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].

• 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]

• Pallor

  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]

  India2 Department of Dermatology, Medical College, Calicut, Kerala, India3 Comtrust Eye Hospital, Calicut, Kerala, IndiaDate of Submission 29-Dec-2006Date of Acceptance 29-Mar-2007Riyaz AProfessor of Pediatr 【摘要】 a 5-year-old girl was admitted with pallor [doc.qkzz.net]

  Ajith Clinical Brief First Online: 11 December 2007 Abstract A 5-year-old girl was admitted with pallor, hypopigmented sparse hair, tongue ulcers, atrophic nail changes, hypoplastic anemia and bilateral exudative retinopathy. [doi.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]

• 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]

• 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]

• Tongue Ulcer

  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]

  Medical College, Calicut, Kerala, India3 Comtrust Eye Hospital, Calicut, Kerala, IndiaDate of Submission 29-Dec-2006Date of Acceptance 29-Mar-2007Riyaz AProfessor of Pediatr 【摘要】 a 5-year-old girl was admitted with pallor, hypopigmented sparse hair, tongue [doc.qkzz.net]

  Ajith Clinical Brief First Online: 11 December 2007 Abstract A 5-year-old girl was admitted with pallor, hypopigmented sparse hair, tongue ulcers, atrophic nail changes, hypoplastic anemia and bilateral exudative retinopathy. [doi.org]

  ulcers; • Atrophic nail changes; • Hypolastic anemia; and • Cerebral calcifications. [secure.ssa.gov]

• Oral Ulcers

  ulcers and recurrent lower respiratory tract infections since the age of 3 year. she was the first of twins, born at term by normal delivery with a birth weight of 1920 g. second twin died in utero. on clinical examination she had marked failure to thrive [doc.qkzz.net]

• 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]

  Journal of Pediatric Ophthalmology and Strabismus Images in Pediatric Ophthalmology Mihir G. Trivedi, MS; Poonam J. Rai, MS; Shruti P. Shirwadkar, DNB; Harsha S. Pagad, DNB, FMRF; Nayana A. Potdar, MS, FAICO; Chhaya A. [healio.com]

  Patel and Aengus O'Marcaigh, Revesz syndrome masquerading as bilateral cicatricial retinopathy of prematurity, Journal of American Association for Pediatric Ophthalmology and Strabismus, 17, 6, (634), (2013). [doi.org]

• Retinal Hemorrhage

  A 13-month-old boy with mild hemophilia A presented for strabismus evaluation and was found to have retinal hemorrhages in the right eye, left exotropia, and left total retinal detachment. These findings were attributed to trauma and hemophilia A. [ncbi.nlm.nih.gov]

  Key words: Dyskeratosis congenital/diagnosis; Retinal hemorrhage; Anemia, aplastic; Case reports RESUMO A síndrome de Revesz é uma rara variante de disceratose congênita caracterizada por retinopatia exsudativa bilateral, alterações no segmento anterior [scielo.br]

• Cotton Wool Spots

  He underwent successful bone marrow transplantation, and on subsequent evaluation was found to have retinal hemorrhages, vessel sclerosis, and cotton wool spots in the right eye associated with peripheral retinal nonperfusion. [ncbi.nlm.nih.gov]

• 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]

• 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]

  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]

  Ajith Clinical Brief First Online: 11 December 2007 Abstract A 5-year-old girl was admitted with pallor, hypopigmented sparse hair, tongue ulcers, atrophic nail changes, hypoplastic anemia and bilateral exudative retinopathy. [doi.org]

  Other symptoms include severe aplastic anemia, intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia due to cerebellar hypoplasia, and cerebral calcifications. [en.wikipedia.org]

  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]

• 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]

• Eczema

  Humphreys F, Spencer J, McLaren K, Tidman MJ: An histological and ultrastructural study of the ‘dirty neck’ appearance in atopic eczema. Clin Exp Dermatol 1996;21:17–19. Du Toit MJ, Jordaan HF: Pigmenting pityriasis alba. [karger.com]

  Contractures, Osteoporosis, Cortical Dysplasia, and Cerebellar Atrophy Growth Mental Deficiency Syndrome of Myhre GROWTH RETARDATION, INTELLECTUAL DEVELOPMENTAL DISORDER, HYPOTONIA, AND HEPATOPATHY Growth Retardation, Small and Puffy Hands and Feet, and Eczema [rgd.mcw.edu]

• Sparse Fine Hair

  The original cases included individuals with intracranial calcifications, intrauterine growth retardation, BMF, and sparse, fine hair in addition to nail dystrophy and oral leukoplakia. [ncbi.nlm.nih.gov]

• Pitting Nails

  Nail pitting Pitted nails [ more ] 0001803 Nystagmus Involuntary, rapid, rhythmic eye movements 0000639 Oral leukoplakia Oral white patch 0002745 Progressive neurologic deterioration Worsening neurological symptoms 0002344 Psychomotor retardation 0025356 [rarediseases.info.nih.gov]

• Psychomotor Retardation

  retardation and apparent chromosome instability. [medical-dictionary.thefreedictionary.com]

  retardation. a 5-year-old girl with features of this syndrome is reported. » case report a 5-year-old girl born of nonconsanguineous marriage was brought with history of nonhealing oral ulcers and recurrent lower respiratory tract infections since the [doc.qkzz.net]

• Cerebral Calcification

  Both twins developed bone marrow failure and were found to have cerebellar hypoplasia and widespread cerebral calcifications. [ncbi.nlm.nih.gov]

  Other symptoms include severe aplastic anemia, intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia due to cerebellar hypoplasia, and cerebral calcifications. [en.wikipedia.org]

  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]

  Other symptoms include severe aplastic anemia, intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia because of cerebellar hypoplasia, cerebral calcifications. [checkorphan.org]

  An extremely rare condition (OMIM:268130) characterised by bilateral exudative retinopathy, intrauterine growth retardation, fine sparse hair, reticulated skin pigmentation, ataxia due to cerebellar hypoplasia, cerebral calcifications, extensor hypertonia [medical-dictionary.thefreedictionary.com]

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.

1. 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.
2. 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.
3. Kajtár P, Méhes K. Bilateral coats retinopathy associated with aplastic anaemia and mild dyskeratotic signs. Am J Med Genet. 1994;49(4):374-377.
4. 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.
5. Riyaz A, Riyaz N, Jayakrishnan MP, Mohamed Shiras PT, Ajith Kumar VT, Ajith BS. Revesz syndrome. Indian J Pediatr. 2007;74(9):862-863.
6. Scheinfeld MH, Lui YW, Kolb EA, et al. The neuroradiological findings in a case of Revesz syndrome. Pediatr Radiol. 2007;37(11):1166-1170.
7. Savage SA, Alter BP. The role of telomere biology in bone marrow failure and other disorders. Mech Ageing Dev. 2008;129(12):35–47.
8. Baird DM. New developments in telomere length analysis. Exp Gerontol.May;40(5):363-368.
9. Lin KW, Yan J. The telomere length dynamic and methods of its assessment. J Cell Mol Med. 2005;9(4):977–989.
10. 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.
11. Dokal I, Vulliamy T, Mason P, Bessler M. Clinical utility gene card for: dyskeratosis congenita. Eur J Hum Genet. 2011;19(11).