagmus Anemia Intrauterine growth retardation [mendelian.co]
- Fatigue
The signs and symptoms of AML vary but may include easy bruising; bone pain or tenderness; fatigue; fever; frequent nosebleeds; bleeding from the gums; shortness of breath; … Eosinophilic Granulomatosis With Polyangiitis (EPGA) January 17, 2019 by Peter [checkrare.com]
For example, Social Security has issued rulings stating that that chronic fatigue syndrome, post-polio sydrome and fibromyalgia can satisfy the requirement for a medically determinable impairment. The rulings set forth criteria for those diagnoses. [swaniganlaw.com]
Some deaths are caused from Cachexia, also known as Wasting Syndrome, which manifests itself as loss of weight, muscle atrophy, fatigue, weakness and significant loss of appetite. [maria-online.com]
- Poor Growth
Symptoms of Hoyeraal Hreidarsson syndrome include poor growth of the child during pregnancy, head size that is smaller than expected (microcephaly), the back of the brain is not fully formed (cerebellar hypoplasia), a poor immune system, failure of bone [diseaseinfosearch.org]
Analysis of TIN2 protein in Patient 3's skin fibroblasts was not possible because of poor growth of the culture Plasmids TINF2 short isoform cDNA sequence derived from pLPC-N-FH2-TIN2 plasmid ( 17 ) (kindly provided by Titia De Lange, Rockefeller University [ncbi.nlm.nih.gov]
Hematological
- Easy Bruising
The signs and symptoms of AML vary but may include easy bruising; bone pain or tenderness; fatigue; fever; frequent nosebleeds; bleeding from the gums; shortness of breath; … Eosinophilic Granulomatosis With Polyangiitis (EPGA) January 17, 2019 by Peter [checkrare.com]
Eyes
- Strabismus
Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. All rights reserved. [ncbi.nlm.nih.gov]
Vitreous hemorrhage led to diminished vision and subsequent strabismus. [scielo.br]
- Vitreous Floaters
Fundoscopy of the right eye revealed preretinal hemorrhage, coarse vitreous floaters, and no signs of disruption. The left eye exhibited a previous diffuse vitreous hemorrhage and vitreous floaters. [scielo.br]
Skin
- Sparse Hair
【關鍵詞】 revesz syndrome retinitis pigmentosa retinal detachment bone marrow failure syndromes revesz syndrome is a rare congenital disorder characterized by intrauterine growth retardation, fine sparse hair, reticulate skin pigmentation, bone marrow failure [doc.qkzz.net]
Other features of this syndrome include intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia because of cerebellar hypoplasia, cerebral calcifications, extensor hypertonia, and progressive psychomotor retardation [cags.org.ae]
A 5-year-old girl was admitted with pallor, hypopigmented sparse hair, tongue ulcers, atrophic nail changes, hypoplastic anemia and bilateral exudative retinopathy. A diagnosis of Revesz syndrome was made. [ncbi.nlm.nih.gov]
Definition A disease characterized by bone marrow hypoplasia, nail dystrophy, fine sparse hair, fine reticulate skin pigmentation, oral leukoplakia, bilateral exudative retinopathy, cerebellar hypoplasia, and growth retardation. [uniprot.org]
- Sparse Hair
【關鍵詞】 revesz syndrome retinitis pigmentosa retinal detachment bone marrow failure syndromes revesz syndrome is a rare congenital disorder characterized by intrauterine growth retardation, fine sparse hair, reticulate skin pigmentation, bone marrow failure [doc.qkzz.net]
Other features of this syndrome include intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia because of cerebellar hypoplasia, cerebral calcifications, extensor hypertonia, and progressive psychomotor retardation [cags.org.ae]
A 5-year-old girl was admitted with pallor, hypopigmented sparse hair, tongue ulcers, atrophic nail changes, hypoplastic anemia and bilateral exudative retinopathy. A diagnosis of Revesz syndrome was made. [ncbi.nlm.nih.gov]
Definition A disease characterized by bone marrow hypoplasia, nail dystrophy, fine sparse hair, fine reticulate skin pigmentation, oral leukoplakia, bilateral exudative retinopathy, cerebellar hypoplasia, and growth retardation. [uniprot.org]
- Purpura
/ Eczematid-like purpura of Doucas and Kapetanakis Lichen aureus Angioma serpiginosum Hemosiderin hyperpigmentation Other metals Argyria Chrysiasis Arsenic poisoning Lead poisoning Titanium metallic discoloration Other Carotenosis Tar melanosis Dyschromia [en.wikipedia.org]
A 2-year-old girl presented with thrombocytopenic purpura. [scienceopen.com]
Owing to the pancytopenia, vitreous hemorrhage, and thrombocytopenic purpura, the patient was referred to a pediatric hematologist. In the subsequent months, pancytopenia was persistent. [scielo.br]
