Clinical, etiological and therapeutic aspects of Dyskeratosis congenita

  • Rosario Perona Instituto de Investigaciones Biomédicas CSIC/UAM. CIBER de enfermedades raras, IDIPaz, Madrid, España.
  • Leandro Sastre Instituto de Investigaciones Biomédicas CSIC/UAM. CIBER de enfermedades raras, IDIPaz, Madrid, España.
  • Michele Callea Unit of Dentistry, Bambino Gesù Children’s Hospital, IRCSS, Rome, Italy.
  • Francisco Cammarata-Scalisi Unidad de Genética Médica, Departamento de Puericultura y Pediatría, Universidad de Los Andes, Mérida, Venezuela.
Keywords: dyskeratosis congenital, telomeropathies, clinic, etiology, treatment


The Dyskeratosis congenita corresponds to the first genetic entity described among telomeropathies, whose classic form is characterized by presenting the mucocutaneous triad of reticulated skin-lace pigmentation, nail dystrophy and oral leukoplakia. It can also occur with bone marrow failure, hematological and solid tumors, corresponding to the most serious complications. In addition to immunodeficiencies, dental, lung and liver disorders and other aspects considered minor. In turn, it presents varied genetic locus heterogeneity, with at least 14 genes involved in the telomere´s shortening, therefore associated with dyskeratosis congenita or similar phenotypes. This review discusses in addition to the clinical characteristics, the various etiological causes, evolution, available therapeutic options, and the differential diagnostic of this entity in order to provide an interdisciplinary and individualized medical evaluation that includes adequate genetic counseling.


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Trotta L, Norberg A, Taskinen M, Béziat V, Degerman S, Wartiovaara-Kautto U, et al. Diagnostics of rare disorders: whole-exome sequencing deciphering locus heterogeneity in telomere biology disorders. Orphanet J Rare Dis. 2018;13:139.

Ratnasamy V, Navaneethakrishnan S, Sirisena ND, Grüning NM, Brandau O, Thirunavukarasu K, et al. Dyskeratosis congenita with a novel genetic variant in the DKC1 gene: a case report. BMC Med Genet. 2018;19:85.

Savage SA. Beginning at the ends: telomeres and human disease. F1000Res. 2018;7. pii: F1000 Faculty Rev-524.

Fernández García MS, Teruya-Feldstein J. The diagnosis and treatment of dyskeratosis congenita: a review. J Blood Med. 2014;5:157-67.

Khincha PP, Bertuch AA, Gadalla SM, Giri N, Alter BP, Savage SA. Similar telomere attrition rates in androgen-treated and untreated patients with dyskeratosis congenita. Blood Adv. 2018;2:1243-9.

Olivieri C, Mondino A, Chinello M, Risso A, Finale E, Lanciotti M, et al. Clinical heterogeneity in a family with DKC1 mutation, dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome in first cousins. Pediatr Rep. 2017;9:7301.

Ungar RA, Giri N, Pao M, Khincha PP, Zhou W, Alter BP, et al. Complex phenotype of dyskeratosis congenita and mood dysregulation with novel homozygous RTEL1 and TPH1 variants. Am J Med Genet A. 2018;176:1432-7.

Bongiorno M, Rivard S, Hammer D, Kentosh J. Malignant transformation of oral leukoplakia in a patient with dyskeratosis congenita. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;124:e239-42.

Perona R, Machado-Pinilla R, Manguan C, Carrillo J. Telomerase deficiency and cancer susceptibility syndromes. Clin Transl Oncol. 2009;11:711-4.

Carrillo J, Martínez P, Solera J, Moratilla C, González A, Manguán-García C, et al. High resolution melting analysis for the identification of novel mutations in DKC1 and TERT genes in patients with dyskeratosis congenita. Blood Cells Mol Dis. 2012;49:140-6.

Zhang J, Li M, Yao Z. Updated review of genetic reticulate pigmentary disorders. Br J Dermatol. 2017;177:945-59.

Iarriccio L, Manguán-García C, Pintado-Berninches L, Mancheño JM, Molina A, Perona R, et al. GSE4, a small dyskerin- and GSE24.2-related peptide, induces telomerase activity, cell proliferation and reduces DNA damage, oxidative stress and cell Senescence in dyskerin mutant cells. PLoS One. 2015 Nov 16;10(11):e0142980.

Manguan-Garcia C, Pintado-Berninches L, Carrillo J, Machado-Pinilla R, Sastre L, Pérez-Quilis C, et al. Expression of the genetic suppressor element 24.2 (GSE24.2) decreases DNA damage and oxidative stress in X-linked dyskeratosis congenita cells. PLoS One. 2014;9:e101424.

Machado-Pinilla R1, Sánchez-Pérez I, Murguía JR, Sastre L, Perona R. A dyskerin motif reactivates telomerase activity in X-linked dyskeratosis congenita and in telomerase-deficient human cells. Blood. 2008;111:2606-14.

Bär C, Povedano JM, Serrano R, Benitez-Buelga C, Popkes M, Formentini I, et al. Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia. Blood. 2016;127:1770-9.

Penmatsa C, Jampanapalli SR, Bezawada S, Birapu UK, Radharapu VK. Zinsser-Cole-Engman syndrome: A rare case report. J Clin Diagn Res. 2016;10:ZD07-9.

McElnea EM, van der Spek N, Smith O, Fitzsimon S, Patel CK, O'Marcaigh A. Revesz syndrome masquerading as bilateral cicatricial retinopathy of prematurity. J AAPOS. 2013;17:634-6.

Romaniello R, Arrigoni F, Citterio A, Tonelli A, Sforzini C, Rizzari C, et al. Cerebroretinal microangiopathy with calcifications and cysts associated with CTC1 and NDP mutations. J Child Neurol. 2013;28(12):1702-8.

Gu P, Jia S, Takasugi T, Smith E, Nandakumar J, Hendrickson E, et al. CTC1-STN1 coordinates G- and C-strand synthesis to regulate telomere length. Aging Cell. 2018:e12783.

Garofola C, Gross GP. Dyskeratosis Congenita. Source Stat Pearls. Treasure Island (FL): Stat Pearls Publishing; 2018.

Belligni EF, Dokal I, Hennekam RC. Prenatal and postnatal growth retardation, microcephaly, developmental delay, and pigmentation abnormalities: Naegeli syndrome, dyskeratosis congenita, poikiloderma Clericuzio type, or separate entity? Eur J Med Genet. 2011;54:231-5.

Dehmel M, Brenner S, Suttorp M, Hahn G, Schützle H, Dinger J, et al. Novel mutation in the DKC1 gene: neonatal Hoyeraal-Hreidarsson syndrome as a rare differential diagnosis in pontocerebellar hypoplasia, primary microcephaly, and progressive bone marrow failure. Neuropediatrics. 2016;47:182-6.

Anwar MI, Rashid A, Ghafoor R, Tahir M, Rao SU, Mir F. Kindler's syndrome: a report of five cases in a family. J Coll Physicians Surg Pak. 2014;24:763-5.

Mostefai R, Morice-Picard F, Boralevi F, Sautarel M, Lacombe D, Stasia MJ, et al. Poikiloderma with neutropenia, Clericuzio type, in a family from Morocco. Am J Med Genet A. 2008;146A:2762-9.

How to Cite
Perona R, Sastre L, Callea M, Cammarata-Scalisi F. Clinical, etiological and therapeutic aspects of Dyskeratosis congenita. Rev Peru Investig Salud [Internet]. 31Mar.2020 [cited 27Sep.2020];4(2):77-2. Available from:
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