EPAS1 EPB42 EPOR G6PD GIF HBA1 HBA2 HBB HBD HFE KIF23 KLF1 LPIN2 RPL11 RPL35A RPL5 RPS10 RPS17 RPS19 RPS24 RPS26 RPS7 SEC23B SH2B3 SPTA1 SPTB BID02: Platelets, Coagulation (17 Genes) Antithrombin III deficiency, Congenital thrombotic thrombocytopenic purpura [bbrauncegat.com]
- Alopecia
Contractures Dwarfism Mental Retardation Alopecia Epilepsy Oligophrenia Syndrome of Moynahan Alopecia, Epilepsy, Pyorrhea, Mental Subnormality Alopecia, Neurologic Defects, and Endocrinopathy Syndrome Alopecia-Mental Retardation Syndrome 1 Alopecia-Mental [rgd.mcw.edu]
Dermatologic anomalies include: pectoral and axillary alopecia, absence of sweat glands and anhidrosis (9). [medichub.ro]
NFKBIA STAT1 TBK1 TICAM1 TIRAP TLR3 TMC6 TMC8 TRAF3 TRAF3IP2 UNC93B1 BID13: Combined immunodeficiencies (60 Genes) Hay-Wells syndrome (ankyloblepharon-ectodermal dysplasia-clefting syndrome), 22q11.2 deletion syndrome, Activated PIK3-delta syndrome, Alopecia [bbrauncegat.com]
Brown AC, Crounse RG, Winkelmann RK: Generalized hair-follicle hamartoma, associated with alopecia, aminoaciduria, and myasthenia gravis. Arch Dermatol 1969;99: 478–493. Rahman SB, Bhawan J: Lentigo. Int J Dermatol 1996;35:229–239. [karger.com]
[…] mouth) One feature of the classic triad plus two or more of the following [ Vulliamy et al 2006 ]: Epiphora (excessive watering of the eye[s]) Blepharitis (inflammation of the eyelids, often due to epiphora) Abnormal eyelashes Prematurely gray hair Alopecia [ncbi.nlm.nih.gov]
- Petechiae
Dermatological examination revealed petechiae in both legs and arms (figure 1). Figure 1 A – Hematoma of the left leg; B – Petechiae on the right arm Screening for HIV I/II, toxoplasmosis, syphilis, and cytomegalovirus was negative. [scielo.br]
Artículo en Inglés | IMSEAR | ID: sea-39464 RESUMEN The authors describe a Thai newborn boy who was presented with petechiae, hepatosplenomegaly and pancytopenia at birth caused by congenital HIV infection. [search.bvsalud.org]
Bruising, small red spots on the skin (petechiae), paleness of the skin (pallor) and frequent infections may be the first signs of bone marrow failure. The specific symptoms and progression of the disorder vary from case to case. [rarediseases.org]
Psychiatrical
- Suggestibility
SUGGESTED PROGRAMMATIC ASSESSMENT* Suggested MER for evaluation: • Clinical history and examination that describes the diagnostic features of the impairment; • Laboratory reports documenting hemoglobin levels and electrophoresis (rule out other hematologic [secure.ssa.gov]
Next article. 19 Jan Griscelli and Prunieras initially described Griscelli syndrome, or partial albinism with immunodeficiency, in Griscelli worked at Hospital. 19 Jun It has been suggested that Elejalde syndrome is the same disease entity as Griscelli [maurershapi.pro]
Mutations in the same gene have also been found in the autosomal dominant form of dyskeratosis congenita (613990) suggesting that the two disorders, if distinct, are allelic. [disorders.eyes.arizona.edu]
Although these findings suggested an autoimmune disease, the symptoms did not respond to immunotherapy. [link.springer.com]
- Psychomotor Retardation
Other features of this syndrome include intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia because of cerebellar hypoplasia, cerebral calcifications, extensor hypertonia, and progressive psychomotor retardation [cags.org.ae]
fine sparse hair, reticulate skin pigmentation, bone marrow failure, cerebral calcification, cerebellar hypoplasia and psychomotor retardation. [doaj.org]
Neurologic
- Cerebral Calcification
Other features of this syndrome include intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia because of cerebellar hypoplasia, cerebral calcifications, extensor hypertonia, and progressive psychomotor retardation [cags.org.ae]
Regarding the neurological findings (hypoplasia and multiple cerebral calcifications), delayed neuropsychomotor development is a common feature in most patients with Revesz syndrome ( 3, 5 ). [scielo.br]
calcification, cerebellar hypoplasia and psychomotor retardation. [doaj.org]
- Delayed Milestone
milestones, Delayed development, Psychomotor development failure, Mental and motor retardation, Psychomotor delay, Delayed psychomotor development [more] A delay in the achievement of motor or mental milestones in the domains of development of a child [rarediseases.oscar.ncsu.edu]
Workup
The diagnosis of Revesz syndrome is reached via a combination of patient history, clinical findings, laboratory results, and genetic testing. It is important that the correct diagnosis of RS be made early, as the risk of developing malignancies, in those affected by the condition, is significant. Moreover, the aforementioned individuals may require and benefit from urgent treatment.
Molecular and genetic studies should be carried out to establish the presence of gene mutations indicative of RS, as well as abnormal telomere lengths [7]. Possible laboratory methods include PCR (polymerase chain reaction), Southern blot, flow cytometry, and fluorescence in situ hybridization (FISH) with immunostaining, [8] [9].
It has been observed that up to half of patients with DC have no observable genetic mutations. The possibility of the syndrome in such patients cannot be ruled out, however, as a diagnosis can be made based on the presence of clinical features consistent with the disease, in addition to molecular studies revealing short telomeres [10].
In older individuals, DC may present with increasingly diverse symptoms that may deviate from the common presentation [11]. The criteria for testing patients for DC or RS may depend on the protocol of a given health facility.
Serum
- Leukopenia
Investigation revealed anemia, leukopenia, and a platelet count of 30.000/µL. Owing to the pancytopenia, vitreous hemorrhage, and thrombocytopenic purpura, the patient was referred to a pediatric hematologist. [scielo.br]
Blood count and peripheral smear findings revealed anaemia in 40[100%], leukopenia in 17 [42.5%] and thrombocytopenia in 36 [90%] patients. Bicytopenia was present in 18 [45%] and pancytopenia in 17 [42.5%] patients. [search.bvsalud.org]
Patient 3 A Caucasian female, with an unremarkable family history, was first noted to have leukopenia, macrocytic anemia, and thrombocytopenia at 21 months of age (WBC 3,600/μl, ANC 1,800/μl, hemoglobin 10.1 gm/dl, MCV 100 fl, and platelets 31,000/μl) [ncbi.nlm.nih.gov]
Individuals with low white blood cell counts (leukopenia) have an increased risk of contracting bacterial and fungal infections. [rarediseases.org]
Treatment
TREATMENT Treatment for this disorder is symptom specific and may require a multidisciplinary team of specialists. The treatment team would likely consist of a pediatrician, ophthalmologist, hematologist, dermatologist, and neurologist. [secure.ssa.gov]
TL;DR: The principles of telomere length maintenance are described, and a current appraisal of the diagnosis, disease manifestations, treatment options, and molecular genetics of DC and related TBDs is provided. ...read moreread less Abstract: Dyskeratosis [typeset.io]
The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]
It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice. [uniprot.org]
Prognosis
The prognosis is guarded, primarily as a result of bone marrow failure. Infections, liver failure, and lung failure are among the more serious problems. Lifelong monitoring for cancer and systemic disease are important. [disorders.eyes.arizona.edu]
Prognosis - Revesz syndrome Not supplied. Treatment - Revesz syndrome Not supplied. Resources - Revesz syndrome Not supplied. [checkorphan.org]
The overall prognosis for individuals with this disease is guarded, primarily as a result of bone marrow failure, infections, liver failure and lung failure. [secure.ssa.gov]
What is the Prognosis of Dyskeratosis Congenita? (Outcomes/Resolutions) The prognosis of Dyskeratosis Congenita depends on the severity of the signs and symptoms. [dovemed.com]
Etiology
Synonyms Retinopathy-anemia-central nervous system anomalies syndrome Revesz-DeBuse syndrome Dyskeratosis congenita with bilateral exudative retinopathy Name in a foreign language - Inheritance Autosomal dominant CONTENT INFORMATION Textual description Etiology [retkebolesti.com]
General pathology > Genetic and developmental anomalies > Revesz syndrome MIM.268130 Tuesday 26 February 2008 Etiology TINF2 germline mutations in Revesz syndrome References Kajtar, P.; Mehes, K. : Bilateral Coats retinopathy associated with aplastic [humpath.com]
The etiology of this disorder is uncertain. In severe cases, the proximal femur, femoral head and neck, and acetabulum are absent. [radiopaedia.org]
(Etiology) Hoyeraal-Hreidarsson Syndrome is caused by mutations in the DCK1 gene (Xq28), encoding the nucleolar proteindyskerin which interacts with the human telomerase RNA complex Mutations in other genes involved in telomere maintenance may be associated [dovemed.com]
Etiology Best Pract Res Clin Haematol 2021 Jun;34(2):101282. Epub 2021 Jul 1 doi: 10.1016/j.beha.2021.101282. PMID: 34404536 Niewisch MR, Savage SA Expert Rev Hematol 2019 Dec;12(12):1037-1052. Epub 2019 Sep 10 doi: 10.1080/17474086.2019.1662720. [ncbi.nlm.nih.gov]
Epidemiology
Dyskeratosis congenita with bilateral exudative retinopathy Name in a foreign language - Inheritance Autosomal dominant CONTENT INFORMATION Textual description Etiology Forecast Differential diagnosis Treatment Diagnostic methods Antenatal diagnosis Epidemiology [retkebolesti.com]
Diagnosis Epidemiology Revesz syndrome has so far been observed only in children. There is not much information about the disease because of its low frequency in general population and under reporting of cases. [owlapps.net]
Epidemiology Revesz syndrome has been observed only in children. [wiki30.com]
(October 2017) Epidemiology[edit] Revesz syndrome has so far been observed only in children. There is not much information about the disease because of its low frequency in general population and under reporting of cases. [en.wikipedia.org]
Relevant External Links for TINF2 Genetic Association Database (GAD) TINF2 Human Genome Epidemiology (HuGE) Navigator TINF2 Atlas of Genetics and Cytogenetics in Oncology and Haematology: TINF2 No data available for Genatlas for TINF2 Gene TIN2, a new [genecards.org]
Pathophysiology
Nathan and Oski’s is the only comprehensive product on the market that relates pathophysiology in such depth to hematologic and oncologic diseases affecting children. [books.google.com]
We report ophthalmic findings in twins with Revesz syndrome due to a previously unreported mutation in TINF2 and propose that phenotypic and molecular overlaps between DKC spectrum disorders and pediatric retinal vasculopathies may reflect a shared pathophysiologic [ncbi.nlm.nih.gov]
Pathophysiology The pathophysiology of Elejalde syndrome is not fully understood. [maurershapi.pro]
His main research interest is in movement disorders, specifically the merging of clinical, electrophysiological and imaging methods to provide insights into the pathophysiology of conditions like dystonia and Parkinson's disease. [books.google.es]
Prevention
In addition to preventing the merger of chromosomes, telomeres are needed to prevent the loss of genetic information each time a cell divides. [sciencedaily.com]
Prevention - Revesz syndrome Not supplied. Diagnosis - Revesz syndrome Not supplied. Prognosis - Revesz syndrome Not supplied. Treatment - Revesz syndrome Not supplied. Resources - Revesz syndrome Not supplied. [checkorphan.org]
Additional information This research was funded by the National Institutes of Health Grant R01 EY014685, the Lew Wasserman Award from Research to Prevent Blindness Inc., New York, NY, an unrestricted departmental grant from Research to Prevent Blindness [tandfonline.com]
The treatments measures may include the following: Use of moisturizing creams to prevent damage to the skin Good dental hygiene to help prevent early tooth loss. [dovemed.com]
References
- Savage SA, Giri N, Baerlocher GM, Orr N, Lansdorp PM, Alter BP. TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. Am J Hum Genet. 2008;82(2):501–509.
- Revesz T, Fletcher S, al-Gazali LI, DeBuse P. Bilateral retinopathy, aplastic anaemia, and central nervous system abnormalities: a new syndrome? J Med Genet. 1992;29(9):673-675.
- Kajtár P, Méhes K. Bilateral coats retinopathy associated with aplastic anaemia and mild dyskeratotic signs. Am J Med Genet. 1994;49(4):374-377.
- Sasa GS, Ribes-Zamora A, Nelson ND, Bertuch AA. Three novel truncating TINF2 mutations causing severe dyskeratosis congenita in early childhood. Clin Genet. 2012;81(5):470-478.
- Riyaz A, Riyaz N, Jayakrishnan MP, Mohamed Shiras PT, Ajith Kumar VT, Ajith BS. Revesz syndrome. Indian J Pediatr. 2007;74(9):862-863.
- Scheinfeld MH, Lui YW, Kolb EA, et al. The neuroradiological findings in a case of Revesz syndrome. Pediatr Radiol. 2007;37(11):1166-1170.
- Savage SA, Alter BP. The role of telomere biology in bone marrow failure and other disorders. Mech Ageing Dev. 2008;129(12):35–47.
- Baird DM. New developments in telomere length analysis. Exp Gerontol.May;40(5):363-368.
- Lin KW, Yan J. The telomere length dynamic and methods of its assessment. J Cell Mol Med. 2005;9(4):977–989.
- Rosenberg P, Giri N, Savage SA, Alter BP. Cancer Epidemiology in the National Cancer Institute Inherited Bone Marrow Failure Syndromes Cohort: First Report. Blood. 2008;112(11):40.
- Dokal I, Vulliamy T, Mason P, Bessler M. Clinical utility gene card for: dyskeratosis congenita. Eur J Hum Genet. 2011;19(11).